Painful Osteoarthritis of the Knee
Conditions
Keywords
Osteoarthritis
Brief summary
This is a Phase IIb randomised, double-blind, placebo-controlled, dose-response study in participants with painful osteoarthritis (OA) of the knee. The study will assess the safety and efficacy of multiple doses of MEDI7352 compared to placebo, as well as the pharmacokinetics, pharmacodynamics and immunogenicity of MEDI7352 in participants with moderate to severe chronic pain persistent for 3 months or more not adequately controlled by standard of care treatments.
Interventions
DRUGMEDI7352
Participants will receive SC injection of MEDI7352 as stated in arm description.
OTHERPlacebo
Participants will receive SC injection of placebo as stated in arm description.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All participants will be centrally assigned to randomised IP using an Interactive Response Technology/Randomisation and Trial Supply Management (IRT/RTSM) system. Before the study is initiated, telephone number and call-in directions for IRT and/or log in information and directions for RTSM will be provided to each site. The IRT/RTSM will provide investigator(s) or appropriate study personnel with kit identification number to be allocated to participant at IP dosing visit. Details for this will be described in IRT/RTSM user manual that will be provided to each centre. All participants, investigators, and study personnel involved in conduct of the study will be blinded to treatment assignment. The unblinded study personnel (eg, site pharmacist) will not participate in study procedures or data analysis prior to unblinding of study data to all study-related personnel. Unblinded AstraZeneca personnel who are not otherwise involved in study will prepare data for review and interim analyses.
Intervention model description
This is a Phase IIb, multinational, multicentre, randomised, double-blind, placebo-controlled, dose-response study of MEDI7352 in participants 18 to 80 years of age (inclusive) with moderate-to-severe chronic pain of the knee. The study consists of a screening period of up to 45 days, a 12-week treatment period, and a 24-week follow-up (FU) period. Daily pain scores (as measured on an 11-point numerical rating scale \[NRS\]) recorded at the first screening visit and from Day -7 to Day -1 will be used be used to determine eligibility. Participants will be randomised to one of 4 doses of MEDI7352 or placebo. Each participant will receive 6 doses of MEDI7352 or placebo during the treatment period. After the end-of-treatment (EOT) visit at Week 12, participants will enter the FU period, which comprises 3 clinic visits (Weeks 18, 32, and 36) and 4 FU phone calls (Weeks 15, 21, 24, and 28). All participants who receive investigational product (IP) are expected to complete the FU period.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Participants must understand the nature of the study and must give signed and dated written informed consent prior to the initiation of any study procedures, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2. For participants participating in the optional genetic research, a separate signed and dated optional genetic research ICF must be provided prior to collection of samples for optional genetic research that supports the Genomics Initiative. If a participant declines to participate in the genetic research, this will have no influence on the ability of a participant to participate in the study. 3. The participant should be willing and able to understand and comply with all protocol-specified restrictions and procedures and be able to use an electronic patient-reported outcome (ePRO) device as judged by the investigator. 4. The participant must be considered likely to comply with the study protocol and to have a high probability of completing the study, as judged by the investigator. 5. The participant must be willing and able to discontinue all analgesic therapy with nonsteroidal anti-inflammatory drugs (NSAID) or cyclooxygenase-2 (COX-2) inhibitors from the start of the washout period until the end of the FU period. This includes over-the-counter (OTC) pain medications and topical analgesics that contain an NSAID or COX-2 inhibitor.
Exclusion criteria
1. Requires current treatment with another biologic therapeutic agent, disease-modifying antirheumatic drug (DMARD), or other immunosuppressants. 2. Previously received any form of anti-nerve growth factor (NGF); received anti-tumour necrosis factors (TNFs) including but not limited to golimumab, certolizumab, infliximab, adalimumab, etanercept, or rituximab within 12 months prior to screening, or other biological DMARDs (including but not limited to abatacept, tocilizumab, and tofacitinib), or other immunosuppressants within 6 months prior to screening (with the exception of inhaled or topical corticosteroids). 3. Currently receiving strong opioids for any indication. 4. Participation in another clinical study with an IP or device within 60 days or 5 half-lives, whichever is longer, prior to screening. 5. Plasma donation within 28 days of screening or any blood donation or blood loss \> 500 mL within 2 months of screening. 6. Previous allogeneic bone marrow or stem cell transplant. 7. Received nonleukocyte-depleted whole blood transfusion within 120 days of the genetic research sample collection, if participating in the optional genetic research. 8. Involvement in the planning and/or conduct of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12 | Baseline (Day -7 to Day -1, inclusive) through Week 12 | Change from baseline in weekly average of daily NRS pain score to Week 12 is reported. The NRS is an 11-point Likert scale used to assess pain, where participants were asked to describe their average pain in the target knee by identifying a number from 0 = no pain to 10 = most severe pain imaginable over the previous 24 hours. This was recorded on a daily basis at approximately the same time every morning via electronic patient recorded outcome (ePRO) diary. A two-step multiple imputation procedure was used to address missing post-baseline scores. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in WOMAC Physical Function Subscale to Week 12 | Week 0 (Day 1; baseline) through Week 12 | The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC physical function (PF) subscale consists of 17 questions assessing the participant's difficulty in performing activities of daily living due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC PF subscale score is calculated as the mean score from all 17 questions, where higher scores represent worse function. Change from baseline in WOMAC physical function to Week 12 is reported. A two-step multiple imputation procedure was used to address missing post-baseline scores. |
| Change From Baseline in Patient's Global Assessment (PGA) of OA to Week 12 | Week 0 (Day 1; baseline) through Week 12 | The PGA of OA was a 5-point Likert scale used to assess symptoms and activity impairment due to OA of the knee. Participants were asked to identify a number from 1 = very good (asymptomatic and no limitation to normal activities) to 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities) based on the question Considering all the ways that OA of the knee affects you, how are you feeling today?. Change from baseline in PGA of OA to Week 12 is reported. A two-step multiple imputation procedure was used to address missing post-baseline scores. |
| Change From Baseline in WOMAC Pain Subscale Over Time | Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126) | The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC pain subscale consists of 5 questions assessing the participant's pain due to OA in the target knee. Each question was scored on an NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 5 questions, where higher scores represent higher pain. Change from baseline in WOMAC pain subscale to Weeks 2, 4,6, 8, 10, and 18 is reported. |
| Change From Baseline in WOMAC PF Subscale Over Time | Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126) | The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC PF subscale consists of 17 questions assessing the participant's difficulty in performing activities of daily living due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC PF subscale score is calculated as the mean score from all 17 questions, where higher scores represent worse function. Change from baseline in WOMAC physical function to Weeks 2, 4, 6, 8, 10, and 18 is reported. |
| Change From Baseline in WOMAC Overall Score Over Time | Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), and 18 (Day 126) | The WOMAC overall score consisted of all 24 questions reported in the WOMAC questionnaire to assess: i) pain subscale, ii) PF subscale and iii) stiffness subscale. WOMAC overall score was calculated as the mean score from all 24 questions each scored on a Likert scale from 0 to 10 where higher scores represent worse outcome. Change from baseline in weekly average of WOMAC overall score to Weeks 2, 4, 6, 8, 10, 12, and 18 is reported. |
| Change From Baseline in WOMAC Stiffness Scores Over Time | Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), and 18 (Day 126) | The WOMAC stiffness function subscale consists of 2 questions assessing stiffness due to OA in the target knee. Stiffness is defined as a sensation of decreased ease of movement in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC stiffness function subscale score is calculated as the mean score from the 2 questions, where higher scores represent higher stiffness. Change from baseline in WOMAC stiffness score to Weeks 2, 4, 6, 8, 10, 12, and 18 is reported. |
| Change From Baseline in PGA of OA Over Time | Baseline, Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 10 (Day 70), and 18 (Day 126) | The PGA of OA was a 5-point Likert scale used to assess symptoms and activity impairment due to OA of the knee. Participants were asked to identify a number from 1 = very good (asymptomatic and no limitation to normal activities) to 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities) based on the question Considering all the ways that OA of the knee affects you, how are you feeling today?. Change from baseline in PGA of OA to Weeks 2, 4, 8, 10, and 18 is reported. |
| Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126) | The OMERACT-OARSI responder index is calculated from the WOMAC Pain subscale, the WOMAC Physical Function Subscale and the PGA of OA. A participant is classified as a responder if: 1. \>= 2-point absolute change from Baseline to Week X or a \>= 50% improvement is reported in the WOMAC Pain or the PF subscales; 2. At least 2 of the following 3 conditions are true: \>= 1-point absolute change from Baseline to Week X or \>= 20% improvement is reported in the WOMAC Pain subscale, \>= 1-point absolute change from Baseline to Week X or \>= 20% improvement is reported in the WOMAC PF subscale or \>= 1-point absolute change from Baseline to Week X is reported in the PGA of OA. Percentage of responder participants are reported. |
| Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126) | The PGA of OA was a 5-point Likert scale used to assess symptoms and activity impairment due to OA of the knee. Participants were asked to identify a number from 1 = very good (asymptomatic and no limitation to normal activities) to 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities) based on the question Considering all the ways that OA of the knee affects you, how are you feeling today?. Percentage of participants with improvement of \>= 2 points in PGA of OA at Weeks 2, 4, 8, 12, and 18 is reported. |
| Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Baseline (Day -7 to Day -1, inclusive), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126) | The NRS is an 11-point Likert scale used to assess pain, where participants were asked to describe their average pain in the target knee by identifying a number from 0 = no pain to 10 = most severe pain imaginable over the previous 24 hours. This will be recorded on a daily basis at approximately the same time every morning via ePRO diary. Change from baseline in weekly average of daily NRS to Weeks 2, 4, 6, 8, 10, and 18 is reported. |
| Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | Baseline (Day -7 to Day -1, inclusive), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126) | The NRS is an 11-point Likert scale used to assess pain, where participants were asked to describe their average pain in the target knee by identifying a number from 0 = no pain to 10 = most severe pain imaginable over the previous 24 hours. This will be recorded on a daily basis at approximately the same time every morning via ePRO diary. Percentage of participants with \>= 30% and \>= 50% reductions in weekly average of daily NRS pain score are reported. |
| Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126) | The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC pain subscale consists of 5 questions assessing the participant's pain due to OA in the target knee. Each question was scored on an NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 5 questions, where higher scores represent higher pain. Percentage of participants with \>= 30% and \>= 50% reductions in WOMAC pain subscale score over time are reported. |
| Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126) | The WOMAC PF subscale consists of 17 questions assessing the participant's difficulty in performing activities of daily living due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC PF subscale score is calculated as the mean score from all 17 questions, where higher scores represent worse function. Percentage of participants with \>= 30% and \>= 50% reductions in WOMAC physical function subscale over time are reported. |
| Serum Concentration of MEDI7352 | Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224 | Serum concentration of MEDI7352 is reported. |
| Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale to Week 12 | Week 0 (Day 1; baseline) through Week 12 | The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC pain subscale consists of 5 questions assessing the participant's pain due to osteoarthritis (OA) in the target knee. Each question was scored on a NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 5 questions, where higher scores represent higher pain. Change from baseline in WOMAC pain subscale to Week 12 is reported. A two-step multiple imputation procedure was used to address missing post-baseline scores. |
| ADA Titre in Participants Who Were ADA Positive at Baseline and/or Post-baseline | Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224 | The ADA titre in participants who were ADA positive at baseline and/or post-baseline is reported. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Day 1 through 41 weeks (maximum observed duration) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. |
| Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs | Day 1 through 41 weeks (maximum observed duration) | Number of participants with clinically significant findings in physical examination reported as TEAE are reported. A physical examination included assessments of general appearance, skin, head and neck, examination of the oral cavity for any lesions, lymph nodes, thyroid, abdomen (bowel sounds, liver, and spleen palpation), back (including costovertebral angle tenderness), musculoskeletal/extremities, cardiovascular, and respiratory systems. |
| Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Baseline (Day -45 to Day -1), Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), 18 (Day 126), 28 (Day 168), 32 (Day 224), and 36 (Day 252) | Number of participants with clinically significant abnormal findings in neurological examination is reported. The neurological examination included assessment of mental status, cranial nerves, motor examination (muscle strength and tone), upper and lower extremity deep tendon reflexes, plantar responses, sensory system examination, coordination, and gait. |
| Total Neuropathy Score-Nurse (TNSn) Over Time | Baseline (Day -45 to Day -1), Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), 28 (Day 196), and 32 (Day 224) | The TNSn, is a semiquantitative clinical assessment of peripheral nervous system function. The TNSn assessment is collected as scores of motor symptom, autonomic symptom, pin sensibility, sensory symptom, and vibration sensibility score. Each neuropathy item is scored on a 0 to 4 scale with total score ranging from 0 to 20. Higher total scores correlate with more severe neuropathy. |
| Change From Baseline in Weight (kg) to Week 12 | Baseline (Day -45 to -1) and Week 12 | Change from baseline in weight (kg) to Week 12 is reported. |
| Number of Participants With Abnormal Vital Signs Reported as TEAEs | Day 1 through 41 weeks (maximum observed duration) | Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormalfinding in the vital sign parameters (body temperature, supine and standing blood pressure, pulse rate, and respiratory rate). |
| Change From Baseline in Survey of Autonomic Symptoms (SAS) Total Impact Score | Baseline (Day 1; Week 0) and Day 252 (Week 36) | The SAS is an instrument that measures autonomic symptoms used for assessing autonomic neuropathies in clinical trials. The SAS scale evaluates the presence of symptoms and the degree of severity. The SAS consists of 11 questions in women and 12 questions in men. Each question has a Yes or No answer to symptoms occurring 6 months prior to investigational product (IP) administration. Questions answered with Yes are further rated by asking the participant how much each symptom is bothering him or her. Each answer is scored on a scale from 1 to 5 where 1 = not at all and 5 = a lot, and a total symptom impact score is determined. The SAS total impact score is the total of the scores from each question (11 for women and 12 for men). The minimum score is 0 and the maximum is 55 for women and 60 for men. A higher score indicates worse autonomic dysfunction. |
| Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 8 (Day 56), 10 (Day 70), 12 (Day 84), 28 (Day 168), and 32 (Day 224) | Number of participants with clinically significant abnormal ECGs are reported. |
| Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Day 1 through 41 weeks (maximum observed duration) | Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. |
| Change From Baseline in C-reactive Protein Level to Week 12 | Baseline (Day -7 to -1, inclusive) and Week 12 | Change from baseline in C-reactive protein level to Week 12 is reported. |
| Number of Participants With Injection Site Reactions | Day 1 through 41 weeks (maximum observed duration) | Number of participants with injection site reactions are reported. |
| Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints | Baseline (Day -45 to -1) and Week 32 | Number of participants with abnormal X-ray and/or MRI of large joints is reported. |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224 | Number of participants with ADA to MEDI7352 are reported. Treatment-induced ADA positive is defined as ADA negative at baseline and positive at least 1 post-baseline ADA assessment. Treatment-boosted ADA positive is defined as ADA positive at baseline, and the baseline titre is boosted by greater than the variability of the assay (commonly 4-fold) at \>= 1 post-baseline timepoint. Persistent positive is defined as ADA negative at baseline and having at least 2 post-baseline ADA positive assessments (with \>= 16 weeks between first and last positive) or ADA positive at last post-baseline assessment. Transiently positive is defined as ADA negative at baseline and at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. |
Countries
Denmark, Estonia, Germany, Poland, Spain, United Kingdom
Participant flow
Recruitment details
The study was conducted at 50 sites in 6 countries (the United Kingdom, Denmark, Estonia, Germany, Poland, and Spain).
Pre-assignment details
A total of 345 participants were randomized, of which 344 participants received at least one dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| MEDl7352 Dose Level 1 Participants received 6 doses of subcutaneous (SC) MEDl7352 Dose Level 1 injection once every 2 weeks (Q2W) during a 12-week parallel-group treatment period. | 70 |
| MEDl7352 Dose Level 2 Participants received 6 doses of SC MEDl7352 Dose Level 2 injection Q2W during a 12-week parallel-group treatment period. | 68 |
| MEDl7352 Dose Level 3 Participants received 6 doses of SC MEDl7352 Dose Level 3 injection Q2W during a 12-week parallel-group treatment period. | 69 |
| MEDl7352 Dose Level 4 Participants received 6 doses of SC MEDl7352 Dose Level 4 injection Q2W during a 12-week parallel-group treatment period. | 68 |
| Placebo Participants received 6 doses of SC placebo injection matched to MEDl7352 Q2W during a 12-week parallel-group treatment period. | 70 |
| Total | 345 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 1 | 3 |
| Overall Study | Withdrawal by Subject | 9 | 3 | 4 | 8 | 6 |
Baseline characteristics
| Characteristic | MEDl7352 Dose Level 1 | MEDl7352 Dose Level 2 | MEDl7352 Dose Level 3 | MEDl7352 Dose Level 4 | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 65.8 Years STANDARD_DEVIATION 7.9 | 63.3 Years STANDARD_DEVIATION 7.73 | 63.8 Years STANDARD_DEVIATION 6.91 | 63.3 Years STANDARD_DEVIATION 7.52 | 62.5 Years STANDARD_DEVIATION 8.03 | 63.7 Years STANDARD_DEVIATION 7.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 69 Participants | 67 Participants | 67 Participants | 67 Participants | 70 Participants | 340 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 69 Participants | 66 Participants | 67 Participants | 65 Participants | 67 Participants | 334 Participants |
| Sex: Female, Male Female | 43 Participants | 51 Participants | 48 Participants | 46 Participants | 42 Participants | 230 Participants |
| Sex: Female, Male Male | 27 Participants | 17 Participants | 21 Participants | 22 Participants | 28 Participants | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 68 | 0 / 69 | 0 / 68 | 0 / 69 |
| other Total, other adverse events | 51 / 70 | 45 / 68 | 54 / 69 | 51 / 68 | 40 / 69 |
| serious Total, serious adverse events | 3 / 70 | 5 / 68 | 3 / 69 | 1 / 68 | 2 / 69 |
Outcome results
Primary
Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12
Change from baseline in weekly average of daily NRS pain score to Week 12 is reported. The NRS is an 11-point Likert scale used to assess pain, where participants were asked to describe their average pain in the target knee by identifying a number from 0 = no pain to 10 = most severe pain imaginable over the previous 24 hours. This was recorded on a daily basis at approximately the same time every morning via electronic patient recorded outcome (ePRO) diary. A two-step multiple imputation procedure was used to address missing post-baseline scores.
Time frame: Baseline (Day -7 to Day -1, inclusive) through Week 12
Population: Full analysis set (FAS) included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12 | -2.19 Unit on a scale | Standard Deviation 2.243 |
| MEDl7352 Dose Level 2 | Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12 | -3.00 Unit on a scale | Standard Deviation 2.342 |
| MEDl7352 Dose Level 3 | Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12 | -2.83 Unit on a scale | Standard Deviation 2.522 |
| MEDl7352 Dose Level 4 | Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12 | -2.81 Unit on a scale | Standard Deviation 2.835 |
| Placebo | Change From Baseline in Weekly Average of Daily Numerical Rating Scale (NRS) Pain Score to Week 12 | -2.35 Unit on a scale | Standard Deviation 2.364 |
p-value: 0.3695% CI: [-0.968, 0.67]ANCOVA
p-value: 0.02995% CI: [-1.619, 0.027]ANCOVA
p-value: 0.02695% CI: [-1.618, 0.009]ANCOVA
p-value: 0.08395% CI: [-1.423, 0.245]ANCOVA
Secondary
ADA Titre in Participants Who Were ADA Positive at Baseline and/or Post-baseline
The ADA titre in participants who were ADA positive at baseline and/or post-baseline is reported.
Time frame: Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224
Population: ADA evaluable participants included all participants in safety analysis set who have non-missing baseline and at least 1 non-missing post-baseline ADA results. Number of participants analyzed (N): number of participants who were ADA positive at baseline and/or post-baseline. Number analyzed (n): participants who had adequate ADA sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDl7352 Dose Level 1 | ADA Titre in Participants Who Were ADA Positive at Baseline and/or Post-baseline | 960.0 Ratio |
| MEDl7352 Dose Level 2 | ADA Titre in Participants Who Were ADA Positive at Baseline and/or Post-baseline | 960.0 Ratio |
| MEDl7352 Dose Level 3 | ADA Titre in Participants Who Were ADA Positive at Baseline and/or Post-baseline | 960.0 Ratio |
| MEDl7352 Dose Level 4 | ADA Titre in Participants Who Were ADA Positive at Baseline and/or Post-baseline | 720.0 Ratio |
| Placebo | ADA Titre in Participants Who Were ADA Positive at Baseline and/or Post-baseline | 240.0 Ratio |
Secondary
Change From Baseline in C-reactive Protein Level to Week 12
Change from baseline in C-reactive protein level to Week 12 is reported.
Time frame: Baseline (Day -7 to -1, inclusive) and Week 12
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated at Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in C-reactive Protein Level to Week 12 | -2.55 mg/L | Standard Deviation 1.975 |
| MEDl7352 Dose Level 2 | Change From Baseline in C-reactive Protein Level to Week 12 | -3.34 mg/L | Standard Deviation 2.004 |
| MEDl7352 Dose Level 3 | Change From Baseline in C-reactive Protein Level to Week 12 | -3.30 mg/L | Standard Deviation 2.422 |
| MEDl7352 Dose Level 4 | Change From Baseline in C-reactive Protein Level to Week 12 | -3.68 mg/L | Standard Deviation 2.313 |
| Placebo | Change From Baseline in C-reactive Protein Level to Week 12 | -2.38 mg/L | Standard Deviation 1.971 |
Secondary
Change From Baseline in Patient's Global Assessment (PGA) of OA to Week 12
The PGA of OA was a 5-point Likert scale used to assess symptoms and activity impairment due to OA of the knee. Participants were asked to identify a number from 1 = very good (asymptomatic and no limitation to normal activities) to 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities) based on the question Considering all the ways that OA of the knee affects you, how are you feeling today?. Change from baseline in PGA of OA to Week 12 is reported. A two-step multiple imputation procedure was used to address missing post-baseline scores.
Time frame: Week 0 (Day 1; baseline) through Week 12
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in Patient's Global Assessment (PGA) of OA to Week 12 | -0.34 Unit on a scale | Standard Deviation 0.933 |
| MEDl7352 Dose Level 2 | Change From Baseline in Patient's Global Assessment (PGA) of OA to Week 12 | -0.72 Unit on a scale | Standard Deviation 1.123 |
| MEDl7352 Dose Level 3 | Change From Baseline in Patient's Global Assessment (PGA) of OA to Week 12 | -0.81 Unit on a scale | Standard Deviation 1.032 |
| MEDl7352 Dose Level 4 | Change From Baseline in Patient's Global Assessment (PGA) of OA to Week 12 | -0.69 Unit on a scale | Standard Deviation 1.377 |
| Placebo | Change From Baseline in Patient's Global Assessment (PGA) of OA to Week 12 | -0.57 Unit on a scale | Standard Deviation 1.003 |
Secondary
Change From Baseline in PGA of OA Over Time
The PGA of OA was a 5-point Likert scale used to assess symptoms and activity impairment due to OA of the knee. Participants were asked to identify a number from 1 = very good (asymptomatic and no limitation to normal activities) to 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities) based on the question Considering all the ways that OA of the knee affects you, how are you feeling today?. Change from baseline in PGA of OA to Weeks 2, 4, 8, 10, and 18 is reported.
Time frame: Baseline, Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 10 (Day 70), and 18 (Day 126)
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants who were evaluable for the specified outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in PGA of OA Over Time | Week 10 | -0.42 Unit on a scale | Standard Deviation 0.723 |
| MEDl7352 Dose Level 1 | Change From Baseline in PGA of OA Over Time | Week 2 | -0.35 Unit on a scale | Standard Deviation 0.812 |
| MEDl7352 Dose Level 1 | Change From Baseline in PGA of OA Over Time | Week 18 | -0.39 Unit on a scale | Standard Deviation 0.655 |
| MEDl7352 Dose Level 1 | Change From Baseline in PGA of OA Over Time | Week 4 | -0.48 Unit on a scale | Standard Deviation 0.738 |
| MEDl7352 Dose Level 1 | Change From Baseline in PGA of OA Over Time | Week 8 | -0.57 Unit on a scale | Standard Deviation 0.91 |
| MEDl7352 Dose Level 2 | Change From Baseline in PGA of OA Over Time | Week 10 | -0.76 Unit on a scale | Standard Deviation 0.922 |
| MEDl7352 Dose Level 2 | Change From Baseline in PGA of OA Over Time | Week 8 | -0.80 Unit on a scale | Standard Deviation 1.026 |
| MEDl7352 Dose Level 2 | Change From Baseline in PGA of OA Over Time | Week 4 | -0.68 Unit on a scale | Standard Deviation 1.066 |
| MEDl7352 Dose Level 2 | Change From Baseline in PGA of OA Over Time | Week 18 | -0.66 Unit on a scale | Standard Deviation 1.022 |
| MEDl7352 Dose Level 2 | Change From Baseline in PGA of OA Over Time | Week 2 | -0.56 Unit on a scale | Standard Deviation 0.917 |
| MEDl7352 Dose Level 3 | Change From Baseline in PGA of OA Over Time | Week 8 | -1.02 Unit on a scale | Standard Deviation 1.09 |
| MEDl7352 Dose Level 3 | Change From Baseline in PGA of OA Over Time | Week 2 | -0.67 Unit on a scale | Standard Deviation 0.933 |
| MEDl7352 Dose Level 3 | Change From Baseline in PGA of OA Over Time | Week 4 | -0.86 Unit on a scale | Standard Deviation 1.043 |
| MEDl7352 Dose Level 3 | Change From Baseline in PGA of OA Over Time | Week 10 | -1.02 Unit on a scale | Standard Deviation 1.01 |
| MEDl7352 Dose Level 3 | Change From Baseline in PGA of OA Over Time | Week 18 | -0.83 Unit on a scale | Standard Deviation 1.117 |
| MEDl7352 Dose Level 4 | Change From Baseline in PGA of OA Over Time | Week 18 | -1.10 Unit on a scale | Standard Deviation 1.294 |
| MEDl7352 Dose Level 4 | Change From Baseline in PGA of OA Over Time | Week 2 | -0.42 Unit on a scale | Standard Deviation 1.059 |
| MEDl7352 Dose Level 4 | Change From Baseline in PGA of OA Over Time | Week 10 | -1.06 Unit on a scale | Standard Deviation 1.295 |
| MEDl7352 Dose Level 4 | Change From Baseline in PGA of OA Over Time | Week 8 | -1.04 Unit on a scale | Standard Deviation 1.098 |
| MEDl7352 Dose Level 4 | Change From Baseline in PGA of OA Over Time | Week 4 | -0.86 Unit on a scale | Standard Deviation 1.106 |
| Placebo | Change From Baseline in PGA of OA Over Time | Week 8 | -0.51 Unit on a scale | Standard Deviation 0.843 |
| Placebo | Change From Baseline in PGA of OA Over Time | Week 10 | -0.67 Unit on a scale | Standard Deviation 0.826 |
| Placebo | Change From Baseline in PGA of OA Over Time | Week 2 | -0.37 Unit on a scale | Standard Deviation 0.698 |
| Placebo | Change From Baseline in PGA of OA Over Time | Week 18 | -0.56 Unit on a scale | Standard Deviation 0.7 |
| Placebo | Change From Baseline in PGA of OA Over Time | Week 4 | -0.48 Unit on a scale | Standard Deviation 0.792 |
Secondary
Change From Baseline in Survey of Autonomic Symptoms (SAS) Total Impact Score
The SAS is an instrument that measures autonomic symptoms used for assessing autonomic neuropathies in clinical trials. The SAS scale evaluates the presence of symptoms and the degree of severity. The SAS consists of 11 questions in women and 12 questions in men. Each question has a Yes or No answer to symptoms occurring 6 months prior to investigational product (IP) administration. Questions answered with Yes are further rated by asking the participant how much each symptom is bothering him or her. Each answer is scored on a scale from 1 to 5 where 1 = not at all and 5 = a lot, and a total symptom impact score is determined. The SAS total impact score is the total of the scores from each question (11 for women and 12 for men). The minimum score is 0 and the maximum is 55 for women and 60 for men. A higher score indicates worse autonomic dysfunction.
Time frame: Baseline (Day 1; Week 0) and Day 252 (Week 36)
Population: Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Number of participants analyzed (N) denotes the number of participants who were evaluable for the specified outcome measure. Number analyzed (n) denotes those participants who had adequate SAS impact score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in Survey of Autonomic Symptoms (SAS) Total Impact Score | -1.5 Unit on a scale | Standard Deviation 4.78 |
| MEDl7352 Dose Level 2 | Change From Baseline in Survey of Autonomic Symptoms (SAS) Total Impact Score | -1.1 Unit on a scale | Standard Deviation 4.63 |
| MEDl7352 Dose Level 3 | Change From Baseline in Survey of Autonomic Symptoms (SAS) Total Impact Score | -0.9 Unit on a scale | Standard Deviation 4.13 |
| MEDl7352 Dose Level 4 | Change From Baseline in Survey of Autonomic Symptoms (SAS) Total Impact Score | -1.6 Unit on a scale | Standard Deviation 4.62 |
| Placebo | Change From Baseline in Survey of Autonomic Symptoms (SAS) Total Impact Score | -0.8 Unit on a scale | Standard Deviation 3.5 |
Secondary
Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time
The NRS is an 11-point Likert scale used to assess pain, where participants were asked to describe their average pain in the target knee by identifying a number from 0 = no pain to 10 = most severe pain imaginable over the previous 24 hours. This will be recorded on a daily basis at approximately the same time every morning via ePRO diary. Change from baseline in weekly average of daily NRS to Weeks 2, 4, 6, 8, 10, and 18 is reported.
Time frame: Baseline (Day -7 to Day -1, inclusive), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126)
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 2 | -1.62 Unit on a scale | Standard Deviation 1.704 |
| MEDl7352 Dose Level 1 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 4 | -1.88 Unit on a scale | Standard Deviation 1.653 |
| MEDl7352 Dose Level 1 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 6 | -2.17 Unit on a scale | Standard Deviation 1.687 |
| MEDl7352 Dose Level 1 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 8 | -2.27 Unit on a scale | Standard Deviation 1.736 |
| MEDl7352 Dose Level 1 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 10 | -2.38 Unit on a scale | Standard Deviation 2.001 |
| MEDl7352 Dose Level 1 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 18 | -2.08 Unit on a scale | Standard Deviation 2.12 |
| MEDl7352 Dose Level 2 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 10 | -3.18 Unit on a scale | Standard Deviation 1.93 |
| MEDl7352 Dose Level 2 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 18 | -3.18 Unit on a scale | Standard Deviation 2.237 |
| MEDl7352 Dose Level 2 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 2 | -1.86 Unit on a scale | Standard Deviation 1.949 |
| MEDl7352 Dose Level 2 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 6 | -2.83 Unit on a scale | Standard Deviation 2.248 |
| MEDl7352 Dose Level 2 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 8 | -2.91 Unit on a scale | Standard Deviation 2.084 |
| MEDl7352 Dose Level 2 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 4 | -2.50 Unit on a scale | Standard Deviation 2.163 |
| MEDl7352 Dose Level 3 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 8 | -3.09 Unit on a scale | Standard Deviation 2.205 |
| MEDl7352 Dose Level 3 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 10 | -3.24 Unit on a scale | Standard Deviation 2.294 |
| MEDl7352 Dose Level 3 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 2 | -1.97 Unit on a scale | Standard Deviation 2.012 |
| MEDl7352 Dose Level 3 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 6 | -3.00 Unit on a scale | Standard Deviation 2.192 |
| MEDl7352 Dose Level 3 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 4 | -2.68 Unit on a scale | Standard Deviation 2.177 |
| MEDl7352 Dose Level 3 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 18 | -2.90 Unit on a scale | Standard Deviation 2.157 |
| MEDl7352 Dose Level 4 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 8 | -3.45 Unit on a scale | Standard Deviation 2.365 |
| MEDl7352 Dose Level 4 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 4 | -2.65 Unit on a scale | Standard Deviation 2.333 |
| MEDl7352 Dose Level 4 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 6 | -3.35 Unit on a scale | Standard Deviation 2.498 |
| MEDl7352 Dose Level 4 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 18 | -3.63 Unit on a scale | Standard Deviation 2.383 |
| MEDl7352 Dose Level 4 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 10 | -3.57 Unit on a scale | Standard Deviation 2.274 |
| MEDl7352 Dose Level 4 | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 2 | -2.26 Unit on a scale | Standard Deviation 2.129 |
| Placebo | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 10 | -2.28 Unit on a scale | Standard Deviation 2.047 |
| Placebo | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 6 | -1.97 Unit on a scale | Standard Deviation 2.02 |
| Placebo | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 4 | -1.66 Unit on a scale | Standard Deviation 1.854 |
| Placebo | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 18 | -2.45 Unit on a scale | Standard Deviation 1.969 |
| Placebo | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 8 | -2.18 Unit on a scale | Standard Deviation 2.274 |
| Placebo | Change From Baseline in Weekly Average of Daily NRS Pain Score Over Time | Week 2 | -1.10 Unit on a scale | Standard Deviation 1.811 |
Secondary
Change From Baseline in Weight (kg) to Week 12
Change from baseline in weight (kg) to Week 12 is reported.
Time frame: Baseline (Day -45 to -1) and Week 12
Population: Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Number of participants analyzed (N) denotes the number of participants evaluated at Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in Weight (kg) to Week 12 | -0.25 kg | Standard Deviation 2.048 |
| MEDl7352 Dose Level 2 | Change From Baseline in Weight (kg) to Week 12 | 0.10 kg | Standard Deviation 2.343 |
| MEDl7352 Dose Level 3 | Change From Baseline in Weight (kg) to Week 12 | 0.34 kg | Standard Deviation 1.932 |
| MEDl7352 Dose Level 4 | Change From Baseline in Weight (kg) to Week 12 | -0.03 kg | Standard Deviation 1.864 |
| Placebo | Change From Baseline in Weight (kg) to Week 12 | -0.34 kg | Standard Deviation 2.004 |
Secondary
Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale to Week 12
The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC pain subscale consists of 5 questions assessing the participant's pain due to osteoarthritis (OA) in the target knee. Each question was scored on a NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 5 questions, where higher scores represent higher pain. Change from baseline in WOMAC pain subscale to Week 12 is reported. A two-step multiple imputation procedure was used to address missing post-baseline scores.
Time frame: Week 0 (Day 1; baseline) through Week 12
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale to Week 12 | -1.88 Unit on a scale | Standard Deviation 2.047 |
| MEDl7352 Dose Level 2 | Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale to Week 12 | -2.88 Unit on a scale | Standard Deviation 2.407 |
| MEDl7352 Dose Level 3 | Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale to Week 12 | -2.62 Unit on a scale | Standard Deviation 2.305 |
| MEDl7352 Dose Level 4 | Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale to Week 12 | -2.57 Unit on a scale | Standard Deviation 2.992 |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale to Week 12 | -2.62 Unit on a scale | Standard Deviation 2.558 |
Secondary
Change From Baseline in WOMAC Overall Score Over Time
The WOMAC overall score consisted of all 24 questions reported in the WOMAC questionnaire to assess: i) pain subscale, ii) PF subscale and iii) stiffness subscale. WOMAC overall score was calculated as the mean score from all 24 questions each scored on a Likert scale from 0 to 10 where higher scores represent worse outcome. Change from baseline in weekly average of WOMAC overall score to Weeks 2, 4, 6, 8, 10, 12, and 18 is reported.
Time frame: Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), and 18 (Day 126)
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Overall Score Over Time | Week 2 | -1.11 Unit on a scale | Standard Deviation 1.546 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Overall Score Over Time | Week 18 | -1.68 Unit on a scale | Standard Deviation 2.148 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Overall Score Over Time | Week 12 | -1.82 Unit on a scale | Standard Deviation 1.945 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Overall Score Over Time | Week 6 | -1.85 Unit on a scale | Standard Deviation 1.583 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Overall Score Over Time | Week 4 | -1.66 Unit on a scale | Standard Deviation 1.706 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Overall Score Over Time | Week 8 | -1.75 Unit on a scale | Standard Deviation 1.792 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Overall Score Over Time | Week 10 | -1.86 Unit on a scale | Standard Deviation 1.907 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Overall Score Over Time | Week 10 | -2.94 Unit on a scale | Standard Deviation 1.995 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Overall Score Over Time | Week 8 | -2.85 Unit on a scale | Standard Deviation 1.995 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Overall Score Over Time | Week 4 | -2.14 Unit on a scale | Standard Deviation 1.958 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Overall Score Over Time | Week 2 | -1.71 Unit on a scale | Standard Deviation 1.836 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Overall Score Over Time | Week 12 | -3.00 Unit on a scale | Standard Deviation 2.087 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Overall Score Over Time | Week 6 | -2.54 Unit on a scale | Standard Deviation 1.968 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Overall Score Over Time | Week 18 | -2.78 Unit on a scale | Standard Deviation 2.153 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Overall Score Over Time | Week 8 | -2.69 Unit on a scale | Standard Deviation 1.757 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Overall Score Over Time | Week 2 | -1.58 Unit on a scale | Standard Deviation 1.343 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Overall Score Over Time | Week 4 | -2.25 Unit on a scale | Standard Deviation 1.667 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Overall Score Over Time | Week 6 | -2.52 Unit on a scale | Standard Deviation 1.426 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Overall Score Over Time | Week 10 | -2.72 Unit on a scale | Standard Deviation 1.663 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Overall Score Over Time | Week 12 | -2.76 Unit on a scale | Standard Deviation 1.616 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Overall Score Over Time | Week 18 | -2.46 Unit on a scale | Standard Deviation 1.718 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Overall Score Over Time | Week 6 | -2.79 Unit on a scale | Standard Deviation 1.951 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Overall Score Over Time | Week 10 | -3.35 Unit on a scale | Standard Deviation 1.954 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Overall Score Over Time | Week 4 | -2.45 Unit on a scale | Standard Deviation 2 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Overall Score Over Time | Week 18 | -3.24 Unit on a scale | Standard Deviation 1.784 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Overall Score Over Time | Week 12 | -3.48 Unit on a scale | Standard Deviation 2.121 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Overall Score Over Time | Week 2 | -1.88 Unit on a scale | Standard Deviation 1.735 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Overall Score Over Time | Week 8 | -3.12 Unit on a scale | Standard Deviation 1.822 |
| Placebo | Change From Baseline in WOMAC Overall Score Over Time | Week 6 | -1.98 Unit on a scale | Standard Deviation 1.984 |
| Placebo | Change From Baseline in WOMAC Overall Score Over Time | Week 18 | -2.42 Unit on a scale | Standard Deviation 1.767 |
| Placebo | Change From Baseline in WOMAC Overall Score Over Time | Week 12 | -2.56 Unit on a scale | Standard Deviation 1.956 |
| Placebo | Change From Baseline in WOMAC Overall Score Over Time | Week 10 | -2.43 Unit on a scale | Standard Deviation 2.022 |
| Placebo | Change From Baseline in WOMAC Overall Score Over Time | Week 4 | -1.74 Unit on a scale | Standard Deviation 1.671 |
| Placebo | Change From Baseline in WOMAC Overall Score Over Time | Week 2 | -1.04 Unit on a scale | Standard Deviation 1.695 |
| Placebo | Change From Baseline in WOMAC Overall Score Over Time | Week 8 | -2.19 Unit on a scale | Standard Deviation 2.102 |
Secondary
Change From Baseline in WOMAC Pain Subscale Over Time
The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC pain subscale consists of 5 questions assessing the participant's pain due to OA in the target knee. Each question was scored on an NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 5 questions, where higher scores represent higher pain. Change from baseline in WOMAC pain subscale to Weeks 2, 4,6, 8, 10, and 18 is reported.
Time frame: Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126)
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 10 | -2.14 Unit on a scale | Standard Deviation 1.886 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 18 | -2.00 Unit on a scale | Standard Deviation 2.09 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 4 | -1.62 Unit on a scale | Standard Deviation 1.635 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 8 | -2.01 Unit on a scale | Standard Deviation 1.84 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 6 | -2.01 Unit on a scale | Standard Deviation 1.541 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 2 | -1.32 Unit on a scale | Standard Deviation 1.501 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 4 | -2.33 Unit on a scale | Standard Deviation 2.23 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 10 | -3.22 Unit on a scale | Standard Deviation 2.282 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 18 | -3.02 Unit on a scale | Standard Deviation 2.388 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 2 | -1.79 Unit on a scale | Standard Deviation 1.988 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 6 | -2.76 Unit on a scale | Standard Deviation 2.223 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 8 | -2.96 Unit on a scale | Standard Deviation 2.259 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 18 | -2.61 Unit on a scale | Standard Deviation 2.107 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 4 | -2.41 Unit on a scale | Standard Deviation 1.939 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 8 | -2.91 Unit on a scale | Standard Deviation 1.954 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 6 | -2.73 Unit on a scale | Standard Deviation 1.852 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 10 | -2.89 Unit on a scale | Standard Deviation 2.052 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 2 | -1.58 Unit on a scale | Standard Deviation 1.571 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 18 | -3.50 Unit on a scale | Standard Deviation 1.988 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 6 | -3.07 Unit on a scale | Standard Deviation 2.065 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 4 | -2.60 Unit on a scale | Standard Deviation 2.077 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 8 | -3.33 Unit on a scale | Standard Deviation 1.964 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 10 | -3.54 Unit on a scale | Standard Deviation 2.055 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Pain Subscale Over Time | Week 2 | -1.88 Unit on a scale | Standard Deviation 1.953 |
| Placebo | Change From Baseline in WOMAC Pain Subscale Over Time | Week 10 | -2.89 Unit on a scale | Standard Deviation 2.283 |
| Placebo | Change From Baseline in WOMAC Pain Subscale Over Time | Week 6 | -2.40 Unit on a scale | Standard Deviation 2.114 |
| Placebo | Change From Baseline in WOMAC Pain Subscale Over Time | Week 18 | -2.97 Unit on a scale | Standard Deviation 2.219 |
| Placebo | Change From Baseline in WOMAC Pain Subscale Over Time | Week 2 | -1.30 Unit on a scale | Standard Deviation 1.968 |
| Placebo | Change From Baseline in WOMAC Pain Subscale Over Time | Week 4 | -2.08 Unit on a scale | Standard Deviation 2 |
| Placebo | Change From Baseline in WOMAC Pain Subscale Over Time | Week 8 | -2.56 Unit on a scale | Standard Deviation 2.431 |
Secondary
Change From Baseline in WOMAC PF Subscale Over Time
The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC PF subscale consists of 17 questions assessing the participant's difficulty in performing activities of daily living due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC PF subscale score is calculated as the mean score from all 17 questions, where higher scores represent worse function. Change from baseline in WOMAC physical function to Weeks 2, 4, 6, 8, 10, and 18 is reported.
Time frame: Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), and 18 (Day 126)
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC PF Subscale Over Time | Week 2 | -1.06 Unit on a scale | Standard Deviation 1.621 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC PF Subscale Over Time | Week 4 | -1.59 Unit on a scale | Standard Deviation 1.812 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC PF Subscale Over Time | Week 8 | -1.64 Unit on a scale | Standard Deviation 1.856 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC PF Subscale Over Time | Week 6 | -1.77 Unit on a scale | Standard Deviation 1.67 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC PF Subscale Over Time | Week 10 | -1.74 Unit on a scale | Standard Deviation 1.994 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC PF Subscale Over Time | Week 18 | -1.55 Unit on a scale | Standard Deviation 2.267 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC PF Subscale Over Time | Week 10 | -2.85 Unit on a scale | Standard Deviation 1.944 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC PF Subscale Over Time | Week 6 | -2.43 Unit on a scale | Standard Deviation 1.946 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC PF Subscale Over Time | Week 2 | -1.64 Unit on a scale | Standard Deviation 1.877 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC PF Subscale Over Time | Week 18 | -2.71 Unit on a scale | Standard Deviation 2.141 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC PF Subscale Over Time | Week 8 | -2.82 Unit on a scale | Standard Deviation 1.96 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC PF Subscale Over Time | Week 4 | -2.07 Unit on a scale | Standard Deviation 1.933 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC PF Subscale Over Time | Week 8 | -2.68 Unit on a scale | Standard Deviation 1.792 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC PF Subscale Over Time | Week 10 | -2.65 Unit on a scale | Standard Deviation 1.671 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC PF Subscale Over Time | Week 2 | -1.56 Unit on a scale | Standard Deviation 1.417 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC PF Subscale Over Time | Week 6 | -2.43 Unit on a scale | Standard Deviation 1.436 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC PF Subscale Over Time | Week 4 | -2.20 Unit on a scale | Standard Deviation 1.701 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC PF Subscale Over Time | Week 18 | -2.37 Unit on a scale | Standard Deviation 1.722 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC PF Subscale Over Time | Week 8 | -3.06 Unit on a scale | Standard Deviation 1.858 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC PF Subscale Over Time | Week 4 | -2.39 Unit on a scale | Standard Deviation 2.062 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC PF Subscale Over Time | Week 6 | -2.71 Unit on a scale | Standard Deviation 2.001 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC PF Subscale Over Time | Week 18 | -3.17 Unit on a scale | Standard Deviation 1.812 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC PF Subscale Over Time | Week 10 | -3.30 Unit on a scale | Standard Deviation 1.979 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC PF Subscale Over Time | Week 2 | -1.80 Unit on a scale | Standard Deviation 1.778 |
| Placebo | Change From Baseline in WOMAC PF Subscale Over Time | Week 10 | -2.26 Unit on a scale | Standard Deviation 2.063 |
| Placebo | Change From Baseline in WOMAC PF Subscale Over Time | Week 6 | -1.92 Unit on a scale | Standard Deviation 1.945 |
| Placebo | Change From Baseline in WOMAC PF Subscale Over Time | Week 4 | -1.62 Unit on a scale | Standard Deviation 1.708 |
| Placebo | Change From Baseline in WOMAC PF Subscale Over Time | Week 18 | -2.24 Unit on a scale | Standard Deviation 1.81 |
| Placebo | Change From Baseline in WOMAC PF Subscale Over Time | Week 8 | -2.06 Unit on a scale | Standard Deviation 2.114 |
| Placebo | Change From Baseline in WOMAC PF Subscale Over Time | Week 2 | -0.96 Unit on a scale | Standard Deviation 1.728 |
Secondary
Change From Baseline in WOMAC Physical Function Subscale to Week 12
The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC physical function (PF) subscale consists of 17 questions assessing the participant's difficulty in performing activities of daily living due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC PF subscale score is calculated as the mean score from all 17 questions, where higher scores represent worse function. Change from baseline in WOMAC physical function to Week 12 is reported. A two-step multiple imputation procedure was used to address missing post-baseline scores.
Time frame: Week 0 (Day 1; baseline) through Week 12
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Physical Function Subscale to Week 12 | -1.48 Unit on a scale | Standard Deviation 2.233 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Physical Function Subscale to Week 12 | -2.56 Unit on a scale | Standard Deviation 2.352 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Physical Function Subscale to Week 12 | -2.45 Unit on a scale | Standard Deviation 1.909 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Physical Function Subscale to Week 12 | -2.22 Unit on a scale | Standard Deviation 2.887 |
| Placebo | Change From Baseline in WOMAC Physical Function Subscale to Week 12 | -2.14 Unit on a scale | Standard Deviation 2.338 |
Secondary
Change From Baseline in WOMAC Stiffness Scores Over Time
The WOMAC stiffness function subscale consists of 2 questions assessing stiffness due to OA in the target knee. Stiffness is defined as a sensation of decreased ease of movement in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC stiffness function subscale score is calculated as the mean score from the 2 questions, where higher scores represent higher stiffness. Change from baseline in WOMAC stiffness score to Weeks 2, 4, 6, 8, 10, 12, and 18 is reported.
Time frame: Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), and 18 (Day 126)
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 2 | -1.30 Unit on a scale | Standard Deviation 1.887 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 18 | -2.04 Unit on a scale | Standard Deviation 2.192 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 12 | -2.29 Unit on a scale | Standard Deviation 2.034 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 6 | -2.13 Unit on a scale | Standard Deviation 1.837 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 4 | -1.88 Unit on a scale | Standard Deviation 1.938 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 8 | -1.99 Unit on a scale | Standard Deviation 2.125 |
| MEDl7352 Dose Level 1 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 10 | -2.13 Unit on a scale | Standard Deviation 2.06 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 10 | -2.99 Unit on a scale | Standard Deviation 2.277 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 8 | -2.85 Unit on a scale | Standard Deviation 2.26 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 4 | -2.26 Unit on a scale | Standard Deviation 2.146 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 2 | -2.06 Unit on a scale | Standard Deviation 2.015 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 12 | -3.06 Unit on a scale | Standard Deviation 2.38 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 6 | -2.79 Unit on a scale | Standard Deviation 2.307 |
| MEDl7352 Dose Level 2 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 18 | -2.76 Unit on a scale | Standard Deviation 2.401 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 8 | -2.85 Unit on a scale | Standard Deviation 2.103 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 2 | -1.85 Unit on a scale | Standard Deviation 1.927 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 4 | -2.33 Unit on a scale | Standard Deviation 2.127 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 6 | -2.72 Unit on a scale | Standard Deviation 1.871 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 10 | -2.96 Unit on a scale | Standard Deviation 1.977 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 12 | -3.06 Unit on a scale | Standard Deviation 2.04 |
| MEDl7352 Dose Level 3 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 18 | -2.86 Unit on a scale | Standard Deviation 1.988 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 6 | -2.97 Unit on a scale | Standard Deviation 2.428 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 10 | -3.29 Unit on a scale | Standard Deviation 2.091 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 4 | -2.55 Unit on a scale | Standard Deviation 2.368 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 18 | -3.17 Unit on a scale | Standard Deviation 1.797 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 12 | -3.43 Unit on a scale | Standard Deviation 2.407 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 2 | -2.13 Unit on a scale | Standard Deviation 2.02 |
| MEDl7352 Dose Level 4 | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 8 | -3.07 Unit on a scale | Standard Deviation 2.104 |
| Placebo | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 6 | -2.27 Unit on a scale | Standard Deviation 2.314 |
| Placebo | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 18 | -2.62 Unit on a scale | Standard Deviation 2.152 |
| Placebo | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 12 | -2.85 Unit on a scale | Standard Deviation 2.372 |
| Placebo | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 10 | -2.67 Unit on a scale | Standard Deviation 2.329 |
| Placebo | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 4 | -1.91 Unit on a scale | Standard Deviation 2.009 |
| Placebo | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 2 | -0.99 Unit on a scale | Standard Deviation 1.805 |
| Placebo | Change From Baseline in WOMAC Stiffness Scores Over Time | Week 8 | -2.39 Unit on a scale | Standard Deviation 2.633 |
Secondary
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.
Time frame: Day 1 through 41 weeks (maximum observed duration)
Population: Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Type 2 diabetes mellitus | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Activated partial thromboplastin time prolonged | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | COVID-19 | 16 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glycosuria | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypertriglyceridaemia | 1 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glycosylated haemoglobin increased | 1 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Neutropenia | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Leukopenia | 1 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Leukocyturia | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood uric acid increased | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose increased | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood folate decreased | 1 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | C-reactive protein increased | 1 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Proteinuria | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypercholesterolaemia | 1 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Vitamin D deficiency | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood creatine phosphokinase increased | 2 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Lymphopenia | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Anaemia | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperkalaemia | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypokalaemia | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyponatraemia | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Gamma-glutamyltransferase increased | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Coagulation factor increased | 1 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Activated partial thromboplastin time prolonged | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Proteinuria | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood creatine phosphokinase increased | 1 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Lymphopenia | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Coagulation factor increased | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypokalaemia | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Gamma-glutamyltransferase increased | 1 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glycosuria | 1 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | C-reactive protein increased | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Leukocyturia | 2 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Neutropenia | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Leukopenia | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glycosylated haemoglobin increased | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | COVID-19 | 5 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood uric acid increased | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Anaemia | 1 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperkalaemia | 2 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypercholesterolaemia | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose increased | 1 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypertriglyceridaemia | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyponatraemia | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Type 2 diabetes mellitus | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood folate decreased | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Vitamin D deficiency | 1 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood folate decreased | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood creatine phosphokinase increased | 1 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Anaemia | 1 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypertriglyceridaemia | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Activated partial thromboplastin time prolonged | 1 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Lymphopenia | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Proteinuria | 2 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperkalaemia | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyponatraemia | 1 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Coagulation factor increased | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Vitamin D deficiency | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Leukocyturia | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose increased | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Neutropenia | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Type 2 diabetes mellitus | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glycosuria | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypokalaemia | 1 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glycosylated haemoglobin increased | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Gamma-glutamyltransferase increased | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood uric acid increased | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | C-reactive protein increased | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypercholesterolaemia | 1 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | COVID-19 | 10 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Leukopenia | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood uric acid increased | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Leukopenia | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Lymphopenia | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Neutropenia | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypercholesterolaemia | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypertriglyceridaemia | 2 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyponatraemia | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Vitamin D deficiency | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glycosuria | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood folate decreased | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose increased | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glycosylated haemoglobin increased | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | COVID-19 | 12 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Anaemia | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperkalaemia | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypokalaemia | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Type 2 diabetes mellitus | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Leukocyturia | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Proteinuria | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Activated partial thromboplastin time prolonged | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Alanine aminotransferase increased | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Aspartate aminotransferase increased | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood creatine phosphokinase increased | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | C-reactive protein increased | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Coagulation factor increased | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Gamma-glutamyltransferase increased | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Lymphopenia | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood creatine phosphokinase increased | 2 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Leukocyturia | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Type 2 diabetes mellitus | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypokalaemia | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyperkalaemia | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Anaemia | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | COVID-19 | 8 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glycosylated haemoglobin increased | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood glucose increased | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood uric acid increased | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Blood folate decreased | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Glycosuria | 2 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Vitamin D deficiency | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Leukopenia | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | C-reactive protein increased | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hyponatraemia | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypertriglyceridaemia | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Hypercholesterolaemia | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Gamma-glutamyltransferase increased | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Coagulation factor increased | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Neutropenia | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Aspartate aminotransferase increased | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Alanine aminotransferase increased | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Activated partial thromboplastin time prolonged | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Proteinuria | 2 Participants |
Secondary
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormalfinding in the vital sign parameters (body temperature, supine and standing blood pressure, pulse rate, and respiratory rate).
Time frame: Day 1 through 41 weeks (maximum observed duration)
Population: Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertensive crisis | 1 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Tachycardia | 1 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Tachycardia paroxysmal | 1 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypotension | 1 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Bradycardia | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypotension | 1 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Bradycardia | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Tachycardia | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Tachycardia paroxysmal | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 2 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertensive crisis | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Tachycardia paroxysmal | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 3 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypotension | 1 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertensive crisis | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Bradycardia | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Tachycardia | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Bradycardia | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertensive crisis | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Tachycardia paroxysmal | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypotension | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Tachycardia | 0 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 1 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Bradycardia | 1 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Tachycardia | 0 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Tachycardia paroxysmal | 0 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 0 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertensive crisis | 0 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Orthostatic hypotension | 1 Participants |
Secondary
Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints
Number of participants with abnormal X-ray and/or MRI of large joints is reported.
Time frame: Baseline (Day -45 to -1) and Week 32
Population: Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints | MRI | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints | X-ray | 1 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints | MRI | 1 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints | X-ray | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints | MRI | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints | X-ray | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints | X-ray | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints | MRI | 0 Participants |
| Placebo | Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints | MRI | 0 Participants |
| Placebo | Number of Participants With Abnormal X-ray and/or Magnetic Resonance Imaging (MRI) of Large Joints | X-ray | 2 Participants |
Secondary
Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs)
Number of participants with clinically significant abnormal ECGs are reported.
Time frame: Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 8 (Day 56), 10 (Day 70), 12 (Day 84), 28 (Day 168), and 32 (Day 224)
Population: Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Number of participants analyzed (N) denotes the number of participants who were evaluable for the specified outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 2 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 10 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 32 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 8 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 0 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 28 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 4 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 12 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 0 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 12 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 32 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 2 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 4 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 8 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 10 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 28 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 10 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 8 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 0 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 28 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 2 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 32 | 1 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 12 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 4 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 4 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 0 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 2 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 8 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 10 | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 12 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 28 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 32 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 8 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 32 | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 28 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 2 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 0 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 4 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 12 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) | Week 10 | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination
Number of participants with clinically significant abnormal findings in neurological examination is reported. The neurological examination included assessment of mental status, cranial nerves, motor examination (muscle strength and tone), upper and lower extremity deep tendon reflexes, plantar responses, sensory system examination, coordination, and gait.
Time frame: Baseline (Day -45 to Day -1), Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), 18 (Day 126), 28 (Day 168), 32 (Day 224), and 36 (Day 252)
Population: Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 36 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 12 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 8 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 10 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 0 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 32 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 2 | 1 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 28 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 4 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Baseline | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 18 | 0 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 6 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 4 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 2 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 10 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 36 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 8 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 32 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 12 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 18 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 0 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Baseline | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 6 | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 28 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 2 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Baseline | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 0 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 28 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 4 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 6 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 8 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 10 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 12 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 18 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 32 | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 36 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 4 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 28 | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 0 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 12 | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 36 | 2 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 32 | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 18 | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 6 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 8 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 2 | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Baseline | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 10 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 0 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 4 | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 12 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 2 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 36 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 18 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 10 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 28 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Baseline | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 32 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 8 | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormal Findings in Neurological Examination | Week 6 | 0 Participants |
Secondary
Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs
Number of participants with clinically significant findings in physical examination reported as TEAE are reported. A physical examination included assessments of general appearance, skin, head and neck, examination of the oral cavity for any lesions, lymph nodes, thyroid, abdomen (bowel sounds, liver, and spleen palpation), back (including costovertebral angle tenderness), musculoskeletal/extremities, cardiovascular, and respiratory systems.
Time frame: Day 1 through 41 weeks (maximum observed duration)
Population: Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MEDl7352 Dose Level 1 | Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs | 0 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs | 0 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs | 0 Participants |
Secondary
Number of Participants With Injection Site Reactions
Number of participants with injection site reactions are reported.
Time frame: Day 1 through 41 weeks (maximum observed duration)
Population: Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MEDl7352 Dose Level 1 | Number of Participants With Injection Site Reactions | 2 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Injection Site Reactions | 3 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Injection Site Reactions | 0 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Injection Site Reactions | 4 Participants |
| Placebo | Number of Participants With Injection Site Reactions | 0 Participants |
Secondary
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352
Number of participants with ADA to MEDI7352 are reported. Treatment-induced ADA positive is defined as ADA negative at baseline and positive at least 1 post-baseline ADA assessment. Treatment-boosted ADA positive is defined as ADA positive at baseline, and the baseline titre is boosted by greater than the variability of the assay (commonly 4-fold) at \>= 1 post-baseline timepoint. Persistent positive is defined as ADA negative at baseline and having at least 2 post-baseline ADA positive assessments (with \>= 16 weeks between first and last positive) or ADA positive at last post-baseline assessment. Transiently positive is defined as ADA negative at baseline and at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.
Time frame: Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224
Population: ADA evaluable participants included all participants in the safety analysis set who have a non-missing baseline and at least one non-missing post-baseline ADA results. Number of participants analyzed (N) denotes the number of participants who were evaluable for the specified outcome measure. Number analyzed (n) denotes those participants who had adequate ADA sample.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-boosted ADA positive | 6 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-induced ADA positive | 52 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Persistent positive ADA | 43 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Transiently positive ADA | 9 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-boosted ADA positive | 9 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-induced ADA positive | 49 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Transiently positive ADA | 10 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Persistent positive ADA | 39 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-induced ADA positive | 42 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-boosted ADA positive | 8 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Transiently positive ADA | 9 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Persistent positive ADA | 33 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-induced ADA positive | 52 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Persistent positive ADA | 42 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-boosted ADA positive | 2 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Transiently positive ADA | 10 Participants |
| Placebo | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Transiently positive ADA | 2 Participants |
| Placebo | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Persistent positive ADA | 4 Participants |
| Placebo | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-induced ADA positive | 6 Participants |
| Placebo | Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 | Treatment-boosted ADA positive | 2 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time frame: Day 1 through 41 weeks (maximum observed duration)
Population: Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 51 Participants |
| MEDl7352 Dose Level 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 3 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 45 Participants |
| MEDl7352 Dose Level 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 5 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 54 Participants |
| MEDl7352 Dose Level 3 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 3 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 1 Participants |
| MEDl7352 Dose Level 4 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 51 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 41 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 2 Participants |
Secondary
Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time
The NRS is an 11-point Likert scale used to assess pain, where participants were asked to describe their average pain in the target knee by identifying a number from 0 = no pain to 10 = most severe pain imaginable over the previous 24 hours. This will be recorded on a daily basis at approximately the same time every morning via ePRO diary. Percentage of participants with \>= 30% and \>= 50% reductions in weekly average of daily NRS pain score are reported.
Time frame: Baseline (Day -7 to Day -1, inclusive), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 8 | 56.4 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 18 | 26.2 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 12 | 58.0 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 12 | 44.0 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 8 | 32.7 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 4 | 47.5 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 2 | 34.8 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 4 | 24.6 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 2 | 15.2 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 18 | 42.9 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 4 | 50.0 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 2 | 34.4 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 8 | 67.8 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 12 | 76.4 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 18 | 72.9 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 2 | 25.0 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 4 | 32.8 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 8 | 45.8 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 12 | 54.5 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 18 | 54.2 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 2 | 29.2 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 12 | 49.1 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 8 | 67.2 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 12 | 65.5 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 4 | 64.1 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 18 | 67.3 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 4 | 40.6 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 2 | 41.5 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 18 | 50.0 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 8 | 54.1 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 4 | 53.8 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 18 | 52.6 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 2 | 43.9 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 8 | 61.5 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 2 | 30.3 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 8 | 57.7 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 12 | 54.5 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 4 | 36.9 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 12 | 72.7 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 18 | 65.8 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 12 | 47.8 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 12 | 26.1 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 18 | 54.5 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 2 | 13.8 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 18 | 29.5 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 4 | 15.6 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 2 | 21.5 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=50%: Week 8 | 26.9 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 8 | 42.3 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Daily NRS Pain Score Over Time | >=30%: Week 4 | 29.7 Percentage of participants |
Secondary
Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time
The WOMAC multiscale index is used to assess pain, stiffness, and joint functionality in the past 48 hours in participants with OA of the knee or hip. The WOMAC pain subscale consists of 5 questions assessing the participant's pain due to OA in the target knee. Each question was scored on an NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 5 questions, where higher scores represent higher pain. Percentage of participants with \>= 30% and \>= 50% reductions in WOMAC pain subscale score over time are reported.
Time frame: Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 8 | 55.6 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 18 | 33.3 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 12 | 59.6 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 12 | 31.9 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 8 | 35.2 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 4 | 40.4 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 2 | 30.2 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 4 | 24.6 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 2 | 14.3 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 18 | 51.1 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 4 | 54.1 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 2 | 39.7 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 8 | 64.3 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 12 | 68.5 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 18 | 70.6 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 2 | 23.8 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 4 | 31.1 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 8 | 46.4 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 12 | 51.9 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 18 | 51.0 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 2 | 17.5 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 12 | 50.0 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 8 | 64.9 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 12 | 67.3 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 4 | 61.7 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 18 | 62.7 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 4 | 40.0 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 2 | 36.5 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 18 | 43.1 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 8 | 49.1 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 4 | 61.0 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 18 | 59.0 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 2 | 50.8 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 8 | 71.4 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 2 | 33.8 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 8 | 57.1 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 12 | 62.5 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 4 | 55.9 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 12 | 75.0 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 18 | 76.9 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 12 | 66.7 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 12 | 42.9 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 18 | 69.8 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 2 | 10.3 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 18 | 41.9 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 4 | 26.2 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 2 | 24.1 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=50%: Week 8 | 34.8 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 8 | 56.5 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Pain Subscale Score Over Time | >=30%: Week 4 | 47.5 Percentage of participants |
Secondary
Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time
The WOMAC PF subscale consists of 17 questions assessing the participant's difficulty in performing activities of daily living due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC PF subscale score is calculated as the mean score from all 17 questions, where higher scores represent worse function. Percentage of participants with \>= 30% and \>= 50% reductions in WOMAC physical function subscale over time are reported.
Time frame: Baseline (Week 0; Day 1), Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 4 | 28.1 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 18 | 42.2 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 2 | 14.3 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 18 | 33.3 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 4 | 47.4 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 2 | 30.2 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 12 | 34.0 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 8 | 50.0 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 8 | 33.3 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 12 | 42.6 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 2 | 22.2 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 8 | 51.8 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 18 | 72.5 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 18 | 45.1 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 12 | 72.2 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 8 | 64.3 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 12 | 46.3 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 2 | 42.9 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 4 | 52.5 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 4 | 31.1 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 8 | 63.2 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 2 | 39.7 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 4 | 61.7 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 12 | 67.3 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 18 | 64.7 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 2 | 23.8 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 4 | 41.7 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 8 | 47.4 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 12 | 50.0 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 18 | 39.2 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 4 | 54.2 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 4 | 59.3 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 12 | 72.5 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 8 | 69.4 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 12 | 62.5 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 2 | 47.7 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 18 | 74.4 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 18 | 59.0 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 8 | 57.1 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 2 | 33.8 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 8 | 26.1 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 8 | 47.8 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 4 | 19.7 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 4 | 37.7 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 2 | 12.1 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 2 | 22.4 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 18 | 34.9 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 18 | 60.5 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=30%: Week 12 | 54.8 Percentage of participants |
| Placebo | Percentage of Participants With >= 30% and >= 50% Reductions in WOMAC Physical Function Subscale Over Time | >=50%: Week 12 | 35.7 Percentage of participants |
Secondary
Percentage of Participants With Improvement of >= 2 Points in PGA of OA
The PGA of OA was a 5-point Likert scale used to assess symptoms and activity impairment due to OA of the knee. Participants were asked to identify a number from 1 = very good (asymptomatic and no limitation to normal activities) to 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities) based on the question Considering all the ways that OA of the knee affects you, how are you feeling today?. Percentage of participants with improvement of \>= 2 points in PGA of OA at Weeks 2, 4, 8, 12, and 18 is reported.
Time frame: Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 12 | 10.9 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 2 | 9.7 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 18 | 2.3 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 4 | 8.9 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 8 | 17.0 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 12 | 18.9 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 8 | 23.6 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 4 | 26.7 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 18 | 20.0 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 2 | 9.7 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 8 | 25.9 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 2 | 16.7 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 4 | 24.6 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 12 | 20.4 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 18 | 22.9 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 18 | 25.6 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 2 | 12.3 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 12 | 32.5 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 8 | 28.6 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 4 | 22.0 Percentage of participants |
| Placebo | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 8 | 4.4 Percentage of participants |
| Placebo | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 12 | 7.3 Percentage of participants |
| Placebo | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 2 | 7.0 Percentage of participants |
| Placebo | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 18 | 4.7 Percentage of participants |
| Placebo | Percentage of Participants With Improvement of >= 2 Points in PGA of OA | Week 4 | 6.7 Percentage of participants |
Secondary
Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition
The OMERACT-OARSI responder index is calculated from the WOMAC Pain subscale, the WOMAC Physical Function Subscale and the PGA of OA. A participant is classified as a responder if: 1. \>= 2-point absolute change from Baseline to Week X or a \>= 50% improvement is reported in the WOMAC Pain or the PF subscales; 2. At least 2 of the following 3 conditions are true: \>= 1-point absolute change from Baseline to Week X or \>= 20% improvement is reported in the WOMAC Pain subscale, \>= 1-point absolute change from Baseline to Week X or \>= 20% improvement is reported in the WOMAC PF subscale or \>= 1-point absolute change from Baseline to Week X is reported in the PGA of OA. Percentage of responder participants are reported.
Time frame: Weeks 2 (Day 14), 4 (Day 28), 8 (Day 56), 12 (Day 84), and 18 (Day 126)
Population: FAS included all randomized participants analyzed according to the intent-to-treat principle whereby randomized study treatment will be analyzed regardless of the study treatment actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDl7352 Dose Level 1 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 12 | 59.2 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 2 | 47.7 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 18 | 55.3 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 4 | 59.3 Percentage of participants |
| MEDl7352 Dose Level 1 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 8 | 58.9 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 12 | 80.0 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 8 | 80.7 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 4 | 67.7 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 18 | 78.8 Percentage of participants |
| MEDl7352 Dose Level 2 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 2 | 62.5 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 8 | 80.0 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 2 | 61.8 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 4 | 73.4 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 12 | 80.0 Percentage of participants |
| MEDl7352 Dose Level 3 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 18 | 72.2 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 18 | 80.5 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 2 | 59.7 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 12 | 85.7 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 8 | 86.3 Percentage of participants |
| MEDl7352 Dose Level 4 | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 4 | 65.6 Percentage of participants |
| Placebo | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 8 | 68.6 Percentage of participants |
| Placebo | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 12 | 67.4 Percentage of participants |
| Placebo | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 2 | 40.6 Percentage of participants |
| Placebo | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 18 | 70.2 Percentage of participants |
| Placebo | Percentage of Responder Participants Measured by Osteoarthritis Research Society International (OARSI) Responder Index Using Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Definition | Week 4 | 63.1 Percentage of participants |
Secondary
Serum Concentration of MEDI7352
Serum concentration of MEDI7352 is reported.
Time frame: Baseline (Day 1), Day 7; pre-dose on Days 14, 28, 42, 56, and 70; and on Days 74, 77, 84, 126, and 224
Population: Pharmacokinetic (PK) analysis set included participants who received at least one dose of double-blind study treatment per the protocol for whom any post-baseline PK data are available and who did not violate or deviate from the protocol in ways that would significantly affect the PK analyses. Number of participants analyzed (N) denotes those participants who were analyzed for this outcome measure. Number analyzed (n) denotes those participants who had adequate serum samples.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MEDl7352 Dose Level 1 | Serum Concentration of MEDI7352 | Day 28 | 11.025 ng/mL | Geometric Coefficient of Variation 853.538 |
| MEDl7352 Dose Level 1 | Serum Concentration of MEDI7352 | Day 7 | 326.863 ng/mL | Geometric Coefficient of Variation 98.989 |
| MEDl7352 Dose Level 1 | Serum Concentration of MEDI7352 | Day 42 | 5.895 ng/mL | Geometric Coefficient of Variation 846.517 |
| MEDl7352 Dose Level 1 | Serum Concentration of MEDI7352 | Day 14 | 50.337 ng/mL | Geometric Coefficient of Variation 538.604 |
| MEDl7352 Dose Level 1 | Serum Concentration of MEDI7352 | Day 77 | 5.011 ng/mL | Geometric Coefficient of Variation 1322.708 |
| MEDl7352 Dose Level 1 | Serum Concentration of MEDI7352 | Day 74 | 10.943 ng/mL | Geometric Coefficient of Variation 1833.135 |
| MEDl7352 Dose Level 2 | Serum Concentration of MEDI7352 | Day 28 | 28.332 ng/mL | Geometric Coefficient of Variation 2745.856 |
| MEDl7352 Dose Level 2 | Serum Concentration of MEDI7352 | Day 56 | 6.625 ng/mL | Geometric Coefficient of Variation 2133.678 |
| MEDl7352 Dose Level 2 | Serum Concentration of MEDI7352 | Day 7 | 681.322 ng/mL | Geometric Coefficient of Variation 159.914 |
| MEDl7352 Dose Level 2 | Serum Concentration of MEDI7352 | Day 77 | 9.356 ng/mL | Geometric Coefficient of Variation 3099.752 |
| MEDl7352 Dose Level 2 | Serum Concentration of MEDI7352 | Day 14 | 144.242 ng/mL | Geometric Coefficient of Variation 475.607 |
| MEDl7352 Dose Level 2 | Serum Concentration of MEDI7352 | Day 42 | 12.375 ng/mL | Geometric Coefficient of Variation 2578.767 |
| MEDl7352 Dose Level 2 | Serum Concentration of MEDI7352 | Day 74 | 22.074 ng/mL | Geometric Coefficient of Variation 4305.129 |
| MEDl7352 Dose Level 3 | Serum Concentration of MEDI7352 | Day 56 | 20.546 ng/mL | Geometric Coefficient of Variation 13626.951 |
| MEDl7352 Dose Level 3 | Serum Concentration of MEDI7352 | Day 70 | 17.124 ng/mL | Geometric Coefficient of Variation 15147.088 |
| MEDl7352 Dose Level 3 | Serum Concentration of MEDI7352 | Day 7 | 2149.062 ng/mL | Geometric Coefficient of Variation 109.2763 |
| MEDl7352 Dose Level 3 | Serum Concentration of MEDI7352 | Day 74 | 116.544 ng/mL | Geometric Coefficient of Variation 25316.322 |
| MEDl7352 Dose Level 3 | Serum Concentration of MEDI7352 | Day 14 | 379.882 ng/mL | Geometric Coefficient of Variation 488.933 |
| MEDl7352 Dose Level 3 | Serum Concentration of MEDI7352 | Day 84 | 10.482 ng/mL | Geometric Coefficient of Variation 6086.596 |
| MEDl7352 Dose Level 3 | Serum Concentration of MEDI7352 | Day 28 | 43.644 ng/mL | Geometric Coefficient of Variation 6705.491 |
| MEDl7352 Dose Level 3 | Serum Concentration of MEDI7352 | Day 77 | 47.108 ng/mL | Geometric Coefficient of Variation 39692.068 |
| MEDl7352 Dose Level 3 | Serum Concentration of MEDI7352 | Day 42 | 30.005 ng/mL | Geometric Coefficient of Variation 11978.84 |
| MEDl7352 Dose Level 4 | Serum Concentration of MEDI7352 | Day 84 | 43.062 ng/mL | Geometric Coefficient of Variation 13640.856 |
| MEDl7352 Dose Level 4 | Serum Concentration of MEDI7352 | Day 7 | 3582.265 ng/mL | Geometric Coefficient of Variation 364.2 |
| MEDl7352 Dose Level 4 | Serum Concentration of MEDI7352 | Day 14 | 650.864 ng/mL | Geometric Coefficient of Variation 624.642 |
| MEDl7352 Dose Level 4 | Serum Concentration of MEDI7352 | Day 28 | 222.665 ng/mL | Geometric Coefficient of Variation 3963.855 |
| MEDl7352 Dose Level 4 | Serum Concentration of MEDI7352 | Day 42 | 116.951 ng/mL | Geometric Coefficient of Variation 14993.947 |
| MEDl7352 Dose Level 4 | Serum Concentration of MEDI7352 | Day 56 | 85.779 ng/mL | Geometric Coefficient of Variation 15987.305 |
| MEDl7352 Dose Level 4 | Serum Concentration of MEDI7352 | Day 70 | 57.042 ng/mL | Geometric Coefficient of Variation 18183.372 |
| MEDl7352 Dose Level 4 | Serum Concentration of MEDI7352 | Day 74 | 551.099 ng/mL | Geometric Coefficient of Variation 18558.506 |
| MEDl7352 Dose Level 4 | Serum Concentration of MEDI7352 | Day 77 | 271.511 ng/mL | Geometric Coefficient of Variation 36387.885 |
| Unknown | Serum Concentration of MEDI7352 | Day 1 | — ng/mL | — |
| Unknown | Serum Concentration of MEDI7352 | Day 126 | — ng/mL | — |
| Unknown | Serum Concentration of MEDI7352 | Day 224 | — ng/mL | — |
Secondary
Total Neuropathy Score-Nurse (TNSn) Over Time
The TNSn, is a semiquantitative clinical assessment of peripheral nervous system function. The TNSn assessment is collected as scores of motor symptom, autonomic symptom, pin sensibility, sensory symptom, and vibration sensibility score. Each neuropathy item is scored on a 0 to 4 scale with total score ranging from 0 to 20. Higher total scores correlate with more severe neuropathy.
Time frame: Baseline (Day -45 to Day -1), Weeks 0 (Day 1), 2 (Day 14), 4 (Day 28), 6 (Day 42), 8 (Day 56), 10 (Day 70), 12 (Day 84), 28 (Day 196), and 32 (Day 224)
Population: Safety analysis set included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MEDl7352 Dose Level 1 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 32 | 1.5 Unit on a scale | Standard Deviation 1.98 |
| MEDl7352 Dose Level 1 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 8 | 1.0 Unit on a scale | Standard Deviation 1.65 |
| MEDl7352 Dose Level 1 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 4 | 1.0 Unit on a scale | Standard Deviation 1.66 |
| MEDl7352 Dose Level 1 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 6 | 1.0 Unit on a scale | Standard Deviation 1.55 |
| MEDl7352 Dose Level 1 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 28 | 1.7 Unit on a scale | Standard Deviation 2.25 |
| MEDl7352 Dose Level 1 | Total Neuropathy Score-Nurse (TNSn) Over Time | Baseline | 1.5 Unit on a scale | Standard Deviation 2.4 |
| MEDl7352 Dose Level 1 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 12 | 0.9 Unit on a scale | Standard Deviation 1.35 |
| MEDl7352 Dose Level 1 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 10 | 1.1 Unit on a scale | Standard Deviation 1.85 |
| MEDl7352 Dose Level 1 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 0 | 1.3 Unit on a scale | Standard Deviation 1.92 |
| MEDl7352 Dose Level 1 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 2 | 1.1 Unit on a scale | Standard Deviation 1.84 |
| MEDl7352 Dose Level 2 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 2 | 1.6 Unit on a scale | Standard Deviation 2.42 |
| MEDl7352 Dose Level 2 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 8 | 1.1 Unit on a scale | Standard Deviation 1.86 |
| MEDl7352 Dose Level 2 | Total Neuropathy Score-Nurse (TNSn) Over Time | Baseline | 1.4 Unit on a scale | Standard Deviation 1.94 |
| MEDl7352 Dose Level 2 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 0 | 1.7 Unit on a scale | Standard Deviation 2.26 |
| MEDl7352 Dose Level 2 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 6 | 1.4 Unit on a scale | Standard Deviation 2.23 |
| MEDl7352 Dose Level 2 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 10 | 1.3 Unit on a scale | Standard Deviation 2.06 |
| MEDl7352 Dose Level 2 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 12 | 1.2 Unit on a scale | Standard Deviation 1.88 |
| MEDl7352 Dose Level 2 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 32 | 1.0 Unit on a scale | Standard Deviation 1.5 |
| MEDl7352 Dose Level 2 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 28 | 3.3 Unit on a scale | Standard Deviation 2.69 |
| MEDl7352 Dose Level 2 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 4 | 1.3 Unit on a scale | Standard Deviation 1.98 |
| MEDl7352 Dose Level 3 | Total Neuropathy Score-Nurse (TNSn) Over Time | Baseline | 1.0 Unit on a scale | Standard Deviation 1.56 |
| MEDl7352 Dose Level 3 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 4 | 0.9 Unit on a scale | Standard Deviation 1.54 |
| MEDl7352 Dose Level 3 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 8 | 0.6 Unit on a scale | Standard Deviation 0.91 |
| MEDl7352 Dose Level 3 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 12 | 0.8 Unit on a scale | Standard Deviation 1.37 |
| MEDl7352 Dose Level 3 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 0 | 1.4 Unit on a scale | Standard Deviation 2.03 |
| MEDl7352 Dose Level 3 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 2 | 1.2 Unit on a scale | Standard Deviation 1.97 |
| MEDl7352 Dose Level 3 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 6 | 0.9 Unit on a scale | Standard Deviation 1.73 |
| MEDl7352 Dose Level 3 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 10 | 0.8 Unit on a scale | Standard Deviation 1.53 |
| MEDl7352 Dose Level 3 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 28 | 2.5 Unit on a scale | Standard Deviation 2.83 |
| MEDl7352 Dose Level 3 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 32 | 0.5 Unit on a scale | Standard Deviation 0.88 |
| MEDl7352 Dose Level 4 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 6 | 0.9 Unit on a scale | Standard Deviation 1.48 |
| MEDl7352 Dose Level 4 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 2 | 1.0 Unit on a scale | Standard Deviation 1.7 |
| MEDl7352 Dose Level 4 | Total Neuropathy Score-Nurse (TNSn) Over Time | Baseline | 1.2 Unit on a scale | Standard Deviation 1.69 |
| MEDl7352 Dose Level 4 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 10 | 0.7 Unit on a scale | Standard Deviation 1.2 |
| MEDl7352 Dose Level 4 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 0 | 1.5 Unit on a scale | Standard Deviation 2.29 |
| MEDl7352 Dose Level 4 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 12 | 0.7 Unit on a scale | Standard Deviation 1.23 |
| MEDl7352 Dose Level 4 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 28 | 0.8 Unit on a scale | Standard Deviation 0.92 |
| MEDl7352 Dose Level 4 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 32 | 0.9 Unit on a scale | Standard Deviation 1.64 |
| MEDl7352 Dose Level 4 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 8 | 0.8 Unit on a scale | Standard Deviation 1.62 |
| MEDl7352 Dose Level 4 | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 4 | 0.9 Unit on a scale | Standard Deviation 1.61 |
| Placebo | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 0 | 1.8 Unit on a scale | Standard Deviation 2.26 |
| Placebo | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 2 | 1.5 Unit on a scale | Standard Deviation 2.18 |
| Placebo | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 12 | 1.1 Unit on a scale | Standard Deviation 2 |
| Placebo | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 8 | 1.2 Unit on a scale | Standard Deviation 1.84 |
| Placebo | Total Neuropathy Score-Nurse (TNSn) Over Time | Baseline | 1.5 Unit on a scale | Standard Deviation 2.02 |
| Placebo | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 28 | 2.9 Unit on a scale | Standard Deviation 2.67 |
| Placebo | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 32 | 1.0 Unit on a scale | Standard Deviation 1.98 |
| Placebo | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 4 | 1.4 Unit on a scale | Standard Deviation 2.16 |
| Placebo | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 10 | 1.1 Unit on a scale | Standard Deviation 2.1 |
| Placebo | Total Neuropathy Score-Nurse (TNSn) Over Time | Week 6 | 1.5 Unit on a scale | Standard Deviation 2.51 |