Osteoarthritis of the Knee or Hip
Conditions
Brief summary
The primary objective of the study is to describe the safety and tolerability of fasinumab, including adverse events of special interest (AESIs), in patients with pain due to radiographically-confirmed OA of the knee or hip.
Interventions
DRUGFasinumab
Participants will receive sub-cutaneous (SC) injections of fasinumab
DRUGPlacebo
Participants will receive sub-cutaneous (SC) injections of matching placebo
Sponsors
Teva Pharmaceutical Industries, Ltd.
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male or female ≥18 years of age at the screening visit 2. Clinical diagnosis of OA of the knee or hip based on the American College of Rheumatology criteria with radiologic evidence of OA (K-L score ≥2) for the index joint at the screening visit 3. Moderate to severe pain in the index joint defined as a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) average pain subscale score of ≥4 4. A history of 12 weeks of analgesic use for OA of the knee or hip 5. History of regular use of analgesic medications for OA pain Key
Exclusion criteria
1. History or presence at the screening visit of non OA inflammatory joint disease 2. History or presence on imaging of arthropathy, stress fracture, recent stress fracture, neuropathic joint arthropathy, hip dislocation, knee dislocation, congenital hip dysplasia with degenerative joint disease, extensive subchondral cysts, evidence of bone fragmentation or collapse, or primary metastatic tumor with the exception of chondromas or pathologic fracture during the screening period 3. Signs or symptoms of carpal tunnel syndrome within 6 months of screening 4. Patient is not a candidate for MRI 5. Is scheduled for a joint replacement surgery to be performed during the study period 6. Systemic (i.e., oral or intramuscular) corticosteroids within 30 days prior to the screening visit. 7. History or presence at the screening visit of multiple sclerosis, autonomic neuropathy, diabetic neuropathy, or other peripheral neuropathy, including reflex sympathetic dystrophy 8. History or diagnosis of chronic autonomic failure syndrome including pure autonomic failure, multiple system atrophy 9. Pregnant or breast-feeding women 10. Women of childbearing potential who have a positive pregnancy test result or do not have their pregnancy test result at baseline Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 16 in WOMAC Physical Function Subscale Score | Baseline to Week 16 | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. |
| Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Baseline up to week 72 | Immunogenicity was characterized by ADA responses & titers. Responses categories: Negative - ADA negative response at all time points, regardless of missing samples; Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses less than (\<) 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, greater than or equal to (≥) 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response in the fasinumab ADA assay post first dose when baseline results = negative or missing. |
| Change From Baseline to Week 16 in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score | Baseline to Week 16 | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. |
| Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) | Baseline up to week 52 | — |
| Number of Participants With Any Serious TEAE | Baseline up to week 52 | — |
| Number of Participants With Any Adverse Event (AE) up to Week 72 | Baseline up to week 72 | — |
| Number of Participants With Any Serious AE up to Week 72 | Baseline up to week 72 | — |
| Number of Participants With Adjudicated Arthropathy (AA) | Baseline up to week 52 and week 72 | Adjudicated arthropathy (AA) is a composite term that encompasses the following conditions: Rapidly progressive OA type 1 and 2, Subchondral insufficiency fractures, and Primary Osteonecrosis. AAs were also evaluated to determine if they met Destructive Arthropathy criteria. |
| Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Baseline up to week 52 and week 72 | DA is a unique clinical form of rapidly destructive arthropathy over and above that seen in the normal progression of OA. DA criteria can be associated with Rapidly Progressive OA type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee. |
| Number of Participants With at Least One Peripheral Sensory Event That Required a Neurology Consultation | Baseline up to week 72 | Any participant with a peripheral sensory event that persisted for 2 months was referred for a neurology or other specialty consultation and reported as an adverse event of special interest (AESI). |
| Number of Participants With Sympathetic Nervous System (SNS) Dysfunction | Baseline up to week 72 | Potential events of sympathetic nervous system (SNS) dysfunction were monitored throughout the study through physical examination, AE reporting, assessment of orthostatic hypotension, and the Survey of Autonomic Symptoms. Sympathetic nervous system dysfunction was diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist. |
| Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Baseline up to weeks 52, 72, and end of study (52 weeks post last dose) | All joint replacement surgery events regardless of cause at weeks 52 and 72. An end of study phone contact was also conducted approximately 52 weeks following the last dose of study drug. |
| Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Baseline to week 52 | Number of participants with potentially clinically significant abnormal values in hematology, chemistry, and urinalysis during the treatment period were reported. Clinical significance was determined by the investigator. |
| Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | End of treatment up to week 72 | Number of participants with potentially clinically significant abnormal values in hematology, chemistry, and urinalysis during the post-treatment period were reported. Clinical significance was determined by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With ≥30% Reduction From Baseline to Week 16 in the WOMAC Pain Subscale Score | Baseline to Week 16 | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. Participants who achieved a response, where response was defined as an improvement by ≥30% in WOMAC pain subscale score |
| Change From Baseline to Week 16 in Patient Global Assessment (PGA) Score of Osteoarthritis | Baseline to Week 16 | The PGA of OA is a patient-rated assessment of current disease state on a 5-point Likert scale (1 = very good; 2 = good; 3 = fair; 4 = poor; and 5 = very poor). |
Countries
Bulgaria, Chile, Colombia, Denmark, Estonia, Germany, Hong Kong, Hungary, Italy, Lithuania, Mexico, Peru, Poland, Romania, Russia, South Africa, Spain, Sweden, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
13,945 participants were screened. Of those, 5,331 met the eligibility criteria and were randomized to 1 of 7 treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| Fasinumab-matching Placebo Q4W/Q8W Participants received fasinumab matching placebo SC injection, Q4W or Q8W from Day 1 up to 52 weeks. | 1,260 |
| Fasinumab 1 mg SC Q8W Participants received fasinumab 1 mg SC injection, Q8W from day 1 up to 52 weeks. | 971 |
| Fasinumab 1 mg SC Q4W Participants received fasinumab 1 mg SC injection Q4W from day 1 up to 52 weeks. | 975 |
| Fasinumab 3 mg SC Q4W Participants received fasinumab 3 mg SC injection, Q4W from day 1 up to 52 weeks. | 214 |
| Fasinumab 6 mg SC Q8W Participants received fasinumab 6 mg SC injection, Q8W from day 1 up to 52 weeks. | 1,680 |
| Fasinumab 6 mg SC Q4W Participants received fasinumab 6 mg SC injection Q4W from day 1 up to 37 weeks of 52-week treatment period. | 116 |
| Fasinumab 9 mg SC Q4W Participants received fasinumab 9 mg SC injection, Q4W from day 1 up to 37 weeks of 52-week treatment period. | 115 |
| Total | 5,331 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 64 | 39 | 42 | 16 | 189 | 9 | 9 |
| Overall Study | Death | 9 | 5 | 8 | 0 | 12 | 1 | 0 |
| Overall Study | Lack of Efficacy | 50 | 23 | 12 | 2 | 29 | 2 | 3 |
| Overall Study | Lost to Follow-up | 77 | 24 | 25 | 7 | 88 | 8 | 11 |
| Overall Study | Missing data | 0 | 1 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 38 | 19 | 14 | 73 | 143 | 14 | 15 |
| Overall Study | Protocol Violation | 35 | 23 | 26 | 4 | 35 | 4 | 5 |
| Overall Study | Withdrawal by Subject | 187 | 99 | 91 | 18 | 248 | 22 | 28 |
Baseline characteristics
| Characteristic | Fasinumab 9 mg SC Q4W | Total | Fasinumab-matching Placebo Q4W/Q8W | Fasinumab 1 mg SC Q8W | Fasinumab 1 mg SC Q4W | Fasinumab 3 mg SC Q4W | Fasinumab 6 mg SC Q8W | Fasinumab 6 mg SC Q4W |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.4 Years STANDARD_DEVIATION 9.89 | 64.0 Years STANDARD_DEVIATION 9.28 | 63.7 Years STANDARD_DEVIATION 9.24 | 65.0 Years STANDARD_DEVIATION 9.24 | 65.1 Years STANDARD_DEVIATION 8.57 | 65.3 Years STANDARD_DEVIATION 9.19 | 62.9 Years STANDARD_DEVIATION 9.61 | 62.4 Years STANDARD_DEVIATION 8.38 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 622 Participants | 117 Participants | 177 Participants | 182 Participants | 6 Participants | 124 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 107 Participants | 4686 Participants | 1139 Participants | 791 Participants | 787 Participants | 207 Participants | 1547 Participants | 108 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 23 Participants | 4 Participants | 3 Participants | 6 Participants | 1 Participants | 9 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 131 Participants | 19 Participants | 50 Participants | 53 Participants | 0 Participants | 8 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 93 Participants | 25 Participants | 7 Participants | 9 Participants | 0 Participants | 52 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 542 Participants | 156 Participants | 64 Participants | 66 Participants | 16 Participants | 213 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 327 Participants | 63 Participants | 91 Participants | 109 Participants | 8 Participants | 55 Participants | 1 Participants |
| Race (NIH/OMB) White | 102 Participants | 4236 Participants | 996 Participants | 759 Participants | 738 Participants | 190 Participants | 1352 Participants | 99 Participants |
| Sex: Female, Male Female | 76 Participants | 3886 Participants | 913 Participants | 723 Participants | 705 Participants | 149 Participants | 1237 Participants | 83 Participants |
| Sex: Female, Male Male | 39 Participants | 1445 Participants | 347 Participants | 248 Participants | 270 Participants | 65 Participants | 443 Participants | 33 Participants |
| Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain Subscale Score | — | 6.6 Score on a Scale STANDARD_DEVIATION 1.47 | 6.6 Score on a Scale STANDARD_DEVIATION 1.55 | 6.70 Score on a Scale STANDARD_DEVIATION 1.44 | 6.6 Score on a Scale STANDARD_DEVIATION 1.49 | 6.5 Score on a Scale STANDARD_DEVIATION 1.47 | 6.6 Score on a Scale STANDARD_DEVIATION 1.41 | — |
| WOMAC Physical Function Subscale Score | — | 6.42 Score on a Scale STANDARD_DEVIATION 1.602 | 6.47 Score on a Scale STANDARD_DEVIATION 1.583 | 6.56 Score on a Scale STANDARD_DEVIATION 1.631 | 6.41 Score on a Scale STANDARD_DEVIATION 1.495 | 6.27 Score on a Scale STANDARD_DEVIATION 1.699 | 6.38 Score on a Scale STANDARD_DEVIATION 1.598 | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 1,257 | 5 / 966 | 8 / 974 | 0 / 214 | 12 / 1,677 | 1 / 116 | 0 / 115 |
| other Total, other adverse events | 988 / 1,257 | 793 / 966 | 817 / 974 | 181 / 214 | 1,447 / 1,677 | 95 / 116 | 88 / 115 |
| serious Total, serious adverse events | 183 / 1,257 | 146 / 966 | 186 / 974 | 51 / 214 | 441 / 1,677 | 29 / 116 | 26 / 115 |
Outcome results
Primary
Change From Baseline to Week 16 in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score
The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations.
Time frame: Baseline to Week 16
Population: The full analysis set for the efficacy substudy (FAS-Substudy) included all randomized participants in the efficacy substudy. Here, Number of Participants Analyzed = Number of participants within a specified category.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Change From Baseline to Week 16 in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score | -1.55 Score on a Scale | Standard Error 0.178 |
| Fasinumab 1 mg SC Q8W | Change From Baseline to Week 16 in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score | -2.28 Score on a Scale | Standard Error 0.175 |
| Fasinumab 1 mg SC Q4W | Change From Baseline to Week 16 in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score | -2.77 Score on a Scale | Standard Error 0.171 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score | -2.78 Score on a Scale | Standard Error 0.174 |
| Fasinumab 6 mg SC Q8W | Change From Baseline to Week 16 in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score | -2.59 Score on a Scale | Standard Error 0.174 |
p-value: =0.00195% CI: [-1.159, -0.293]Mixed Models Analysis
p-value: <0.000195% CI: [-1.646, -0.793]Mixed Models Analysis
p-value: <0.000195% CI: [-1.664, -0.793]Mixed Models Analysis
p-value: <0.000195% CI: [-1.477, -0.606]Mixed Models Analysis
Primary
Change From Baseline to Week 16 in WOMAC Physical Function Subscale Score
The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations.
Time frame: Baseline to Week 16
Population: The full analysis set for the efficacy substudy (FAS-Substudy) included all randomized participants in the efficacy substudy. Here, Number of Participants Analyzed = Number of participants within a specified category.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Change From Baseline to Week 16 in WOMAC Physical Function Subscale Score | -1.35 Score on a Scale | Standard Error 0.177 |
| Fasinumab 1 mg SC Q8W | Change From Baseline to Week 16 in WOMAC Physical Function Subscale Score | -2.09 Score on a Scale | Standard Error 0.175 |
| Fasinumab 1 mg SC Q4W | Change From Baseline to Week 16 in WOMAC Physical Function Subscale Score | -2.55 Score on a Scale | Standard Error 0.173 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in WOMAC Physical Function Subscale Score | -2.61 Score on a Scale | Standard Error 0.177 |
| Fasinumab 6 mg SC Q8W | Change From Baseline to Week 16 in WOMAC Physical Function Subscale Score | -2.48 Score on a Scale | Standard Error 0.177 |
p-value: =0.000795% CI: [-1.163, -0.309]Mixed Models Analysis
p-value: <0.000195% CI: [-1.624, -0.768]Mixed Models Analysis
p-value: <0.000195% CI: [-1.698, -0.822]Mixed Models Analysis
p-value: <0.000195% CI: [-1.564, -0.695]Mixed Models Analysis
Primary
Number of Participants With Adjudicated Arthropathy (AA)
Adjudicated arthropathy (AA) is a composite term that encompasses the following conditions: Rapidly progressive OA type 1 and 2, Subchondral insufficiency fractures, and Primary Osteonecrosis. AAs were also evaluated to determine if they met Destructive Arthropathy criteria.
Time frame: Baseline up to week 52 and week 72
Population: The SAF-LTS included all randomized participants in the overall study who received any study drug; it was based on the treatment-as-received (as treated).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Adjudicated Arthropathy (AA) | Week 52 | 23 Participants |
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Adjudicated Arthropathy (AA) | Week 72 | 32 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Adjudicated Arthropathy (AA) | Week 72 | 71 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Adjudicated Arthropathy (AA) | Week 52 | 52 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) | Week 52 | 62 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) | Week 72 | 89 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) | Week 72 | 27 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) | Week 52 | 25 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Adjudicated Arthropathy (AA) | Week 52 | 238 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Adjudicated Arthropathy (AA) | Week 72 | 303 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) | Week 52 | 14 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) | Week 72 | 18 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) | Week 72 | 13 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) | Week 52 | 8 Participants |
Primary
Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria
DA is a unique clinical form of rapidly destructive arthropathy over and above that seen in the normal progression of OA. DA criteria can be associated with Rapidly Progressive OA type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee.
Time frame: Baseline up to week 52 and week 72
Population: The SAF-LTS included all randomized participants in the overall study who received any study drug; it was based on the treatment-as-received (as treated).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 52 | 0 Participants |
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 72 | 0 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 52 | 1 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 72 | 1 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 52 | 3 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 72 | 5 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 52 | 1 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 72 | 1 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 52 | 20 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 72 | 31 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 52 | 1 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 72 | 1 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 52 | 1 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria | Week 72 | 1 Participants |
Primary
Number of Participants With Anti-drug Antibody (ADA) up to Week 72
Immunogenicity was characterized by ADA responses & titers. Responses categories: Negative - ADA negative response at all time points, regardless of missing samples; Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses less than (\<) 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, greater than or equal to (≥) 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response in the fasinumab ADA assay post first dose when baseline results = negative or missing.
Time frame: Baseline up to week 72
Population: The ADA analysis set for the long-term safety population included all participants who received any study drug (SAF-LTS) and had at least 1 non-missing ADA result following the first dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | ADA Negative Status | 1115 Participants |
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Pre-existing Immunoreactivity | 22 Participants |
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Boosted Response | 0 Participants |
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Emergent Response | 16 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Boosted Response | 0 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | ADA Negative Status | 885 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Pre-existing Immunoreactivity | 16 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Emergent Response | 10 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Boosted Response | 0 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | ADA Negative Status | 907 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Emergent Response | 10 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Pre-existing Immunoreactivity | 12 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Emergent Response | 2 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Pre-existing Immunoreactivity | 6 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | ADA Negative Status | 200 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Boosted Response | 0 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | ADA Negative Status | 1547 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Pre-existing Immunoreactivity | 37 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Boosted Response | 0 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Emergent Response | 19 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Boosted Response | 0 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Pre-existing Immunoreactivity | 2 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | ADA Negative Status | 108 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Emergent Response | 1 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Boosted Response | 0 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Pre-existing Immunoreactivity | 1 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | Treatment-Emergent Response | 0 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Anti-drug Antibody (ADA) up to Week 72 | ADA Negative Status | 104 Participants |
Primary
Number of Participants With Any Adverse Event (AE) up to Week 72
Time frame: Baseline up to week 72
Population: The SAF-LTS included all randomized participants in the overall study who received any study drug; it was based on the treatment-as-received (as treated)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Any Adverse Event (AE) up to Week 72 | 1112 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Any Adverse Event (AE) up to Week 72 | 867 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Any Adverse Event (AE) up to Week 72 | 902 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Any Adverse Event (AE) up to Week 72 | 192 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Any Adverse Event (AE) up to Week 72 | 1570 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Any Adverse Event (AE) up to Week 72 | 106 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Any Adverse Event (AE) up to Week 72 | 106 Participants |
Primary
Number of Participants With Any Serious AE up to Week 72
Time frame: Baseline up to week 72
Population: The SAF-LTS included all randomized participants in the overall study who received any study drug; it was based on the treatment-as-received (as treated).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Any Serious AE up to Week 72 | 173 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Any Serious AE up to Week 72 | 138 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Any Serious AE up to Week 72 | 176 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Any Serious AE up to Week 72 | 44 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Any Serious AE up to Week 72 | 413 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Any Serious AE up to Week 72 | 28 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Any Serious AE up to Week 72 | 26 Participants |
Primary
Number of Participants With Any Serious TEAE
Time frame: Baseline up to week 52
Population: The SAF-LTS included all randomized participants in the overall study who received any study drug; it was based on the treatment-as-received (as treated).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Any Serious TEAE | 82 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Any Serious TEAE | 57 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Any Serious TEAE | 70 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Any Serious TEAE | 13 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Any Serious TEAE | 107 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Any Serious TEAE | 5 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Any Serious TEAE | 3 Participants |
Primary
Number of Participants With Any Treatment-Emergent Adverse Event (TEAE)
Time frame: Baseline up to week 52
Population: The safety analysis set for the evaluation of long-term safety (SAF-LTS) included all randomized participants in the overall study who received any study drug; it was based on the treatment-as-received (as treated).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) | 1055 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) | 840 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) | 885 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) | 185 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) | 1487 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) | 93 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) | 92 Participants |
Primary
Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery
All joint replacement surgery events regardless of cause at weeks 52 and 72. An end of study phone contact was also conducted approximately 52 weeks following the last dose of study drug.
Time frame: Baseline up to weeks 52, 72, and end of study (52 weeks post last dose)
Population: The SAF-LTS included all randomized participants in the overall study who received any study drug; it was based on the treatment-as-received (as treated).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | End of Study (52 weeks post-last dose) | 79 Participants |
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 72 | 55 Participants |
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 52 | 37 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 72 | 55 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 52 | 27 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | End of Study (52 weeks post-last dose) | 81 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | End of Study (52 weeks post-last dose) | 118 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 52 | 37 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 72 | 71 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 72 | 23 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 52 | 15 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | End of Study (52 weeks post-last dose) | 30 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 72 | 197 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 52 | 109 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | End of Study (52 weeks post-last dose) | 309 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 52 | 8 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | End of Study (52 weeks post-last dose) | 18 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 72 | 11 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | End of Study (52 weeks post-last dose) | 15 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 72 | 9 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery | Week 52 | 4 Participants |
Primary
Number of Participants With at Least One Peripheral Sensory Event That Required a Neurology Consultation
Any participant with a peripheral sensory event that persisted for 2 months was referred for a neurology or other specialty consultation and reported as an adverse event of special interest (AESI).
Time frame: Baseline up to week 72
Population: The SAF-LTS included all randomized participants in the overall study who received any study drug; it was based on the treatment-as-received (as treated).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With at Least One Peripheral Sensory Event That Required a Neurology Consultation | 29 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With at Least One Peripheral Sensory Event That Required a Neurology Consultation | 65 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With at Least One Peripheral Sensory Event That Required a Neurology Consultation | 62 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With at Least One Peripheral Sensory Event That Required a Neurology Consultation | 21 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With at Least One Peripheral Sensory Event That Required a Neurology Consultation | 75 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With at Least One Peripheral Sensory Event That Required a Neurology Consultation | 3 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With at Least One Peripheral Sensory Event That Required a Neurology Consultation | 1 Participants |
Primary
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72
Number of participants with potentially clinically significant abnormal values in hematology, chemistry, and urinalysis during the post-treatment period were reported. Clinical significance was determined by the investigator.
Time frame: End of treatment up to week 72
Population: The SAF-LTS included all randomized participants in the overall study who received any study drug; it was based on the treatment-as-received (as treated).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Chemistry | 267 Participants |
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Hematology | 171 Participants |
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Urinalysis | 16 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Chemistry | 228 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Hematology | 149 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Urinalysis | 24 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Chemistry | 225 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Hematology | 154 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Urinalysis | 18 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Hematology | 23 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Urinalysis | 1 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Chemistry | 59 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Chemistry | 474 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Hematology | 279 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Urinalysis | 37 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Hematology | 29 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Chemistry | 36 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Urinalysis | 5 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Chemistry | 40 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Hematology | 32 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72 | Urinalysis | 3 Participants |
Primary
Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52
Number of participants with potentially clinically significant abnormal values in hematology, chemistry, and urinalysis during the treatment period were reported. Clinical significance was determined by the investigator.
Time frame: Baseline to week 52
Population: The SAF-LTS included all randomized participants in the overall study who received any study drug; it was based on the treatment-as-received (as treated).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Urinalysis | 32 Participants |
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Chemistry | 403 Participants |
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Hematology | 195 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Chemistry | 365 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Hematology | 236 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Urinalysis | 42 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Urinalysis | 45 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Hematology | 241 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Chemistry | 403 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Chemistry | 105 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Hematology | 28 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Urinalysis | 2 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Chemistry | 717 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Hematology | 304 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Urinalysis | 55 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Hematology | 7 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Urinalysis | 1 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Chemistry | 36 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Urinalysis | 1 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Chemistry | 34 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52 | Hematology | 11 Participants |
Primary
Number of Participants With Sympathetic Nervous System (SNS) Dysfunction
Potential events of sympathetic nervous system (SNS) dysfunction were monitored throughout the study through physical examination, AE reporting, assessment of orthostatic hypotension, and the Survey of Autonomic Symptoms. Sympathetic nervous system dysfunction was diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist.
Time frame: Baseline up to week 72
Population: The SAF-LTS included all randomized participants in the overall study who received any study drug; it was based on the treatment-as-received (as treated).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With Sympathetic Nervous System (SNS) Dysfunction | 0 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With Sympathetic Nervous System (SNS) Dysfunction | 0 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Sympathetic Nervous System (SNS) Dysfunction | 0 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With Sympathetic Nervous System (SNS) Dysfunction | 0 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With Sympathetic Nervous System (SNS) Dysfunction | 1 Participants |
| Fasinumab 6 mg SC Q4W | Number of Participants With Sympathetic Nervous System (SNS) Dysfunction | 0 Participants |
| Fasinumab 9 mg SC Q4W | Number of Participants With Sympathetic Nervous System (SNS) Dysfunction | 0 Participants |
Secondary
Change From Baseline to Week 16 in Patient Global Assessment (PGA) Score of Osteoarthritis
The PGA of OA is a patient-rated assessment of current disease state on a 5-point Likert scale (1 = very good; 2 = good; 3 = fair; 4 = poor; and 5 = very poor).
Time frame: Baseline to Week 16
Population: The full analysis set for the efficacy substudy (FAS-Substudy) included all randomized participants in the efficacy substudy. Here, Number of Participants Analyzed = Number of participants within a specified category.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Change From Baseline to Week 16 in Patient Global Assessment (PGA) Score of Osteoarthritis | -0.66 Score on a Scale | Standard Error 0.07 |
| Fasinumab 1 mg SC Q8W | Change From Baseline to Week 16 in Patient Global Assessment (PGA) Score of Osteoarthritis | -0.87 Score on a Scale | Standard Error 0.071 |
| Fasinumab 1 mg SC Q4W | Change From Baseline to Week 16 in Patient Global Assessment (PGA) Score of Osteoarthritis | -0.93 Score on a Scale | Standard Error 0.069 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in Patient Global Assessment (PGA) Score of Osteoarthritis | -0.99 Score on a Scale | Standard Error 0.071 |
| Fasinumab 6 mg SC Q8W | Change From Baseline to Week 16 in Patient Global Assessment (PGA) Score of Osteoarthritis | -0.96 Score on a Scale | Standard Error 0.072 |
p-value: =0.02395% CI: [-0.38, -0.028]Mixed Models Analysis
p-value: =0.002595% CI: [-0.437, -0.093]Mixed Models Analysis
p-value: =0.000395% CI: [-0.496, -0.145]Mixed Models Analysis
p-value: =0.00195% CI: [-0.466, -0.118]Mixed Models Analysis
Secondary
Number of Participants With ≥30% Reduction From Baseline to Week 16 in the WOMAC Pain Subscale Score
The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. Participants who achieved a response, where response was defined as an improvement by ≥30% in WOMAC pain subscale score
Time frame: Baseline to Week 16
Population: The full analysis set for the efficacy substudy (FAS-Substudy) included all randomized participants in the efficacy substudy. Here, Number of Participants Analyzed = Number of participants within a specified category. Participants with missing data are considered as a non-response.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fasinumab-matching Placebo Q4W/Q8W | Number of Participants With ≥30% Reduction From Baseline to Week 16 in the WOMAC Pain Subscale Score | 76 Participants |
| Fasinumab 1 mg SC Q8W | Number of Participants With ≥30% Reduction From Baseline to Week 16 in the WOMAC Pain Subscale Score | 108 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With ≥30% Reduction From Baseline to Week 16 in the WOMAC Pain Subscale Score | 126 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With ≥30% Reduction From Baseline to Week 16 in the WOMAC Pain Subscale Score | 118 Participants |
| Fasinumab 6 mg SC Q8W | Number of Participants With ≥30% Reduction From Baseline to Week 16 in the WOMAC Pain Subscale Score | 114 Participants |