Pigmented Villonodular Synovitis, PVNS, Giant Cell Tumor of the Tendon Sheath, GCCTS, Tenosynovial Giant Cell Tumor Localized or Diffused Type, GCTS
Conditions
Keywords
Pigmented Villonodular Synovitis, PVNS, Giant cell tumor of the tendon sheath, GCCTS, Tenosynovial giant cell tumor (localized or diffused type), GCTS, MCS110
Brief summary
This study, designed as a proof of concept study of MCS110 in pigmented villonodular synovitis, assessed the clinical response to MCS110 treatment in Pigmented Villonodular Synovitis (PVNS) patients, after a single or multiple intravenous doses of MCS110, using magnetic resonance imaging to assess tumor volume, and evaluated the pharmacokinetics/pharmacodynamics, safety and tolerability in this population.
Interventions
DRUGMCS110
Patients will receive up to 6 doses of MCS110 (3 or 5 or 10mg/kg) administered intravenously once every 4 weeks. Before each dosing, safety will be assessed.
DRUGPlacebo
Participants will receive a single dose of NaCl on day 1 through intravenous infusion.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and Females aged ≥ 18 years (≥ 12 years in PART C) with PVNS or GCTTS with, at least, one measurable site of disease on MRI. * Patients expected to get surgery (PART A of study only). * Vital signs within the ranges: systolic blood pressure 80-150 mmHg , diastolic blood pressure 50-100 mmHg, pulse rate 40-100 bpm, oral body temperature 35.0-37.5°C. * Patients with normal level of serum ionized calcium and phosphate. * Women of child-bearing potential must use highly effective contraception during the study and for 84 days after the study drug infusion.
Exclusion criteria
* Patients with major surgery less than 3 months prior to start study drug or who have still side effects of such therapy. * Presence of systemic illness precluding definitive surgery or increasing the risk to patients due to potential immunosuppression. * Use previously of intra-articular treatment within 4 weeks prior dosing. * Patients with dermal change indicative of lymphedema or phlebolymphedema. disease. * Patients with elevated troponin T and/or CK levels (\> 1.5 x ULN for the laboratory) or with history of myositis, rhabdomyolysis or other myopathic disease. * Patients receiving immunosuppressive treatment as well as corticosteroids which cannot be discontinued at least 4 weeks before dosing. * Patients engaged in a resistance exercise training program. * Patients with pacemakers or any metallic objects as exclusion for MRI * Patients with concomitant disease know to get influence on bone metabolism * Patients who have history of drug or alcohol abuse within 12 months prior study dosing. * Pregnant or nursing (lactating) women. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size | Week 4 | To assess the efficacy of a single i.v. dose of MCS110 in changing the size of PVNS tumors (as compared to baseline) compared to placebo over 4 weeks evaluated by volume of PVNS tumors by 3-dimensional MRI. This analysis includes all data from patients 4 weeks after receiving the first dose of MCS110 (3, 5 or 10 mg/kg) or placebo and assesses the tumor volume changes at week 4 as compared to baseline. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called ABC4. |
| Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size | Week 4 | To assess the efficacy of a single i.v. dose of MCS110 in percent change of the PVNS tumor volume at week 4 as compared to baseline and compared to placebo evaluated by volume of PVNS tumors by 3-dimensional MRI. This analysis includes all data from patients who received at least a single dose of MCS110 (3, 5 or 10 mg/kg) or placebo and assesses the tumor volume changes at week 4 as compared to baseline. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called ABC4. |
| Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | Up to 8 weeks post last dose | Assessment of maximum efficacy (multiple i.v.monthly doses (2 to 6) of 3, 5 or 10 mg/kg MCS110 or 3 & 10 mg/kg or 5 & 10 mg/kg in changing PVNS tumor volume (as compared to baseline) up to 8 weeks post last dose evaluated by MRI. Analysis included data starting from 1st dose of MCS110 in all treatment groups of Parts B and C. Part B patients who received placebo as 1st dose, measurement prior to receiving first dose of MCS110, was used as baseline and assessment time-points were adjusted accordingly. For Part C, participants starting treatment with low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and tumor volume reduction was ≤ 45%. Analysis includes data from patients who received at least 2 doses. The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg \[3/10 mg/kg\] or after 3 doses of 5 mg/kg to 10 mg/kg \[5/10 mg/kg\] |
| Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | Up to 8 weeks post last dose | To assess the maximum efficacy of multiple monthly i.v. doses (2 to 6) of 3, 5 or 10 mg/kg MCS110 or 3 and 10 mg/kg or 5 and 10 mg/kg by percent change in the PVNS tumor volume (as compared to baseline) up to 8 weeks post last dose evaluated by MRI. Subjects starting treatment with a low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and the tumor volume reduction was ≤ 45%. This analysis includes data from all participants who received at least 2 doses of MCS110 and thus includes only patients from Part B and C of the study, thus the data set is called Part BC. The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg \[3/10 mg/kg\] or after 3 doses of 5 mg/kg to 10 mg/kg \[5/10 mg/kg\]. |
| Number of Participants With Adverse Events | Approximately 2 years | Overall incidence of Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Negative Anti-MCS110 Antibody | Baseline, throughout the study up to Day 505 | To assess the immunogenicity of MCS110 in serum anti-MCS110 antibody concentrations |
| Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 4 | To assess the clinical response of joint range of motion following a single i.v. dose of MCS110 or placebo as compared to baseline 4 weeks post-dose evaluated in participants, who had a knee tumor, which was the majority of participants (75%). The analysis includes all data from patients 4 weeks after receiving the first dose of MCS110 (3, 5 or 10 mg/kg) or placebo. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called ABC4. |
| Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Baseline, Week 4, Week 12, Week 24, Week 28, Week 40, Week 48, Week 104 | Measurement of the participant's pain with a 100 mm visual analog scale (VAS) following treatment with MCS110 3, 5, or 10 mg/kg evaluated. Data presented are changes from baseline in degree. Participants were asked to place a line perpendicular to the VAS line at the point that represented her/his pain intensity. Using a ruler, the score was determined by measuring the distance (mm) on the 10-cm line between the no pain anchor and the participants mark, providing a score from 0-100. Analysis includes data from participants with knee tumor who received at least 2 doses of MCS110 and thus includes only patients from Part B and C of the study, thus the data set is called Part BC. The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg \[3/10 mg/kg\] or after 3 doses of 5 mg/kg to 10 mg/kg \[5/10 mg/kg\]. |
| Time to Relapse | Up to Week 104 | Time to relapse describes the time frame from baseline when the tumor volume increases again after the treatment with MCS110. To be considered a relapse tumor volume had to increase greater than 50% of the difference between tumor volume at baseline and the lowest tumor volume measured by MRI. In this assessment the Part B and Part C patients were analyzed separately. N/A (not available):Data analysis not performed as sample size was not analyzable as no patient had surgery/relapse. |
| Time to Surgery | Up to Week 104 | Time to surgery describes the time frame from baseline to the time point when participants had surgical removement of PVNS tumor. This could be either residual tumor after the tumor volume was reduced or surgery due to relapse. In this assessment the Part B and Part C patients were analyzed separately. Not Available (NA): Data analysis not performed as sample size was not analyzable as no patient had surgery. |
| Average of Health-Related Quality of Life Questionnaire Score for mHAQ | up to 104 weeks | The mHAQ assesses 20 activities in 8 categories related to daily life, which are rated on a 4-point Likert scale. The mHAQ is calculated as the average of the single scores with the following scoring: without difficulty =0; with some difficulty =1; with much difficulty =2; unable to do =3. Total score is between 0 - 3.0. Values \<0.3 are considered normal. Data presented include only participants, who received multiple doses of MCS110. |
| Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC) | Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr) | Pharmacokinetic for a single dose of MCS110 for serum concentration -time curve (AUC). |
| Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study) | The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life (QOL), pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor. |
| Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study) | The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life, pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor. |
| Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study) | The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life, pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor. |
| Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study) | The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life, pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor. |
| Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study) | The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life, pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor. |
| Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Week 4, Week 24, up to 104 weeks | The EQ-5D is a standardized measure of health status. The EQ visual analogue scale (EQ VAS)has a range from 0-100: worst possible to perfect health. Data show the absolute change from baseline of EQ5D VAS and at the different visits for participants, who received multiple doses of MCS110. (PART B and PART C). |
| Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes | Baseline Up to Week 104 | Blood samples were collected for the evaluation of CD14+ monocytes (using FACS) and CD14+ CD16+ monocytes. Based on preliminary analysis, the quality of the samples did not allow meaningful conclusions to be drawn. Thus, in Part B, the monocyte sample collection was discontinued. |
| Pharmacokinetics of MCS110 Maximum Concentration (Cmax) | Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr) | Pharmacokinetic characterization of a single dose of MCS110 for maximum serum concentration (Cmax) |
| Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax) | Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr) | Pharmacokinetic characterization of a single dose of MCS110 for time to maximum concentration (Tmax) |
| Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Baseline, Day 1, Day 85, Day 169 | Pharmacokinetic characterization of a single dose of MCS110 for evaluation of macrophage-colony stimulating factor (M-CSF) plasma concentrations over time |
| Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I). | Baseline, Week 4, Week 24, Week 104 | Pharmacodynamic characterization of a single dose of MCS110 by measuring C-terminal telopeptide of Type 1 Collagen peptide (CTX-I), a biomarker of bone resorption. Data measured in participants from three arms: participants from Part A, B and C who received a single dose of 10 mg/kg and had assessment at week 4 (Part ABC4); participants from Part A and B who received placebo ; and participants from Part B and C who received multiple monthly doses of MCS110 (10 mg/kg.) Serum CTX-I data were generated in Part A and Part B. In Part C, samples were collected for serum bone CTX-I analysis. The analysis was not performed, as enough information on compound mode of action was obtained using creatine kinase (CK) and monocytes (hematology) data. Only data from 10mg/kg (single and multiple doses) are available. |
Countries
Switzerland, United States
Participant flow
Recruitment details
Thirty-seven subjects diagnosed with PVNS or GCTTS were evaluated as part of this study. In all, 36 subjects were treated in three parts (Parts A, B and C) of the study, 30 of whom completed the study. At this final analysis, 6 treated subjects had discontinued from the study.
Participants by arm
| Arm | Count |
|---|---|
| MCS110 10 mg/kg (PART A) Participants received a single dose of 10 mg/kg on Day 1 administered by i.v. infusion | 5 |
| Placebo (PART A) Participants received single dose placebo by i.v. infusion to match MCS110 10 mg/kg | 2 |
| MCS110 10 mg/kg (PART B) Participants received multiple monthly doses of MCS110 10 mg/kg. This group also included participants who had received placebo as a 1st dose | 8 |
| Placebo/10mg/kg (PART B) Participants received single dose placebo to match first dose of MCS110 10 mg/kg and then continued with monthly administration of MCS110 10 mg/kg. fter this first single dose of placebo participants switched to monthly administration of MCS110 10 mg/kg and were added to the MCS110 10 mg/kg (PART B) group, which then increased from 8 to 11 participants. Participants could have received a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor grew again | 3 |
| MCS110 3 mg/kg (Part C) Participants received multiple monthly doses of MCS110 3 mg/kg. Participants could have received a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor grew again | 3 |
| MCS110 5 mg/kg (Part C) Participants received multiple monthly doses of MCS110 5 mg/kg. Participants could have received a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor grew again | 3 |
| MCS110 10 mg/kg (Part C) Participants received multiple monthly doses of MCS110 10 mg/kg. Participants could have received a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor grew again | 4 |
| MCS110 3 mg/kg & MCS110 10mg/kg (Part C) Participants received 3 doses of 3 mg/kg and if not efficacious (≥45% of tumor volume reduction) could switch to 10 mg/kg. This is a subset of participants who started with a dose of 3 mg/kg. Participants could have received a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor grew again. | 4 |
| MCS110 5 mg/kg & MCS110 10mg/kg (PART C) Participants received 3 doses of 5 mg/kg and if not efficacious (≥45% of tumor volume reduction) could switch to 10 mg/kg. This is a subset of participants who started with a dose of 5 mg/kg. Participants could have received a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor grew again. | 4 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Administrative Problems | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | MCS110 10 mg/kg (PART A) | Placebo (PART A) | MCS110 10 mg/kg (PART B) | Placebo/10mg/kg (PART B) | MCS110 3 mg/kg (Part C) | MCS110 5 mg/kg (Part C) | MCS110 10 mg/kg (Part C) | MCS110 3 mg/kg & MCS110 10mg/kg (Part C) | MCS110 5 mg/kg & MCS110 10mg/kg (PART C) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 51.4 Years STANDARD_DEVIATION 8.96 | 30.0 Years STANDARD_DEVIATION 4.24 | 46.3 Years STANDARD_DEVIATION 10.14 | 26.7 Years STANDARD_DEVIATION 11.59 | 45.7 Years STANDARD_DEVIATION 17.93 | 38.0 Years STANDARD_DEVIATION 21.66 | 43.8 Years STANDARD_DEVIATION 13.38 | 46.3 Years STANDARD_DEVIATION 2.87 | 29.0 Years STANDARD_DEVIATION 6.06 | 41.3 Years STANDARD_DEVIATION 12.91 |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 4 Participants | 1 Participants | 8 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 31 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 6 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 22 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 14 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 | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 2 | 0 / 11 | 0 / 3 | 0 / 7 | 0 / 7 | 0 / 12 |
| other Total, other adverse events | 3 / 5 | 1 / 2 | 11 / 11 | 3 / 3 | 7 / 7 | 6 / 7 | 11 / 12 |
| serious Total, serious adverse events | 0 / 5 | 1 / 2 | 2 / 11 | 0 / 3 | 3 / 7 | 1 / 7 | 4 / 12 |
Outcome results
Primary
Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size
Assessment of maximum efficacy (multiple i.v.monthly doses (2 to 6) of 3, 5 or 10 mg/kg MCS110 or 3 & 10 mg/kg or 5 & 10 mg/kg in changing PVNS tumor volume (as compared to baseline) up to 8 weeks post last dose evaluated by MRI. Analysis included data starting from 1st dose of MCS110 in all treatment groups of Parts B and C. Part B patients who received placebo as 1st dose, measurement prior to receiving first dose of MCS110, was used as baseline and assessment time-points were adjusted accordingly. For Part C, participants starting treatment with low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and tumor volume reduction was ≤ 45%. Analysis includes data from patients who received at least 2 doses. The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg \[3/10 mg/kg\] or after 3 doses of 5 mg/kg to 10 mg/kg \[5/10 mg/kg\]
Time frame: Up to 8 weeks post last dose
Population: Pharmacodynamic Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PART ABC4) | Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | -2450.3 mm3 | Standard Deviation 2721.24 |
| MCS110 3 mg/kg (PART ABC4) | Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | -29164.3 mm3 | Standard Deviation 23286.18 |
| MCS110 5 mg/kg (PART ABC4) | Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | -37015.1 mm3 | Standard Deviation 29297.02 |
| MCS110 10 mg/kg (PART ABC4) | Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | -42420.1 mm3 | Standard Deviation 63812.69 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | -3571.9 mm3 | Standard Deviation 3612.97 |
Primary
Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size
To assess the efficacy of a single i.v. dose of MCS110 in changing the size of PVNS tumors (as compared to baseline) compared to placebo over 4 weeks evaluated by volume of PVNS tumors by 3-dimensional MRI. This analysis includes all data from patients 4 weeks after receiving the first dose of MCS110 (3, 5 or 10 mg/kg) or placebo and assesses the tumor volume changes at week 4 as compared to baseline. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called ABC4.
Time frame: Week 4
Population: Pharmacodynamic Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PART ABC4) | Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size | -4222.8 mm3 | Standard Deviation 6284.56 |
| MCS110 3 mg/kg (PART ABC4) | Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size | -668.5 mm3 | Standard Deviation 18751.44 |
| MCS110 5 mg/kg (PART ABC4) | Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size | -9998.4 mm3 | Standard Deviation 15628.4 |
| MCS110 10 mg/kg (PART ABC4) | Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size | -38002.1 mm3 | Standard Deviation 57314.73 |
Primary
Number of Participants With Adverse Events
Overall incidence of Adverse Events
Time frame: Approximately 2 years
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (PART ABC4) | Number of Participants With Adverse Events | AEs leading to discontinuation | 0 Participants |
| Placebo (PART ABC4) | Number of Participants With Adverse Events | Serious AEs | 0 Participants |
| Placebo (PART ABC4) | Number of Participants With Adverse Events | AEs of mild severity | 3 Participants |
| Placebo (PART ABC4) | Number of Participants With Adverse Events | AEs of moderate severity | 1 Participants |
| Placebo (PART ABC4) | Number of Participants With Adverse Events | AEs of severe severity | 0 Participants |
| Placebo (PART ABC4) | Number of Participants With Adverse Events | Study drug related AEs | 3 Participants |
| MCS110 3 mg/kg (PART ABC4) | Number of Participants With Adverse Events | AEs of severe severity | 0 Participants |
| MCS110 3 mg/kg (PART ABC4) | Number of Participants With Adverse Events | AEs of mild severity | 1 Participants |
| MCS110 3 mg/kg (PART ABC4) | Number of Participants With Adverse Events | AEs leading to discontinuation | 0 Participants |
| MCS110 3 mg/kg (PART ABC4) | Number of Participants With Adverse Events | Serious AEs | 1 Participants |
| MCS110 3 mg/kg (PART ABC4) | Number of Participants With Adverse Events | AEs of moderate severity | 1 Participants |
| MCS110 3 mg/kg (PART ABC4) | Number of Participants With Adverse Events | Study drug related AEs | 1 Participants |
| MCS110 5 mg/kg (PART ABC4) | Number of Participants With Adverse Events | AEs leading to discontinuation | 0 Participants |
| MCS110 5 mg/kg (PART ABC4) | Number of Participants With Adverse Events | Serious AEs | 2 Participants |
| MCS110 5 mg/kg (PART ABC4) | Number of Participants With Adverse Events | Study drug related AEs | 10 Participants |
| MCS110 5 mg/kg (PART ABC4) | Number of Participants With Adverse Events | AEs of severe severity | 4 Participants |
| MCS110 5 mg/kg (PART ABC4) | Number of Participants With Adverse Events | AEs of mild severity | 11 Participants |
| MCS110 5 mg/kg (PART ABC4) | Number of Participants With Adverse Events | AEs of moderate severity | 9 Participants |
| MCS110 10 mg/kg (PART ABC4) | Number of Participants With Adverse Events | AEs of mild severity | 1 Participants |
| MCS110 10 mg/kg (PART ABC4) | Number of Participants With Adverse Events | AEs of moderate severity | 2 Participants |
| MCS110 10 mg/kg (PART ABC4) | Number of Participants With Adverse Events | AEs of severe severity | 0 Participants |
| MCS110 10 mg/kg (PART ABC4) | Number of Participants With Adverse Events | Study drug related AEs | 1 Participants |
| MCS110 10 mg/kg (PART ABC4) | Number of Participants With Adverse Events | Serious AEs | 0 Participants |
| MCS110 10 mg/kg (PART ABC4) | Number of Participants With Adverse Events | AEs leading to discontinuation | 0 Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Adverse Events | AEs of severe severity | 2 Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Adverse Events | Study drug related AEs | 7 Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Adverse Events | AEs of moderate severity | 4 Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Adverse Events | AEs leading to discontinuation | 2 Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Adverse Events | Serious AEs | 3 Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Adverse Events | AEs of mild severity | 7 Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Adverse Events | AEs of severe severity | 1 Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Adverse Events | AEs of moderate severity | 2 Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Adverse Events | AEs leading to discontinuation | 1 Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Adverse Events | AEs of mild severity | 6 Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Adverse Events | Study drug related AEs | 5 Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Adverse Events | Serious AEs | 1 Participants |
| MCS110 10 mg/kg (PART C) | Number of Participants With Adverse Events | Study drug related AEs | 8 Participants |
| MCS110 10 mg/kg (PART C) | Number of Participants With Adverse Events | AEs of mild severity | 11 Participants |
| MCS110 10 mg/kg (PART C) | Number of Participants With Adverse Events | AEs of severe severity | 4 Participants |
| MCS110 10 mg/kg (PART C) | Number of Participants With Adverse Events | Serious AEs | 4 Participants |
| MCS110 10 mg/kg (PART C) | Number of Participants With Adverse Events | AEs of moderate severity | 5 Participants |
| MCS110 10 mg/kg (PART C) | Number of Participants With Adverse Events | AEs leading to discontinuation | 1 Participants |
Primary
Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size
To assess the maximum efficacy of multiple monthly i.v. doses (2 to 6) of 3, 5 or 10 mg/kg MCS110 or 3 and 10 mg/kg or 5 and 10 mg/kg by percent change in the PVNS tumor volume (as compared to baseline) up to 8 weeks post last dose evaluated by MRI. Subjects starting treatment with a low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and the tumor volume reduction was ≤ 45%. This analysis includes data from all participants who received at least 2 doses of MCS110 and thus includes only patients from Part B and C of the study, thus the data set is called Part BC. The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg \[3/10 mg/kg\] or after 3 doses of 5 mg/kg to 10 mg/kg \[5/10 mg/kg\].
Time frame: Up to 8 weeks post last dose
Population: Pharmacodynamic Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PART ABC4) | Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | -29.7 Percentage | Standard Deviation 33.73 |
| MCS110 3 mg/kg (PART ABC4) | Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | -56.3 Percentage | Standard Deviation 20.31 |
| MCS110 5 mg/kg (PART ABC4) | Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | -55.0 Percentage | Standard Deviation 19.02 |
| MCS110 10 mg/kg (PART ABC4) | Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | -45.8 Percentage | Standard Deviation 40.11 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | -22.6 Percentage | Standard Deviation 16.21 |
Primary
Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size
To assess the efficacy of a single i.v. dose of MCS110 in percent change of the PVNS tumor volume at week 4 as compared to baseline and compared to placebo evaluated by volume of PVNS tumors by 3-dimensional MRI. This analysis includes all data from patients who received at least a single dose of MCS110 (3, 5 or 10 mg/kg) or placebo and assesses the tumor volume changes at week 4 as compared to baseline. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called ABC4.
Time frame: Week 4
Population: Pharmacodynamic Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PART ABC4) | Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size | -7.7 Percentage | Standard Deviation 5.1 |
| MCS110 3 mg/kg (PART ABC4) | Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size | -7.4 Percentage | Standard Deviation 13.21 |
| MCS110 5 mg/kg (PART ABC4) | Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size | -24.8 Percentage | Standard Deviation 23.42 |
| MCS110 10 mg/kg (PART ABC4) | Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size | -32.6 Percentage | Standard Deviation 16.61 |
p-value: 0.91595% CI: [0.71, 1.36]ANCOVA
p-value: 0.11795% CI: [0.57, 1.07]ANCOVA
p-value: 0.0195% CI: [0.52, 0.91]ANCOVA
Secondary
Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion
To assess the clinical response of joint range of motion following multiple dose treatment with MCS110 3, 5, or 10 mg/kg evaluated in participants with knee tumor, which was the majority of participants (75%). The data presented are changes from baseline in degree. Participants, who started treatment with a low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and the tumor volume reduction was ≤ 45%. This analysis includes data from participants with knee tumor who received at least 2 doses of MCS110 and thus includes only patients from Part B and C of the study, thus the data set is called Part BC. The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg \[3/10 mg/kg\] or after 3 doses of 5 mg/kg to 10 mg/kg \[5/10 mg/kg\].
Time frame: Week 24/28, Week 104
Population: Pharmacodynamic analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 24/28: Knee extension | -10.0 Degree | Standard Deviation 0 |
| Placebo (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 24/28:(Knee Flexion) | -2.0 Degree | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 24/28:(Knee Flexion) | 8 Degree | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 104: (Knee Flexion) | -6 Degree | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 104:(Knee Extension) | 0 Degree | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 24/28: Knee extension | 0.0 Degree | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 24/28:(Knee Flexion) | 9.9 Degree | Standard Deviation 8.77 |
| MCS110 5 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 104: (Knee Flexion) | 7.5 Degree | Standard Deviation 11.56 |
| MCS110 5 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 24/28: Knee extension | -10.5 Degree | Standard Deviation 21.36 |
| MCS110 5 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 104:(Knee Extension) | -3.5 Degree | Standard Deviation 6.07 |
| MCS110 10 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 104: (Knee Flexion) | 10 Degree | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 24/28: Knee extension | -26 Degree | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 24/28:(Knee Flexion) | 8 Degree | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 104:(Knee Extension) | -28.0 Degree | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 104: (Knee Flexion) | 70.0 Degree | Standard Deviation 70.71 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 24/28: Knee extension | 1 Degree | Standard Deviation 1.73 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 24/28:(Knee Flexion) | 53.0 Degree | Standard Deviation 61.54 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Week 104:(Knee Extension) | 2.5 Degree | Standard Deviation 3.54 |
Secondary
Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion
To assess the clinical response of joint range of motion following a single i.v. dose of MCS110 or placebo as compared to baseline 4 weeks post-dose evaluated in participants, who had a knee tumor, which was the majority of participants (75%). The analysis includes all data from patients 4 weeks after receiving the first dose of MCS110 (3, 5 or 10 mg/kg) or placebo. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called ABC4.
Time frame: Week 4
Population: Pharmacodynamic Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Knee Extension | -7.3 Degree | Standard Deviation 4.99 |
| Placebo (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Knee Flexion | -2.8 Degree | Standard Deviation 8.85 |
| MCS110 3 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Knee Flexion | 3.7 Degree | Standard Deviation 13.5 |
| MCS110 3 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Knee Extension | -12.3 Degree | Standard Deviation 13.65 |
| MCS110 5 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Knee Extension | 1.7 Degree | Standard Deviation 2.89 |
| MCS110 5 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Knee Flexion | 13.7 Degree | Standard Deviation 19.76 |
| MCS110 10 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Knee Extension | -10.3 Degree | Standard Deviation 26.69 |
| MCS110 10 mg/kg (PART ABC4) | Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion | Knee Flexion | -15.4 Degree | Standard Deviation 43.13 |
Secondary
Average of Health-Related Quality of Life Questionnaire Score for mHAQ
The mHAQ assesses 20 activities in 8 categories related to daily life, which are rated on a 4-point Likert scale. The mHAQ is calculated as the average of the single scores with the following scoring: without difficulty =0; with some difficulty =1; with much difficulty =2; unable to do =3. Total score is between 0 - 3.0. Values \<0.3 are considered normal. Data presented include only participants, who received multiple doses of MCS110.
Time frame: up to 104 weeks
Population: Pharmacodynamic analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Average of Health-Related Quality of Life Questionnaire Score for mHAQ | Baseline | 0.3 Scores on a scale | Standard Deviation 0.35 |
| MCS110 3 mg/kg (PART ABC4) | Average of Health-Related Quality of Life Questionnaire Score for mHAQ | Week 104 | 0.1 Scores on a scale | Standard Deviation 0.14 |
| MCS110 3 mg/kg (PART ABC4) | Average of Health-Related Quality of Life Questionnaire Score for mHAQ | Baseline | 0.1 Scores on a scale | Standard Deviation 0.22 |
| MCS110 5 mg/kg (PART ABC4) | Average of Health-Related Quality of Life Questionnaire Score for mHAQ | Week 104 | 0.2 Scores on a scale | Standard Deviation 0.18 |
| MCS110 5 mg/kg (PART ABC4) | Average of Health-Related Quality of Life Questionnaire Score for mHAQ | Baseline | 0.3 Scores on a scale | Standard Deviation 0.2 |
| MCS110 10 mg/kg (PART ABC4) | Average of Health-Related Quality of Life Questionnaire Score for mHAQ | Baseline | 0.3 Scores on a scale | Standard Deviation 0.33 |
| MCS110 10 mg/kg (PART ABC4) | Average of Health-Related Quality of Life Questionnaire Score for mHAQ | Week 104 | 0.1 Scores on a scale | Standard Deviation 0.19 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Average of Health-Related Quality of Life Questionnaire Score for mHAQ | Week 104 | 0.3 Scores on a scale | Standard Deviation 0.25 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Average of Health-Related Quality of Life Questionnaire Score for mHAQ | Baseline | 0.9 Scores on a scale | Standard Deviation 0.52 |
Secondary
Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS)
Measurement of the participant's pain with a 100 mm visual analog scale (VAS) following treatment with MCS110 3, 5, or 10 mg/kg evaluated. Data presented are changes from baseline in degree. Participants were asked to place a line perpendicular to the VAS line at the point that represented her/his pain intensity. Using a ruler, the score was determined by measuring the distance (mm) on the 10-cm line between the no pain anchor and the participants mark, providing a score from 0-100. Analysis includes data from participants with knee tumor who received at least 2 doses of MCS110 and thus includes only patients from Part B and C of the study, thus the data set is called Part BC. The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg \[3/10 mg/kg\] or after 3 doses of 5 mg/kg to 10 mg/kg \[5/10 mg/kg\].
Time frame: Baseline, Week 4, Week 12, Week 24, Week 28, Week 40, Week 48, Week 104
Population: Pharmacodynamic analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 24 | 0 millimeters (mm) | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 12 | 20 millimeters (mm) | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 104 | 0 millimeters (mm) | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 48 | 0 millimeters (mm) | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 40 | 31 millimeters (mm) | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 4 | 22.5 millimeters (mm) | Standard Deviation 20.51 |
| Placebo (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Baseline | 32 millimeters (mm) | Standard Deviation 4.24 |
| Placebo (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 28 | 40 millimeters (mm) | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 48 | 0 millimeters (mm) | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 104 | 16.0 millimeters (mm) | Standard Deviation 18.03 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 12 | 2.7 millimeters (mm) | Standard Deviation 3.06 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 24 | 0 millimeters (mm) | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Baseline | 9.3 millimeters (mm) | Standard Deviation 12.74 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 28 | 10.7 millimeters (mm) | Standard Deviation 17.62 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 40 | 3.7 millimeters (mm) | Standard Deviation 5.51 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 4 | 4 millimeters (mm) | Standard Deviation 5.29 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 40 | 31.0 millimeters (mm) | Standard Deviation 31.38 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Baseline | 28.6 millimeters (mm) | Standard Deviation 21.82 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 4 | 22.5 millimeters (mm) | Standard Deviation 23.87 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 104 | 22.4 millimeters (mm) | Standard Deviation 24.23 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 12 | 13.9 millimeters (mm) | Standard Deviation 16.01 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 48 | 21.0 millimeters (mm) | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 28 | 0 millimeters (mm) | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 24 | 21.4 millimeters (mm) | Standard Deviation 22.07 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Baseline | 39.3 millimeters (mm) | Standard Deviation 28.43 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 40 | 22 millimeters (mm) | Standard Deviation 15.81 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 28 | 0 millimeters (mm) | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 104 | 17.8 millimeters (mm) | Standard Deviation 13.02 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 24 | 8.5 millimeters (mm) | Standard Deviation 9.33 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 12 | 27.5 millimeters (mm) | Standard Deviation 26.51 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 4 | 32.0 millimeters (mm) | Standard Deviation 24.54 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 104 | 25.7 millimeters (mm) | Standard Deviation 24.7 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Baseline | 51.0 millimeters (mm) | Standard Deviation 15.64 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 4 | 48.5 millimeters (mm) | Standard Deviation 30.71 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 12 | 33 millimeters (mm) | Standard Deviation 26.72 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 24 | 20.3 millimeters (mm) | Standard Deviation 28.51 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 28 | 0 millimeters (mm) | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) | Week 40 | 25.7 millimeters (mm) | Standard Deviation 31.56 |
Secondary
Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life (QOL), pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor.
Time frame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Population: Pharmacodynamic analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28-ADL | 52.9 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24-ADL | 55.9 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12-ADL | 72.1 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72-ADL | 48.5 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4-ADL | 79.4 Score on a scale | Standard Deviation 20.8 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40- ADL | 79.4 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline-ADL | 65.4 Score on a scale | Standard Deviation 3.12 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72-ADL | 88.2 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4-ADL | 91.2 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104- ADL | 77.9 Score on a scale | — |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12-ADL | 97.1 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24-ADL | 0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline-ADL | 69.1 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28-ADL | 83.8 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40- ADL | 95.6 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72-ADL | 78.7 Score on a scale | Standard Deviation 20.82 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40- ADL | 73.5 Score on a scale | Standard Deviation 29.12 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline-ADL | 77.3 Score on a scale | Standard Deviation 7.87 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 48-ADL | 85.3 Score on a scale | Standard Deviation 13.5 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12-ADL | 87.4 Score on a scale | Standard Deviation 15.1 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4-ADL | 86.5 Score on a scale | Standard Deviation 10.37 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24-ADL | 89.6 Score on a scale | Standard Deviation 10.75 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28-ADL | 0 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104- ADL | 93.5 Score on a scale | Standard Deviation 7.74 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline-ADL | 70.6 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24-ADL | 79.4 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72-ADL | 91.2 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104- ADL | 97.1 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40- ADL | 89.7 Score on a scale | — |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12-ADL | 94.1 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4-ADL | 89.7 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104- ADL | 87.5 Score on a scale | Standard Deviation 17.68 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline-ADL | 71.3 Score on a scale | Standard Deviation 30.16 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4-ADL | 76.0 Score on a scale | Standard Deviation 18.97 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12-ADL | 76.5 Score on a scale | Standard Deviation 23.53 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24-ADL | 73.0 Score on a scale | Standard Deviation 28.83 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40- ADL | 89.0 Score on a scale | Standard Deviation 15.6 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72-ADL | 100 Score on a scale | Standard Deviation 0 |
Secondary
Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life, pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor.
Time frame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Population: Pharmacodynamic analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline-Knee | 15.6 Score on a scale | Standard Deviation 13.26 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4-Knee | 31.3 Score on a scale | Standard Deviation 17.68 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12-Knee | 37.5 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24-Knee | 43.8 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28-Knee | 12.5 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40- Knee | 37.5 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72-Knee | 25.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28-Knee | 56.3 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104- Knee | 50.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline-Knee | 37.5 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72-Knee | 56.3 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12-Knee | 56.3 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4-Knee | 56.3 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40- Knee | 62.5 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4-Knee | 43.8 Score on a scale | Standard Deviation 22.88 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12-Knee | 54.4 Score on a scale | Standard Deviation 28.72 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24-Knee | 50.7 Score on a scale | Standard Deviation 34.3 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104- Knee | 59.8 Score on a scale | Standard Deviation 21.61 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28-Knee | 46.9 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40- Knee | 37.5 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 48-Knee | 48.4 Score on a scale | Standard Deviation 25.61 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72-Knee | 45.0 Score on a scale | Standard Deviation 26.81 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline-Knee | 29.5 Score on a scale | Standard Deviation 23.23 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40- Knee | 50.0 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72-Knee | 68.8 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24-Knee | 43.8 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104- Knee | 68.8 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12-Knee | 62.5 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline-Knee | 50.0 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4-Knee | 43.8 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28-Knee | 68.8 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72-Knee | 68.8 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40- Knee | 68.8 Score on a scale | Standard Deviation 8.84 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline-Knee | 40.6 Score on a scale | Standard Deviation 4.42 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104- Knee | 62.5 Score on a scale | Standard Deviation 17.68 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28-Knee | 56.3 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24-Knee | 41.7 Score on a scale | Standard Deviation 21.95 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4-Knee | 45.8 Score on a scale | Standard Deviation 13.01 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12-Knee | 43.8 Score on a scale | Standard Deviation 16.54 |
Secondary
Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life, pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor.
Time frame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Population: Pharmacodynamic analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 54.2 Score on a scale | Standard Deviation 5.89 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 58.3 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 66.7 Score on a scale | Standard Deviation 19.64 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 55.6 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24 | 52.8 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 55.6 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 47.2 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 75.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 52.8 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104 | 58.3 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 80.6 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 69.4 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 77.8 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 66.7 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 62.6 Score on a scale | Standard Deviation 17.5 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 62.2 Score on a scale | Standard Deviation 25.43 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104 | 77.7 Score on a scale | Standard Deviation 13.12 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 73.5 Score on a scale | Standard Deviation 18.19 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24 | 77.5 Score on a scale | Standard Deviation 21.22 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 48 | 71.5 Score on a scale | Standard Deviation 21.45 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 70.8 Score on a scale | Standard Deviation 41.25 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 56.9 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 75.6 Score on a scale | Standard Deviation 20.32 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24 | 61.1 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 66.7 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 75.0 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 75.0 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 83.3 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 80.6 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 88.9 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104 | 91.7 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24 | 69.4 Score on a scale | Standard Deviation 25.46 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 71.3 Score on a scale | Standard Deviation 15.8 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104 | 72.2 Score on a scale | Standard Deviation 27.5 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 91.7 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 63.0 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 61.1 Score on a scale | Standard Deviation 23.57 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 79.2 Score on a scale | Standard Deviation 21.61 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 88.9 Score on a scale | Standard Deviation 0 |
Secondary
Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life, pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor.
Time frame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Population: Pharmacodynamic analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 35.0 Score on a scale | Standard Deviation 7.07 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 50.0 Score on a scale | Standard Deviation 21.21 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 45.0 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24 | 30.0 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 35.0 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 35.0 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 30.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 35.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104 | 30.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 25.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 40.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 85.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 70.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 50.0 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 40.9 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 58.0 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24 | 55.6 Score on a scale | Standard Deviation 30.66 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104 | 58.2 Score on a scale | Standard Deviation 21.54 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 50.0 Score on a scale | Standard Deviation 70.71 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 37.5 Score on a scale | Standard Deviation 53.03 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 48 | 48.1 Score on a scale | Standard Deviation 39.27 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 40.6 Score on a scale | Standard Deviation 36.27 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 29.5 Score on a scale | Standard Deviation 23.15 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 90.0 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 70.0 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24 | 50.0 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104 | 95.0 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 85.0 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 70.0 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 100.0 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 95.0 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 95.0 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 80.0 Score on a scale | Standard Deviation 21.21 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 52.5 Score on a scale | Standard Deviation 31.82 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104 | 70.0 Score on a scale | Standard Deviation 35.36 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 95.0 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24 | 53.3 Score on a scale | Standard Deviation 37.53 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 48.3 Score on a scale | Standard Deviation 45.37 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 45.0 Score on a scale | Standard Deviation 37.75 |
Secondary
Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life, pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor.
Time frame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Population: Pharmacodynamic analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 41.1 Score on a scale | Standard Deviation 12.63 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 58.9 Score on a scale | Standard Deviation 32.83 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 71.4 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24 | 50.0 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 60.7 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 75.0 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 50.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 60.7 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104 | 53.6 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 50.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 57.1 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 78.6 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 75.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 64.3 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 59.4 Score on a scale | Standard Deviation 16.92 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 69.3 Score on a scale | Standard Deviation 21.31 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24 | 65.9 Score on a scale | Standard Deviation 25.45 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104 | 67.3 Score on a scale | Standard Deviation 20.63 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 62.5 Score on a scale | Standard Deviation 53.03 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 42.9 Score on a scale | Standard Deviation 60.61 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 48 | 62.1 Score on a scale | Standard Deviation 24.29 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 40.6 Score on a scale | Standard Deviation 28.43 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 50.0 Score on a scale | Standard Deviation 16.44 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 78.6 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 78.6 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24 | 67.9 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104 | 85.7 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 64.3 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 50.0 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 57.1 Score on a scale | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 75.0 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 72 | 85.7 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 40 | 73.2 Score on a scale | Standard Deviation 37.88 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Baseline | 62.5 Score on a scale | Standard Deviation 27.78 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 104 | 62.5 Score on a scale | Standard Deviation 32.83 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 28 | 89.3 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 24 | 67.9 Score on a scale | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 4 | 57.1 Score on a scale | Standard Deviation 24.74 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) | Week 12 | 56.0 Score on a scale | Standard Deviation 26.33 |
Secondary
Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire
The EQ-5D is a standardized measure of health status. The EQ visual analogue scale (EQ VAS)has a range from 0-100: worst possible to perfect health. Data show the absolute change from baseline of EQ5D VAS and at the different visits for participants, who received multiple doses of MCS110. (PART B and PART C).
Time frame: Week 4, Week 24, up to 104 weeks
Population: Pharmacodynamic analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Week 24 | -1.0 Score on a scale | Standard Deviation 0 |
| Placebo (PART ABC4) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Week 4 | 11.0 Score on a scale | Standard Deviation 1.41 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Week 24 | 10.0 Score on a scale | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Week 4 | 3.7 Score on a scale | Standard Deviation 5.03 |
| MCS110 3 mg/kg (PART ABC4) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Up to Week 104 | 1.3 Score on a scale | Standard Deviation 5.51 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Week 24 | 9.5 Score on a scale | Standard Deviation 14.04 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Week 4 | 0.6 Score on a scale | Standard Deviation 25.07 |
| MCS110 5 mg/kg (PART ABC4) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Up to Week 104 | 6.9 Score on a scale | Standard Deviation 13.93 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Week 24 | 1.0 Score on a scale | Standard Deviation 8.54 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Week 4 | 1.3 Score on a scale | Standard Deviation 2.5 |
| MCS110 10 mg/kg (PART ABC4) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Up to Week 104 | 7.0 Score on a scale | Standard Deviation 8.91 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Week 24 | 9.8 Score on a scale | Standard Deviation 16.21 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Up to Week 104 | 18.0 Score on a scale | Standard Deviation 25.63 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire | Week 4 | 5.5 Score on a scale | Standard Deviation 10.85 |
Secondary
Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time
Pharmacokinetic characterization of a single dose of MCS110 for evaluation of macrophage-colony stimulating factor (M-CSF) plasma concentrations over time
Time frame: Baseline, Day 1, Day 85, Day 169
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Baseline | 4694.0 pg/mL | Standard Deviation 1375.4 |
| Placebo (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 85 | 1697500.0 pg/mL | Standard Deviation 646445.41 |
| Placebo (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 1 | 4762.5 pg/mL | Standard Deviation 2256.34 |
| Placebo (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 169 | 173750.0 pg/mL | Standard Deviation 103345.3 |
| MCS110 3 mg/kg (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 1 | 5060.0 pg/mL | Standard Deviation 0 |
| MCS110 3 mg/kg (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 169 | 469.0 pg/mL | Standard Deviation 1357.65 |
| MCS110 3 mg/kg (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Baseline | 4940.0 pg/mL | Standard Deviation 650.54 |
| MCS110 3 mg/kg (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 85 | 4235.0 pg/mL | Standard Deviation 544.47 |
| MCS110 5 mg/kg (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Baseline | 5767.1 pg/mL | Standard Deviation 1159.12 |
| MCS110 5 mg/kg (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 85 | 4238571.4 pg/mL | Standard Deviation 1446575.6 |
| MCS110 5 mg/kg (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 169 | 5668750.0 pg/mL | Standard Deviation 1928829.68 |
| MCS110 5 mg/kg (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 1 | 6405.0 pg/mL | Standard Deviation 4103.8 |
| MCS110 10 mg/kg (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 85 | 4526666.7 pg/mL | Standard Deviation 1127578.53 |
| MCS110 10 mg/kg (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 1 | 4916.7 pg/mL | Standard Deviation 545.19 |
| MCS110 10 mg/kg (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 169 | 5360000.0 pg/mL | Standard Deviation 1173797.26 |
| MCS110 10 mg/kg (PART ABC4) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Baseline | 5056.7 pg/mL | Standard Deviation 1769.67 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 169 | 2290000.0 pg/mL | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Baseline | 4778.3 pg/mL | Standard Deviation 2078.12 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 1 | 4688.3 pg/mL | Standard Deviation 1506.46 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 85 | 4750000.0 pg/mL | Standard Deviation 0 |
| MCS110 5 mg/kg (PART C) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 1 | 5281.4 pg/mL | Standard Deviation 2687.57 |
| MCS110 5 mg/kg (PART C) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Baseline | 5420.0 pg/mL | Standard Deviation 3126.2 |
| MCS110 5 mg/kg (PART C) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 85 | 4060000.0 pg/mL | Standard Deviation 0 |
| MCS110 5 mg/kg (PART C) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 169 | 4090000.0 pg/mL | Standard Deviation 0 |
| MCS110 10 mg/kg (PART C) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 1 | 4423.3 pg/mL | Standard Deviation 1134.43 |
| MCS110 10 mg/kg (PART C) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Baseline | 3360.0 pg/mL | Standard Deviation 747.46 |
| MCS110 10 mg/kg (PART C) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 169 | 5480000.0 pg/mL | Standard Deviation 1225724.28 |
| MCS110 10 mg/kg (PART C) | Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time | Day 85 | 4580000.0 pg/mL | Standard Deviation 575065.21 |
Secondary
Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I).
Pharmacodynamic characterization of a single dose of MCS110 by measuring C-terminal telopeptide of Type 1 Collagen peptide (CTX-I), a biomarker of bone resorption. Data measured in participants from three arms: participants from Part A, B and C who received a single dose of 10 mg/kg and had assessment at week 4 (Part ABC4); participants from Part A and B who received placebo ; and participants from Part B and C who received multiple monthly doses of MCS110 (10 mg/kg.) Serum CTX-I data were generated in Part A and Part B. In Part C, samples were collected for serum bone CTX-I analysis. The analysis was not performed, as enough information on compound mode of action was obtained using creatine kinase (CK) and monocytes (hematology) data. Only data from 10mg/kg (single and multiple doses) are available.
Time frame: Baseline, Week 4, Week 24, Week 104
Population: Pharmacodynamic analysis
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo (PART ABC4) | Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I). | Week 4 | 0.1 ng/mL |
| Placebo (PART ABC4) | Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I). | Baseline | 0.3 ng/mL |
| MCS110 3 mg/kg (PART ABC4) | Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I). | Week 4 | 0.6 ng/mL |
| MCS110 3 mg/kg (PART ABC4) | Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I). | Baseline | 0.5 ng/mL |
| MCS110 5 mg/kg (PART ABC4) | Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I). | Week 24 | 0.1 ng/mL |
| MCS110 5 mg/kg (PART ABC4) | Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I). | Baseline | 0.4 ng/mL |
| MCS110 5 mg/kg (PART ABC4) | Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I). | Week 4 | 0.1 ng/mL |
| MCS110 5 mg/kg (PART ABC4) | Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I). | Week 104 | 0.3 ng/mL |
Secondary
Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes
Blood samples were collected for the evaluation of CD14+ monocytes (using FACS) and CD14+ CD16+ monocytes. Based on preliminary analysis, the quality of the samples did not allow meaningful conclusions to be drawn. Thus, in Part B, the monocyte sample collection was discontinued.
Time frame: Baseline Up to Week 104
Population: Pharmacodynamic analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PART ABC4) | Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes | NA Number of Monocytes |
| MCS110 3 mg/kg (PART ABC4) | Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes | NA Number of Monocytes |
| MCS110 5 mg/kg (PART ABC4) | Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes | NA Number of Monocytes |
| MCS110 10 mg/kg (PART ABC4) | Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes | NA Number of Monocytes |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes | NA Number of Monocytes |
| MCS110 5 mg/kg (PART C) | Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes | NA Number of Monocytes |
| MCS110 10 mg/kg (PART C) | Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes | NA Number of Monocytes |
Secondary
Number of Participants With Negative Anti-MCS110 Antibody
To assess the immunogenicity of MCS110 in serum anti-MCS110 antibody concentrations
Time frame: Baseline, throughout the study up to Day 505
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 29 | 4 Number of Participants |
| Placebo (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 169 | 4 Number of Participants |
| Placebo (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 85 | 3 Number of Participants |
| Placebo (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Baseline | 5 Number of Participants |
| Placebo (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 127 | 3 Number of Participants |
| MCS110 3 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 169 | 2 Number of Participants |
| MCS110 3 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 85 | 2 Number of Participants |
| MCS110 3 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Baseline | 1 Number of Participants |
| MCS110 3 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 29 | 2 Number of Participants |
| MCS110 3 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 127 | 1 Number of Participants |
| MCS110 5 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Baseline | 8 Number of Participants |
| MCS110 5 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 85 | 7 Number of Participants |
| MCS110 5 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 336 | 7 Number of Participants |
| MCS110 5 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 169 | 7 Number of Participants |
| MCS110 5 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 29 | 8 Number of Participants |
| MCS110 5 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 505 | 6 Number of Participants |
| MCS110 10 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 29 | 3 Number of Participants |
| MCS110 10 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Baseline | 3 Number of Participants |
| MCS110 10 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 85 | 3 Number of Participants |
| MCS110 10 mg/kg (PART ABC4) | Number of Participants With Negative Anti-MCS110 Antibody | Day 169 | 1 Number of Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 85 | 1 Number of Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Negative Anti-MCS110 Antibody | Baseline | 3 Number of Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 393 | 1 Number of Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 29 | 2 Number of Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 169 | 1 Number of Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 505 | 1 Number of Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 85 | 3 Number of Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 393 | 2 Number of Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Baseline | 3 Number of Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 169 | 3 Number of Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 505 | 4 Number of Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 29 | 4 Number of Participants |
| MCS110 5 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 336 | 2 Number of Participants |
| MCS110 10 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 169 | 3 Number of Participants |
| MCS110 10 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 85 | 3 Number of Participants |
| MCS110 10 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 29 | 4 Number of Participants |
| MCS110 10 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Baseline | 3 Number of Participants |
| MCS110 10 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 393 | 4 Number of Participants |
| MCS110 10 mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 505 | 4 Number of Participants |
| MCS110 3 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 169 | 3 Number of Participants |
| MCS110 3 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 393 | 4 Number of Participants |
| MCS110 3 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 85 | 3 Number of Participants |
| MCS110 3 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 29 | 4 Number of Participants |
| MCS110 3 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 505 | 3 Number of Participants |
| MCS110 3 mg/kg & MCS110 10mg/kg (Part C) | Number of Participants With Negative Anti-MCS110 Antibody | Baseline | 4 Number of Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 29 | 3 Number of Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 169 | 4 Number of Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 505 | 2 Number of Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Baseline | 4 Number of Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 85 | 4 Number of Participants |
| MCS110 5 mg/kg & MCS110 10mg/kg (PART C) | Number of Participants With Negative Anti-MCS110 Antibody | Day 393 | 2 Number of Participants |
Secondary
Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC)
Pharmacokinetic for a single dose of MCS110 for serum concentration -time curve (AUC).
Time frame: Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr)
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC) | Day 1 | 75632187 h* ng/mL | Standard Deviation 16664282 |
| MCS110 3 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC) | Day 85 | 256238447 h* ng/mL | Standard Deviation 140220044 |
| MCS110 3 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC) | Day 1 | 44258092 h* ng/mL | Standard Deviation 6489002 |
| MCS110 5 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC) | Day 112 | 238619590 h* ng/mL | Standard Deviation 63815086 |
| MCS110 5 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC) | Day 29 | 838099 h* ng/mL | Standard Deviation 171148 |
| MCS110 10 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC) | Day 1 | 12900096 h* ng/mL | Standard Deviation 2373049 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC) | Day 1 | 14559871 h* ng/mL | Standard Deviation 7783073 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC) | Day 85 | 179084.13 h* ng/mL | Standard Deviation 0 |
| MCS110 5 mg/kg (PART C) | Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC) | Day 85 | 999719 h* ng/mL | Standard Deviation 278619 |
| MCS110 5 mg/kg (PART C) | Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC) | Day 1 | 44854588 h* ng/mL | Standard Deviation 9743190 |
Secondary
Pharmacokinetics of MCS110 Maximum Concentration (Cmax)
Pharmacokinetic characterization of a single dose of MCS110 for maximum serum concentration (Cmax)
Time frame: Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr)
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PART ABC4) | Pharmacokinetics of MCS110 Maximum Concentration (Cmax) | Day 1 | 234800 ng/mL | Standard Deviation 40598 |
| MCS110 3 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Maximum Concentration (Cmax) | Day 85 | 309429 ng/mL | Standard Deviation 54464 |
| MCS110 3 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Maximum Concentration (Cmax) | Day 1 | 206750 ng/mL | Standard Deviation 32745 |
| MCS110 5 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Maximum Concentration (Cmax) | Day 112 | 239000 ng/mL | Standard Deviation 55154 |
| MCS110 5 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Maximum Concentration (Cmax) | Day 29 | 194667 ng/mL | Standard Deviation 36828 |
| MCS110 10 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Maximum Concentration (Cmax) | Day 1 | 66983 ng/mL | Standard Deviation 8493 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Pharmacokinetics of MCS110 Maximum Concentration (Cmax) | Day 1 | 85914 ng/mL | Standard Deviation 15539 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Pharmacokinetics of MCS110 Maximum Concentration (Cmax) | Day 85 | 97750 ng/mL | Standard Deviation 11667 |
| MCS110 5 mg/kg (PART C) | Pharmacokinetics of MCS110 Maximum Concentration (Cmax) | Day 85 | 255000 ng/mL | Standard Deviation 30199 |
| MCS110 5 mg/kg (PART C) | Pharmacokinetics of MCS110 Maximum Concentration (Cmax) | Day 1 | 214667 ng/mL | Standard Deviation 39119 |
Secondary
Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax)
Pharmacokinetic characterization of a single dose of MCS110 for time to maximum concentration (Tmax)
Time frame: Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr)
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo (PART ABC4) | Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax) | Day 1 | 2.083 hour (h) |
| MCS110 3 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax) | Day 85 | 1.25 hour (h) |
| MCS110 3 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax) | Day 1 | 1.192 hour (h) |
| MCS110 5 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax) | Day 112 | 3.1 hour (h) |
| MCS110 5 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax) | Day 29 | 1.467 hour (h) |
| MCS110 10 mg/kg (PART ABC4) | Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax) | Day 1 | 3.125 hour (h) |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax) | Day 1 | 5 hour (h) |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax) | Day 85 | 3.533 hour (h) |
| MCS110 5 mg/kg (PART C) | Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax) | Day 85 | 1.233 hour (h) |
| MCS110 5 mg/kg (PART C) | Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax) | Day 1 | 4 hour (h) |
Secondary
Time to Relapse
Time to relapse describes the time frame from baseline when the tumor volume increases again after the treatment with MCS110. To be considered a relapse tumor volume had to increase greater than 50% of the difference between tumor volume at baseline and the lowest tumor volume measured by MRI. In this assessment the Part B and Part C patients were analyzed separately. N/A (not available):Data analysis not performed as sample size was not analyzable as no patient had surgery/relapse.
Time frame: Up to Week 104
Population: Pharmacodynamic analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PART ABC4) | Time to Relapse | 337.0 Days | Standard Deviation 108.89 |
| MCS110 3 mg/kg (PART ABC4) | Time to Relapse | 454.0 Days | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Time to Relapse | 477.0 Days | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Time to Relapse | 296.0 Days | Standard Deviation 103.24 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Time to Relapse | NA Days | — |
| MCS110 5 mg/kg (PART C) | Time to Relapse | NA Days | — |
Secondary
Time to Surgery
Time to surgery describes the time frame from baseline to the time point when participants had surgical removement of PVNS tumor. This could be either residual tumor after the tumor volume was reduced or surgery due to relapse. In this assessment the Part B and Part C patients were analyzed separately. Not Available (NA): Data analysis not performed as sample size was not analyzable as no patient had surgery.
Time frame: Up to Week 104
Population: Pharmacodynamic analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PART ABC4) | Time to Surgery | 387.0 Days | Standard Deviation 116.25 |
| MCS110 3 mg/kg (PART ABC4) | Time to Surgery | 0 Days | Standard Deviation 0 |
| MCS110 5 mg/kg (PART ABC4) | Time to Surgery | 0 Days | Standard Deviation 0 |
| MCS110 10 mg/kg (PART ABC4) | Time to Surgery | 231.0 Days | Standard Deviation 0 |
| MCS110 5 mg/kg & MCS110 10mg/kg (Part C) | Time to Surgery | NA Days | — |
| MCS110 5 mg/kg (PART C) | Time to Surgery | NA Days | — |