A Phase 2 interventional study of MCS110 and Placebo in Pigmented Villonodular Synovitis, PVNS and Giant Cell Tumor of the Tendon Sheath, sponsored by Novartis Pharmaceuticals. Completed at 8 sites in 2 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2021-01-05.
Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment
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.
Exclusion criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
Participants will receive a single dose of 10mg/kg on day 1 administered by regular infusion.
Drug: MCS110
Part A: single-dose placebo to match MCS110 (10 mg/kg, 1 h i.v. infusion) Part B: single dose placebo to match MCS110 (10 mg/kg, 1 h i.v. infusion administered i.v. at Day 1, followed by 6 doses of placebo to match MCS110 (10 mg/kg)
Drug: Placebo
Part C: MCS110 3 mg/kg (i.v. infusion)
Drug: MCS110
Part C: MCS110 5 mg/kg (i.v. infusion)
Drug: MCS110
Part C: MCS110 10 mg/kg (i.v. infusion)
Drug: MCS110
Part C: MCS110 3 mg/kg (i.v. infusion) \& MCS110 10 mg/kg (i.v. infusion)
Drug: MCS110
Part C: MCS110 5 mg/kg (i.v. infusion) \& MCS110 10 mg/kg (i.v. infusion)
Drug: MCS110
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.
Also known as: Intravenous infusion of MCS110.
Participants will receive a single dose of NaCl on day 1 through intravenous infusion.
Also known as: Intravenous infusion of placebo.
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
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
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
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
Number of Participants With Adverse Events
Overall incidence of Adverse Events
Time frame: Approximately 2 years
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)
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)
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)
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
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
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
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
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
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
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
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
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
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
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)
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)
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)
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)
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)
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
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.
| Milestone | 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) |
|---|---|---|---|---|---|---|---|---|---|
| Started | 5 | 2 | 8 | 3 | 3 | 3 | 4 | 4 | 4 |
| Completed | 5 | 2 | 7 | 3 | 0 | 3 | 3 | 4 | 3 |
| Not completed | 0 | 0 | 1 | 0 | 3 | 0 | 1 | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Administrative problems | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
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".
| mm3 | Placebo (PART ABC4) | MCS110 3 mg/kg (PART ABC4) | MCS110 5 mg/kg (PART ABC4) | MCS110 10 mg/kg (PART ABC4) |
|---|---|---|---|---|
| Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size | -4222.8 ± 6284.56 | -668.5 ± 18751.44 | -9998.4 ± 15628.40 | -38002.1 ± 57314.73 |
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".
| Percentage | Placebo (PART ABC4) | MCS110 3 mg/kg (PART ABC4) | MCS110 5 mg/kg (PART ABC4) | MCS110 10 mg/kg (PART ABC4) |
|---|---|---|---|---|
| Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size | -7.7 ± 5.10 | -7.4 ± 13.21 | -24.8 ± 23.42 | -32.6 ± 16.61 |
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 \[5/10 mg/kg\]
| mm3 | MCS110 3 mg/kg (PART C) | MCS110 5 mg/kg (PART C) | MCS110 10 mg/kg (PART BC) | MCS110 3 mg/kg & MCS110 10mg/kg (Part C) | 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 | -2450.3 ± 2721.24 | -29164.3 ± 23286.18 | -37015.1 ± 29297.02 | -42420.1 ± 63812.69 | -3571.9 ± 3612.97 |
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 \[5/10 mg/kg\].
| Percentage | MCS110 3 mg/kg (PART BC) | MCS110 5 mg/kg (PART BC) | MCS110 10 mg/kg (PART BC) | MCS110 3 mg/kg & MCS110 10mg/kg (Part BC) | MCS110 5 mg/kg & MCS110 10mg/kg (Part BC) |
|---|---|---|---|---|---|
| Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size | -29.7 ± 33.73 | -56.3 ± 20.31 | -55.0 ± 19.02 | -45.8 ± 40.11 | -22.6 ± 16.21 |
Overall incidence of Adverse Events
| Participants | MCS110 10 mg/kg (PART A) | Placebo (PART A) | MCS110 10 mg/kg (PART B) | Placebo (PART B) | MCS110 3 mg/kg (PART C) | MCS110 5 mg/kg (PART C) | MCS110 10 mg/kg (PART C) |
|---|---|---|---|---|---|---|---|
| AEs of mild severity | 3 | 1 | 11 | 1 | 7 | 6 | 11 |
| AEs of moderate severity | 1 | 1 | 9 | 2 | 4 | 2 | 5 |
| AEs of severe severity | 0 | 0 | 4 | 0 | 2 | 1 | 4 |
| Study drug related AEs | 3 | 1 | 10 | 1 | 7 | 5 | 8 |
| Serious AEs | 0 | 1 | 2 | 0 | 3 | 1 | 4 |
| AEs leading to discontinuation | 0 | 0 | 0 | 0 | 2 | 1 | 1 |
Pharmacokinetic for a single dose of MCS110 for serum concentration -time curve (AUC).
| h* ng/mL | MCS110 10 mg/kg (PART A) | MCS110 10 mg/kg (PART B) | Placebo/10 mg kg (PART B) | MCS110 3 mg/kg (PART C) | MCS110 5 mg/kg (PART C) | MCS110 mg/kg (PART C) |
|---|---|---|---|---|---|---|
| Day 1 | 75632187 ± 16664282 | 44258092 ± 6489002 | — | 12900096 ± 2373049 | 14559871 ± 7783073 | 44854588 ± 9743190 |
| Day 29 | — | — | 838099 ± 171148 | — | — | — |
| Day 85 | — | 256238447 ± 140220044 | — | — | 179084.13 ± 0 | 999719 ± 278619 |
| Day 112 | — | — | 238619590 ± 63815086 | — | — | — |
Pharmacokinetic characterization of a single dose of MCS110 for maximum serum concentration (Cmax)
| ng/mL | MCS110 10 mg/kg (PART A) | MCS110 10 mg/kg (PART B) | Placebo/10 mg kg (PART B) | MCS110 3 mg/kg (PART C) | MCS110 5 mg/kg (PART C) | MCS110 mg/kg (PART C) |
|---|---|---|---|---|---|---|
| Day 1 | 234800 ± 40598 | 206750 ± 32745 | — | 66983 ± 8493 | 85914 ± 15539 | 214667 ± 39119 |
| Day 29 | — | — | 194667 ± 36828 | — | — | — |
| Day 85 | — | 309429 ± 54464 | — | — | 97750 ± 11667 | 255000 ± 30199 |
| Day 112 | — | — | 239000 ± 55154 | — | — | — |
Pharmacokinetic characterization of a single dose of MCS110 for time to maximum concentration (Tmax)
| hour (h) | MCS110 10 mg/kg (PART A) | MCS110 10 mg/kg (PART B) | Placebo/10 mg kg (PART B) | MCS110 3 mg/kg (PART C) | MCS110 5 mg/kg (PART C) | MCS110 mg/kg (PART C) |
|---|---|---|---|---|---|---|
| Day 1 | 2.083 (1.083 to 3.083) | 1.192 (1 to 5.05) | — | 3.125 (1.083 to 5.083) | 5 (0 to 5.033) | 4 (1.083 to 5.067) |
| Day 29 | — | — | 1.467 (1 to 1.5) | — | — | — |
| Day 85 | — | 1.25 (1 to 5) | — | — | 3.533 (2.033 to 5.033) | 1.233 (1.083 to 5.05) |
| Day 112 | — | — | 3.1 (1.017 to 5.183) | — | — | — |
Pharmacokinetic characterization of a single dose of MCS110 for evaluation of macrophage-colony stimulating factor (M-CSF) plasma concentrations over time
| pg/mL | MCS110 10 mg/kg (PART A) | Placebo/MCS110 10mg/kg (PART A) | MCS110 10 mg/kg (PART B) | Placebo/10 mg kg (PART B) | MCS110 3 mg/kg (PART C) | MCS110 5 mg/kg (PART C) | MCS110 mg/kg (PART C) |
|---|---|---|---|---|---|---|---|
| Baseline | 4694.0 ± 1375.40 | 4940.0 ± 650.54 | 5767.1 ± 1159.12 | 5056.7 ± 1769.67 | 4778.3 ± 2078.12 | 5420.0 ± 3126.20 | 3360.0 ± 747.46 |
| Day 1 | 4762.5 ± 2256.34 | 5060.0 ± 0 | 6405.0 ± 4103.80 | 4916.7 ± 545.19 | 4688.3 ± 1506.46 | 5281.4 ± 2687.57 | 4423.3 ± 1134.43 |
| Day 85 | 1697500.0 ± 646445.41 | 4235.0 ± 544.47 | 4238571.4 ± 1446575.60 | 4526666.7 ± 1127578.53 | 4750000.0 ± 0 | 4060000.0 ± 0 | 4580000.0 ± 575065.21 |
| Day 169 | 173750.0 ± 103345.30 | 469.0 ± 1357.65 | 5668750.0 ± 1928829.68 | 5360000.0 ± 1173797.26 | 2290000.0 ± 0 | 4090000.0 ± 0 | 5480000.0 ± 1225724.28 |
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.
| ng/mL | MCS110 10 mg/kg (PART ABC4) | Placebo (PARTS A and B) | MCS110 10 mg/kg (PART BC) |
|---|---|---|---|
| Baseline | 0.3 (0.2 to 0.5) | 0.5 (0.4 to 1.0) | 0.4 (0.2 to 0.6) |
| Week 4 | 0.1 (0.0 to 0.1) | 0.6 (0.2 to 0.8) | 0.1 (0.0 to 0.2) |
| Week 24 | — | — | 0.1 (0.0 to 0.2) |
| Week 104 | — | — | 0.3 (0.2 to 0.8) |
To assess the immunogenicity of MCS110 in serum anti-MCS110 antibody concentrations
| Number of Participants | MCS110 10 mg/kg (PART A) | Placebo (PART A) | MCS110 10 mg/kg (PART B) | Placebo (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) |
|---|---|---|---|---|---|---|---|---|---|
| Baseline | 5 | 1 | 8 | 3 | 3 | 3 | 3 | 4 | 4 |
| Day 29 | 4 | 2 | 8 | 3 | 2 | 4 | 4 | 4 | 3 |
| Day 85 | 3 | 2 | 7 | 3 | 1 | 3 | 3 | 3 | 4 |
| Day 127 | 3 | 1 | — | — | — | — | — | — | — |
| Day 169 | 4 | 2 | 7 | 1 | 1 | 3 | 3 | 3 | 4 |
| Day 336 | — | — | 7 | — | — | 2 | — | — | — |
| Day 393 | — | — | — | — | 1 | 2 | 4 | 4 | 2 |
| Day 505 | — | — | 6 | — | 1 | 4 | 4 | 3 | 2 |
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".
| Degree | Placebo (PART ABC4) | MCS110 3 mg/kg (PART ABC4) | MCS110 5 mg/kg (PART ABC4) | MCS110 10 mg/kg (PART ABC4) |
|---|---|---|---|---|
| Knee Extension | -7.3 ± 4.99 | -12.3 ± 13.65 | 1.7 ± 2.89 | -10.3 ± 26.69 |
| Knee Flexion | -2.8 ± 8.85 | 3.7 ± 13.5 | 13.7 ± 19.76 | -15.4 ± 43.13 |
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 \[5/10 mg/kg\].
| Degree | MCS110 3 mg/kg (Part BC) | MCS110 5 mg/kg (Part BC) | MCS110 10 mg/kg (Part BC) | MCS110 3 mg/kg & MCS110 10mg/kg (PART BC) | MCS110 5 mg/kg & MCS110 10mg/kg (PART BC) |
|---|---|---|---|---|---|
| Week 24/28: Knee extension | -10.0 ± 0.00 | 0.0 ± 0.0 | -10.5 ± 21.36 | -26 ± 0.0 | 1 ± 1.73 |
| Week 24/28:(Knee Flexion) | -2.0 ± 0.00 | 8 ± 0.00 | 9.9 ± 8.77 | 8 ± 0.0 | 53.0 ± 61.54 |
| Week 104:(Knee Extension) | — | 0 ± 0 | -3.5 ± 6.07 | -28.0 ± 0.00 | 2.5 ± 3.54 |
| Week 104: (Knee Flexion) | — | -6 ± 0 | 7.5 ± 11.56 | 10 ± 0.00 | 70.0 ± 70.71 |
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 \[5/10 mg/kg\].
| millimeters (mm) | MCS110 3 mg/kg (PART BC) | MCS110 5 mg/kg (PART BC) | MCS110 10 mg/kg (PART BC) | MCS110 3 mg/kg & MCS110 10 mg/kg (PART BC) | MCS110 5 mg/kg & MCS110 10 mg/kg (PART BC) |
|---|---|---|---|---|---|
| Baseline | 32 ± 4.24 | 9.3 ± 12.74 | 28.6 ± 21.82 | 39.3 ± 28.43 | 51.0 ± 15.64 |
| Week 4 | 22.5 ± 20.51 | 4 ± 5.29 | 22.5 ± 23.87 | 32.0 ± 24.54 | 48.5 ± 30.71 |
| Week 12 | 20 ± 0 | 2.7 ± 3.06 | 13.9 ± 16.01 | 27.5 ± 26.51 | 33 ± 26.72 |
| Week 24 | 0 ± 0 | 0 ± 0 | 21.4 ± 22.07 | 8.5 ± 9.33 | 20.3 ± 28.51 |
| Week 28 | 40 ± 0 | 10.7 ± 17.62 | 0 ± 0 | 0 ± 0 | 0 ± 0 |
| Week 40 | 31 ± 0 | 3.7 ± 5.51 | 31.0 ± 31.38 | 22 ± 15.81 | 25.7 ± 31.56 |
| Week 48 | 0 ± 0 | 0 ± 0 | 21.0 ± 0 | — | — |
| Week 104 | 0 ± 0 | 16.0 ± 18.03 | 22.4 ± 24.23 | 17.8 ± 13.02 | 25.7 ± 24.7 |
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.
| Days | MCS110 10mg/kg (PART B) | MCS110 3 mg/kg (PART C) | MCS110 5 mg/kg (PART C) | MCS110 10 mg/kg (PART C) | MCS110 3/10 mg/kg (PART C) | MCS110 5/10 mg/kg (PART C) |
|---|---|---|---|---|---|---|
| Time to Relapse | 337.0 ± 108.89 | 454.0 ± 0 | 477.0 ± 0 | 296.0 ± 103.24 | NA ± NA | NA ± NA |
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.
| Days | MCS110 10mg/kg (PART B) | MCS110 3 mg/kg (PART C) | MCS110 5 mg/kg (PART C) | MCS110 10 mg/kg (PART C) | MCS110 3/10 mg/kg (PART C) | MCS110 5/10 mg/kg (PART C) |
|---|---|---|---|---|---|---|
| Time to Surgery | 387.0 ± 116.25 | 0 ± 0 | 0 ± 0 | 231.0 ± 0 | NA ± NA | NA ± NA |
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.
| Scores on a scale | MCS110 3 mg/kg (PART BC) | MCS110 5 mg/kg (PART BC) | MCS110 10 mg/kg (Part BC) | MCS110 3 mg/kg & MCS110 10mg/kg (PART BC) | MCS110 5 mg/kg & MCS110 10mg/kg (PART BC) |
|---|---|---|---|---|---|
| Baseline | 0.3 ± 0.35 | 0.1 ± 0.22 | 0.3 ± 0.20 | 0.3 ± 0.33 | 0.9 ± 0.52 |
| Week 104 | — | 0.1 ± 0.14 | 0.2 ± 0.18 | 0.1 ± 0.19 | 0.3 ± 0.25 |
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.
| Number of Monocytes | MCS110 10 mg/kg (PART A) | MCS110 10 mg/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) |
|---|---|---|---|---|---|---|---|
| Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes | NA | NA | NA | NA | NA | NA | NA |
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.
| Score on a scale | MCS110 3 mg/kg (PART BC) | MCS110 5 mg/kg (PART BC) | MCS110 10 mg/kg (Part BC) | MCS110 3 mg/kg & MCS110 10mg/kg (PART BC) | MCS110 5 mg/kg & MCS110 10mg/kg (PART BC) |
|---|---|---|---|---|---|
| Baseline-ADL | 65.4 ± 3.12 | 69.1 ± 0.00 | 77.3 ± 7.87 | 70.6 ± 0.00 | 71.3 ± 30.16 |
| Week 4-ADL | 79.4 ± 20.8 | 91.2 ± 0.00 | 86.5 ± 10.37 | 89.7 ± 0.00 | 76.0 ± 18.97 |
| Week 12-ADL | 72.1 ± 0.00 | 97.1 ± 0.00 | 87.4 ± 15.10 | 94.1 ± 0.00 | 76.5 ± 23.53 |
| Week 24-ADL | 55.9 ± 0.00 | 0 ± 0 | 89.6 ± 10.75 | 79.4 ± 0 | 73.0 ± 28.83 |
| Week 28-ADL | 52.9 ± 0 | 83.8 ± 0 | 0 ± 0 | — | — |
| Week 40- ADL | 79.4 ± 0 | 95.6 ± 0 | 73.5 ± 29.12 | 89.7 | 89.0 ± 15.6 |
| Week 48-ADL | — | — | 85.3 ± 13.50 | — | — |
| Week 72-ADL | 48.5 ± 0 | 88.2 ± 0 | 78.7 ± 20.82 | 91.2 ± 0 | 100 ± 0 |
| Week 104- ADL | — | 77.9 | 93.5 ± 7.74 | 97.1 ± 0 | 87.5 ± 17.68 |
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.
| Score on a scale | MCS110 3 mg/kg (PART BC) | MCS110 5 mg/kg (PART BC) | MCS110 10 mg/kg (Part BC) | MCS110 3 mg/kg & MCS110 10mg/kg (PART BC) | MCS110 5 mg/kg & MCS110 10mg/kg (PART BC) |
|---|---|---|---|---|---|
| Baseline-Knee | 15.6 ± 13.26 | 37.5 ± 0 | 29.5 ± 23.23 | 50.0 ± 0 | 40.6 ± 4.42 |
| Week 4-Knee | 31.3 ± 17.68 | 56.3 ± 0 | 43.8 ± 22.88 | 43.8 ± 0 | 45.8 ± 13.01 |
| Week 12-Knee | 37.5 ± 0 | 56.3 ± 0 | 54.4 ± 28.72 | 62.5 ± 0 | 43.8 ± 16.54 |
| Week 24-Knee | 43.8 ± 0 | — | 50.7 ± 34.30 | 43.8 ± 0 | 41.7 ± 21.95 |
| Week 28-Knee | 12.5 ± 0 | 56.3 ± 0 | 46.9 ± 0 | 68.8 ± 0 | 56.3 ± 0 |
| Week 40- Knee | 37.5 ± 0 | 62.5 ± 0 | 37.5 ± 0 | 50.0 ± 0 | 68.8 ± 8.84 |
| Week 48-Knee | — | — | 48.4 ± 25.61 | — | — |
| Week 72-Knee | 25.0 ± 0 | 56.3 ± 0 | 45.0 ± 26.81 | 68.8 ± 0 | 68.8 ± 0 |
| Week 104- Knee | — | 50.0 ± 0 | 59.8 ± 21.61 | 68.8 ± 0 | 62.5 ± 17.68 |
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.
| Score on a scale | MCS110 3 mg/kg (PART BC) | MCS110 5 mg/kg (PART BC) | MCS110 10 mg/kg (Part BC) | MCS110 3 mg/kg & MCS110 10mg/kg (PART BC) | MCS110 5 mg/kg & MCS110 10mg/kg (PART BC) |
|---|---|---|---|---|---|
| Baseline | 54.2 ± 5.89 | 52.8 ± 0 | 62.6 ± 17.50 | 66.7 ± 0 | 61.1 ± 23.57 |
| Week 4 | 66.7 ± 19.64 | 75.0 ± 0 | 73.5 ± 18.19 | 75.0 ± 0 | 63.0 ± 0 |
| Week 12 | 55.6 ± 0 | 80.6 ± 0 | 75.6 ± 20.32 | 75.0 ± 0 | 71.3 ± 15.80 |
| Week 24 | 52.8 ± 0 | — | 77.5 ± 21.22 | 61.1 ± 0 | 69.4 ± 25.46 |
| Week 28 | 55.6 ± 0 | 69.4 ± 0 | 70.8 ± 41.25 | 83.3 ± 0 | 88.9 ± 0 |
| Week 40 | 58.3 ± 0 | 77.8 ± 0 | 56.9 ± 0 | 80.6 ± 0 | 79.2 ± 21.61 |
| Week 48 | — | — | 71.5 ± 21.45 | — | — |
| Week 72 | 47.2 ± 0 | 66.7 ± 0 | 62.2 ± 25.43 | 88.9 ± 0 | 91.7 ± 0 |
| Week 104 | — | 58.3 ± 0 | 77.7 ± 13.12 | 91.7 ± 0 | 72.2 ± 27.50 |
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.
| Score on a scale | MCS110 3 mg/kg (PART BC) | MCS110 5 mg/kg (PART BC) | MCS110 10 mg/kg (Part BC) | MCS110 3 mg/kg & MCS110 10mg/kg (PART BC) | MCS110 5 mg/kg & MCS110 10mg/kg (PART BC) |
|---|---|---|---|---|---|
| Baseline | 35.0 ± 7.07 | 25.0 ± 0 | 29.5 ± 23.15 | 70.0 ± 0 | 52.5 ± 31.82 |
| Week 4 | 50.0 ± 21.21 | 70.0 ± 0 | 40.9 ± 0 | 100.0 ± 0 | 48.3 ± 45.37 |
| Week 12 | 45.0 ± 0 | 85.0 ± 0 | 58.0 ± 0 | 85.0 ± 0 | 45.0 ± 37.75 |
| Week 24 | 30.0 ± 0 | — | 55.6 ± 30.66 | 50.0 ± 0 | 53.3 ± 37.53 |
| Week 28 | 35.0 ± 0 | 35.0 ± 0 | 50.0 ± 70.71 | 95.0 ± 0 | 95.0 ± 0 |
| Week 40 | 35.0 ± 0 | 50.0 ± 0 | 37.5 ± 53.03 | 90.0 ± 0 | 80.0 ± 21.21 |
| Week 48 | — | — | 48.1 ± 39.27 | — | — |
| Week 72 | 30.0 ± 0 | 40.0 ± 0 | 40.6 ± 36.27 | 70.0 ± 0 | 95.0 ± 0 |
| Week 104 | — | 30.0 ± 0 | 58.2 ± 21.54 | 95.0 ± 0 | 70.0 ± 35.36 |
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.
| Score on a scale | MCS110 3 mg/kg (PART BC) | MCS110 5 mg/kg (PART BC) | MCS110 10 mg/kg (Part BC) | MCS110 3 mg/kg & MCS110 10mg/kg (PART BC) | MCS110 5 mg/kg & MCS110 10mg/kg (PART BC) |
|---|---|---|---|---|---|
| Baseline | 41.1 ± 12.63 | 50.0 ± 0 | 50.0 ± 16.44 | 50.0 ± 0 | 62.5 ± 27.78 |
| Week 4 | 58.9 ± 32.83 | 75.0 ± 0 | 59.4 ± 16.92 | 57.1 ± 0 | 57.1 ± 24.74 |
| Week 12 | 71.4 ± 0 | 78.6 ± 0 | 69.3 ± 21.31 | 64.3 ± 0 | 56.0 ± 26.33 |
| Week 24 | 50.0 ± 0 | — | 65.9 ± 25.45 | 67.9 ± 0 | 67.9 ± 0 |
| Week 28 | 60.7 ± 0 | 60.7 ± 0 | 62.5 ± 53.03 | 75.0 ± 0 | 89.3 ± 0 |
| Week 40 | 75.0 ± 0 | 64.3 ± 0 | 42.9 ± 60.61 | 78.6 ± 0 | 73.2 ± 37.88 |
| Week 48 | — | — | 62.1 ± 24.29 | — | — |
| Week 72 | 50.0 ± 0 | 57.1 ± 0 | 40.6 ± 28.43 | 78.6 ± 0 | 85.7 ± 0 |
| Week 104 | — | 53.6 ± 0 | 67.3 ± 20.63 | 85.7 ± 0 | 62.5 ± 32.83 |
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).
| Score on a scale | MCS110 3 mg/kg (PART BC) | MCS110 5 mg/kg (PART BC) | MCS110 10 mg/kg (Part BC) | MCS110 3 mg/kg & MCS110 10mg/kg (PART BC) | MCS110 5 mg/kg & MCS110 10mg/kg (PART BC) |
|---|---|---|---|---|---|
| Week 4 | 11.0 ± 1.41 | 3.7 ± 5.03 | 0.6 ± 25.07 | 1.3 ± 2.50 | 5.5 ± 10.85 |
| Week 24 | -1.0 ± 0.00 | 10.0 ± 0.00 | 9.5 ± 14.04 | 1.0 ± 8.54 | 9.8 ± 16.21 |
| Up to Week 104 | — | 1.3 ± 5.51 | 6.9 ± 13.93 | 7.0 ± 8.91 | 18.0 ± 25.63 |
Collected over Treatment-emergent adverse events .Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 2 years.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| MCS110 10 mg/kg (PART A) | 0/5 (0%) | 0/5 (0%) | 3/5 (60%) |
| Placebo (PART A) | 0/2 (0%) | 1/2 (50%) | 1/2 (50%) |
| MCS110 10mg/kg (PART B) | 0/11 (0%) | 2/11 (18.2%) | 11/11 (100%) |
| Placebo/10mg/kg (PART B) | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| MCS110 3mg/kg (PART C) | 0/7 (0%) | 3/7 (42.9%) | 7/7 (100%) |
| MCS110 5mg/kg (PART C) | 0/7 (0%) | 1/7 (14.3%) | 6/7 (85.7%) |
| MCS110 10mg/kg (PART C) | 0/12 (0%) | 4/12 (33.3%) | 11/12 (91.7%) |
| Event | MCS110 10 mg/kg (PART A) | Placebo (PART A) | MCS110 10mg/kg (PART B) | Placebo/10mg/kg (PART B) | MCS110 3mg/kg (PART C) | MCS110 5mg/kg (PART C) | MCS110 10mg/kg (PART C) |
|---|---|---|---|---|---|---|---|
| Cholecystitis acuteHepatobiliary disorders | 0/5 | 1/2 | 0/11 | 0/3 | 0/7 | 0/7 | 0/12 |
| Infusion related reactionInjury, poisoning and procedural complications | 0/5 | 0/2 | 0/11 | 0/3 | 2/7 | 0/7 | 0/12 |
| Haemoglobin decreasedInvestigations | 0/5 | 0/2 | 0/11 | 0/3 | 1/7 | 0/7 | 0/12 |
| DysarthriaNervous system disorders | 0/5 | 0/2 | 1/11 | 0/3 | 0/7 | 1/7 | 0/12 |
| Facial paralysisNervous system disorders | 0/5 | 0/2 | 0/11 | 0/3 | 0/7 | 1/7 | 0/12 |
| NauseaGastrointestinal disorders | 0/5 | 0/2 | 1/11 | 0/3 | 0/7 | 0/7 | 0/12 |
| Oesophageal spasmGastrointestinal disorders | 0/5 | 0/2 | 1/11 | 0/3 | 0/7 | 0/7 | 0/12 |
| VomitingGastrointestinal disorders | 0/5 | 0/2 | 1/11 | 0/3 | 0/7 | 0/7 | 0/12 |
| Gait disturbanceGeneral disorders | 0/5 | 0/2 | 1/11 | 0/3 | 0/7 | 0/7 | 0/12 |
| Non-cardiac chest painGeneral disorders | 0/5 | 0/2 | 1/11 | 0/3 | 0/7 | 0/7 | 0/12 |
| Event | MCS110 10 mg/kg (PART A) | Placebo (PART A) | MCS110 10mg/kg (PART B) | Placebo/10mg/kg (PART B) | MCS110 3mg/kg (PART C) | MCS110 5mg/kg (PART C) | MCS110 10mg/kg (PART C) |
|---|---|---|---|---|---|---|---|
| Periorbital oedemaEye disorders | 0/5 | 0/2 | 4/11 | 0/3 | 5/7 | 3/7 | 4/12 |
| FatigueGeneral disorders | 0/5 | 0/2 | 4/11 | 0/3 | 5/7 | 2/7 | 2/12 |
| NauseaGastrointestinal disorders | 0/5 | 1/2 | 5/11 | 0/3 | 1/7 | 3/7 | 1/12 |
| Blood creatine phosphokinase increasedInvestigations | 1/5 | 1/2 | 4/11 | 0/3 | 0/7 | 0/7 | 2/12 |
| Peripheral swellingGeneral disorders | 0/5 | 0/2 | 2/11 | 0/3 | 2/7 | 3/7 | 3/12 |
| Benign joint neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/5 | 0/2 | 4/11 | 0/3 | 0/7 | 3/7 | 2/12 |
| HeadacheNervous system disorders | 2/5 | 0/2 | 4/11 | 0/3 | 2/7 | 2/7 | 2/12 |
| DiarrhoeaGastrointestinal disorders | 0/5 | 0/2 | 4/11 | 0/3 | 0/7 | 0/7 | 0/12 |
| NasopharyngitisInfections and infestations | 0/5 | 0/2 | 4/11 | 0/3 | 1/7 | 2/7 | 3/12 |
| RashSkin and subcutaneous tissue disorders | 0/5 | 0/2 | 4/11 | 0/3 | 2/7 | 2/7 | 2/12 |
| Age, Continuous(Years) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 51.4 ± 8.96 | 30.0 ± 4.24 | 46.3 ± 10.14 | 26.7 ± 11.59 | 45.7 ± 17.93 | 38.0 ± 21.66 | 43.8 ± 13.38 | 46.3 ± 2.87 | 29.0 ± 6.06 | 41.3 ± 12.91 |
| Sex: Female, Male(Participants) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Female | 3 | 1 | 6 | 2 | 1 | 1 | 3 | 2 | 3 | 22 |
| Male | 2 | 1 | 2 | 1 | 2 | 2 | 1 | 2 | 1 | 14 |
| Race/Ethnicity, Customized(Participants) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Caucasian | 4 | 1 | 8 | 2 | 3 | 3 | 3 | 4 | 3 | 31 |
| Black | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 |
| Other | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 3 |
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