Clincosm LogoSign in Get a demo

MCS110 in Patients With Pigmented Villonodular Synovitis (PVNS)

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01643850
Collaborator
(none)
36
Enrollment
8
Locations
7
Arms
79.9
Actual Duration (Months)
4.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
36 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase II Randomized, Double -Blind, Placebo Controlled Study to Assess Safety, Tolerability and Effect on Tumor Size of MCS110 in Patients With Pigmented Villonodular Synovitis (PVNS)
Actual Study Start Date :
Apr 23, 2012
Actual Primary Completion Date :
Dec 7, 2017
Actual Study Completion Date :
Dec 21, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: MCS110

Participants will receive a single dose of 10mg/kg on day 1 administered by regular 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.
Other Names:
  • Intravenous infusion of MCS110.

    		•
    Placebo Comparator: Placebo

    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
    Participants will receive a single dose of NaCl on day 1 through intravenous infusion.
    Other Names:
  • Intravenous infusion of placebo.

    		•
    Experimental: MCS110 3 mg/kg

    Part C: MCS110 3 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.
    Other Names:
  • Intravenous infusion of MCS110.

    		•
    Experimental: MCS110 5 mg/kg

    Part C: MCS110 5 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.
    Other Names:
  • Intravenous infusion of MCS110.

    		•
    Experimental: MCS110 10 mg/kg

    Part C: 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.
    Other Names:
  • Intravenous infusion of MCS110.

    		•
    Experimental: MCS110 3 mg/kg & MCS110 10mg/kg

    Part C: MCS110 3 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.
    Other Names:
  • Intravenous infusion of MCS110.

    		•
    Experimental: MCS110 5 mg/kg & MCS110 10mg/kg

    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.
    Other Names:
  • Intravenous infusion of MCS110.

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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".

    2. 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".

    3. 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]

    4. 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].

    5. Number of Participants With Adverse Events [Approximately 2 years]

      Overall incidence of Adverse Events

    Secondary Outcome Measures

    1. 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).

    2. 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)

    3. 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)

    4. 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

    5. 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.

    6. 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

    7. 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".

    8. Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion [Week 24/28, Week 104]

      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].

    9. 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].

    10. 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.

    11. 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.

    12. 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.

    13. 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.

    14. 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.

    15. 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.

    16. 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.

    17. 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.

    18. 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.

    19. 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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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/exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site San Diego California United States 92103-8894
    2 Novartis Investigative Site Denver Colorado United States 80237
    3 Novartis Investigative Site Washington District of Columbia United States 20011
    4 Novartis Investigative Site Miami Florida United States 33136
    5 Novartis Investigative Site Chicago Illinois United States 60612
    6 Novartis Investigative Site Minneapolis Minnesota United States 55455
    7 Novartis Investigative Site Philadelphia Pennsylvania United States 19107
    8 Novartis Investigative Site Basel Switzerland 4056

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01643850
    Other Study ID Numbers:
    • CMCS110X2201
    • 2011-002951-32
    First Posted:
    Jul 18, 2012
    Last Update Posted:
    Jan 5, 2021
    Last Verified:
    Feb 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Pigmented Villonodular Synovitis
    PVNS
    Giant cell tumor of the tendon sheath
    GCCTS
    Tenosynovial giant cell tumor (localized or diffused type)
    GCTS
    MCS110
    Additional relevant MeSH terms:
    Neoplasms
    Giant Cell Tumors
    Giant Cell Tumor of Tendon Sheath
    Synovitis, Pigmented Villonodular
    Synovitis

    Study Results

    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.
    Pre-assignment Detail
    Arm/Group Title 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)
    Arm/Group Description Participants received a single dose of 10 mg/kg on Day 1 administered by i.v. infusion Participants received single dose placebo by i.v. infusion to match MCS110 10 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg. This group also included participants who had received placebo as a 1st dose 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 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 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 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 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. 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.
    Period Title: Overall Study
    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

    Baseline Characteristics

    Arm/Group Title 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
    Arm/Group Description Participants received a single dose of 10 mg/kg on Day 1 administered by i.v. infusion Participants received single dose placebo by i.v. infusion to match MCS110 10 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg. This group also included participants who had received placebo as a 1st dose 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 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 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 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 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. 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. Total of all reporting groups
    Overall Participants 5 2 8 3 3 3 4 4 4 36
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    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 (Count of Participants)
    Female
    3
    60%
    1
    50%
    6
    75%
    2
    66.7%
    1
    33.3%
    1
    33.3%
    3
    75%
    2
    50%
    3
    75%
    22
    61.1%
    Male
    2
    40%
    1
    50%
    2
    25%
    1
    33.3%
    2
    66.7%
    2
    66.7%
    1
    25%
    2
    50%
    1
    25%
    14
    38.9%
    Race/Ethnicity, Customized (Number) [Number]
    Caucasian
    4
    80%
    1
    50%
    8
    100%
    2
    66.7%
    3
    100%
    3
    100%
    3
    75%
    4
    100%
    3
    75%
    31
    86.1%
    Black
    1
    20%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    2
    5.6%
    Other
    0
    0%
    1
    50%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    3
    8.3%

    Outcome Measures

    1. Primary Outcome
    Title Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic Analysis Set
    Arm/Group Title Placebo (PART ABC4) MCS110 3 mg/kg (PART ABC4) MCS110 5 mg/kg (PART ABC4) MCS110 10 mg/kg (PART ABC4)
    Arm/Group Description Single dose placebo from PART A and B Single dose MCS110 3 mg/kg. This group included also the subjects who later switch to MCS110 10 mg/kg Single dose MCS110 5 mg/kg. This group included also the subjects who later switch to MCS110 10 mg/kg. Single dose MCS110 10 mg/kg
    Measure Participants 5 7 7 17
    Mean (Standard Deviation) [mm3]
    -4222.8
    (6284.56)
    -668.5
    (18751.44)
    -9998.4
    (15628.40)
    -38002.1
    (57314.73)
    2. Primary Outcome
    Title Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic Analysis Set
    Arm/Group Title Placebo (PART ABC4) MCS110 3 mg/kg (PART ABC4) MCS110 5 mg/kg (PART ABC4) MCS110 10 mg/kg (PART ABC4)
    Arm/Group Description Single dose placebo from PART A and B Single dose MCS110 3 mg/kg. This group included also the subjects who later switch to MCS110 10 mg/kg Single dose MCS110 5 mg/kg. This group included also the subjects who later switch to MCS110 10 mg/kg. Single dose MCS110 10 mg/kg
    Measure Participants 5 7 7 17
    Mean (Standard Deviation) [Percentage]
    -7.7
    (5.10)
    -7.4
    (13.21)
    -24.8
    (23.42)
    -32.6
    (16.61)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo (PART ABC4), MCS110 3 mg/kg (PART ABC4)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.915
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.98
    Confidence Interval (2-Sided) 95%
    0.71 to 1.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo (PART ABC4), MCS110 5 mg/kg (PART ABC4)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.117
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Median Difference (Net)
    Estimated Value 0.78
    Confidence Interval (2-Sided) 95%
    0.57 to 1.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo (PART ABC4), MCS110 10 mg/kg (PART ABC4)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.69
    Confidence Interval (2-Sided) 95%
    0.52 to 0.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Primary Outcome
    Title Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic Analysis Set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 3 mg/kg 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 Participants received multiple monthly doses of MCS110 10 mg/kg. This included patients who started with single dose placebo, then switched to MCS110 10mg/kg after they switched to MCS110 10mg/kg and had their baseline re-calculated. 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. Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 7 7 15 4 4
    Mean (Standard Deviation) [mm3]
    -2450.3
    (2721.24)
    -29164.3
    (23286.18)
    -37015.1
    (29297.02)
    -42420.1
    (63812.69)
    -3571.9
    (3612.97)
    4. Primary Outcome
    Title Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic Analysis Set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg. This included patients who started with single dose placebo, then switched to MCS110 10mg/kg after they switched to MCS110 10mg/kg and had their baseline re-calculated. Participants received 3 monthly doses of 3 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses) Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 7 7 15 4 4
    Mean (Standard Deviation) [Percentage]
    -29.7
    (33.73)
    -56.3
    (20.31)
    -55.0
    (19.02)
    -45.8
    (40.11)
    -22.6
    (16.21)
    5. Primary Outcome
    Title Number of Participants With Adverse Events
    Description Overall incidence of Adverse Events
    Time Frame Approximately 2 years

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set
    Arm/Group Title 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)
    Arm/Group Description Participants received a single dose of 10mg/kg on day 1 administered by i.v. infusion. Participants received single dose placebo to match MCS110 10mg/kg (i.v. infusion) Participants received multiple monthly doses of MCS110 10 mg/kg. This group also included participants who had received placebo as a 1st dose Participants received single dose placebo to match first dose of MCS110 10 mg/kg (i.v. infusion) and then continued with monthly administration of MCS110 10 mg/kg. Subset of MCS110 (Part B) Participants received multiple monthly doses of MCS110 3 mg/kg 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 Participants received multiple monthly doses of MCS110 10 mg/kg. This group includes also participants who had received before 3 monthly doses of 3 or 5 mg/kg and then switched to MCS110 10 mg/kg
    Measure Participants 5 2 11 3 7 7 12
    AEs of mild severity
    3
    60%
    1
    50%
    11
    137.5%
    1
    33.3%
    7
    233.3%
    6
    200%
    11
    275%
    AEs of moderate severity
    1
    20%
    1
    50%
    9
    112.5%
    2
    66.7%
    4
    133.3%
    2
    66.7%
    5
    125%
    AEs of severe severity
    0
    0%
    0
    0%
    4
    50%
    0
    0%
    2
    66.7%
    1
    33.3%
    4
    100%
    Study drug related AEs
    3
    60%
    1
    50%
    10
    125%
    1
    33.3%
    7
    233.3%
    5
    166.7%
    8
    200%
    Serious AEs
    0
    0%
    1
    50%
    2
    25%
    0
    0%
    3
    100%
    1
    33.3%
    4
    100%
    AEs leading to discontinuation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    66.7%
    1
    33.3%
    1
    25%
    6. Secondary Outcome
    Title Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title 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)
    Arm/Group Description Participants received a single dose of 10 mg/kg on Day 1 administered by i.v. infusion Participants received multiple monthly doses of MCS110 10 mg/kg. This group also included participants who had received placebo as a 1st dose Participants received single dose placebo to match first dose of MCS110 10 mg/kg (i.v. infusion)and then continued with monthly administration of MCS110 10 mg/kg. Participants could receive a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor growth again Participants received multiple monthly doses of MCS110 3 mg/kg. Participants could receive a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor growth again 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 Participants received multiple monthly doses of MCS110 10 mg/kg. Participants could receive a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor growth again
    Measure Participants 5 8 3 6 7 4
    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)
    7. Secondary Outcome
    Title Pharmacokinetics of MCS110 Maximum Concentration (Cmax)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title 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)
    Arm/Group Description Participants received a single dose of 10 mg/kg on Day 1 administered by i.v. infusion Participants received multiple monthly doses of MCS110 10 mg/kg. This group also included participants who had received placebo as a 1st dose Participants received single dose placebo to match first dose of MCS110 10 mg/kg (i.v. infusion)and then continued with monthly administration of MCS110 10 mg/kg. Participants could receive a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor growth again Participants received multiple monthly doses of MCS110 3 mg/kg. Participants could receive a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor growth again 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 Participants received multiple monthly doses of MCS110 10 mg/kg. Participants could receive a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor growth again
    Measure Participants 5 8 3 6 7 4
    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)
    8. Secondary Outcome
    Title Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title 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)
    Arm/Group Description Participants received a single dose of 10 mg/kg on Day 1 administered by i.v. infusion Participants received multiple monthly doses of MCS110 10 mg/kg. This group also included participants who had received placebo as a 1st dose Participants received single dose placebo to match first dose of MCS110 10 mg/kg (i.v. infusion)and then continued with monthly administration of MCS110 10 mg/kg. Participants could receive a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor growth again Participants received multiple monthly doses of MCS110 3 mg/kg. Participants could receive a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor growth again 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 Participants received multiple monthly doses of MCS110 10 mg/kg. Participants could receive a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor growth again
    Measure Participants 5 8 3 6 7 4
    Day 1
    2.083
    1.192
    3.125
    5
    4
    Day 29
    1.467
    Day 85
    1.25
    3.533
    1.233
    Day 112
    3.1
    9. Secondary Outcome
    Title Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic Analysis Set
    Arm/Group Title 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)
    Arm/Group Description Participants received a single dose of 10 mg/kg on Day 1 administered by i.v. infusion Participants received single dose placebo to match MCS110 10 mg/k Participants received multiple monthly doses of MCS110 10 mg/kg. This group also included participants who had received placebo as a 1st dose Participants received single dose placebo to match first dose of MCS110 10 mg/kg (i.v. infusion)and then continued with monthly administration of MCS110 10 mg/kg. Participants could receive a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor growth again Participants received multiple monthly doses of MCS110 3 mg/kg. Participants could receive a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor growth again 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 Participants received multiple monthly doses of MCS110 10 mg/kg. Participants could receive a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor growth again
    Measure Participants 5 2 8 3 6 7 4
    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)
    10. Secondary Outcome
    Title Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I).
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis
    Arm/Group Title MCS110 10 mg/kg (PART ABC4) Placebo (PARTS A and B) MCS110 10 mg/kg (PART BC)
    Arm/Group Description Participants received a single dose of MCS110 10 mg/kg PART A: Participants received single dose placebo to match MCS110 10mg/kg (i.v. infusion). PART B: Participants received single dose placebo to match first dose of MCS110 10 mg/kg (i.v. infusion) and then continued with monthly administration of MCS110 10 mg/kg. Participants received multiple monthly doses of MCS110 10 mg/kg. This included patients who started with single dose placebo, then switched to MCS110 10mg/kg after they switched to MCS110 10mg/kg and had their baseline re-calculated.
    Measure Participants 17 5 17
    Baseline
    0.3
    0.5
    0.4
    Week 4
    0.1
    0.6
    0.1
    Week 24
    0.1
    Week 104
    0.3
    11. Secondary Outcome
    Title Number of Participants With Negative Anti-MCS110 Antibody
    Description To assess the immunogenicity of MCS110 in serum anti-MCS110 antibody concentrations
    Time Frame Baseline, throughout the study up to Day 505

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received a single dose of 10mg/kg on day 1 administered by regular infusion. Participants received single dose placebo to match MCS110 10 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg. This group also included participants who had received placebo as a 1st dose Participants received single dose placebo to match first dose of MCS110 10 mg/kg (i.v. infusion) and then continued with monthly administration of MCS110 10 mg/kg Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg 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. 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 patients who started with a dose of 5 mg/kg
    Measure Participants 5 2 8 3 3 4 4 4 4
    Baseline
    5
    100%
    1
    50%
    8
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    75%
    4
    100%
    4
    100%
    Day 29
    4
    80%
    2
    100%
    8
    100%
    3
    100%
    2
    66.7%
    4
    133.3%
    4
    100%
    4
    100%
    3
    75%
    Day 85
    3
    60%
    2
    100%
    7
    87.5%
    3
    100%
    1
    33.3%
    3
    100%
    3
    75%
    3
    75%
    4
    100%
    Day 127
    3
    60%
    1
    50%
    Day 169
    4
    80%
    2
    100%
    7
    87.5%
    1
    33.3%
    1
    33.3%
    3
    100%
    3
    75%
    3
    75%
    4
    100%
    Day 336
    7
    140%
    2
    100%
    Day 393
    1
    20%
    2
    100%
    4
    50%
    4
    133.3%
    2
    66.7%
    Day 505
    6
    120%
    1
    50%
    4
    50%
    4
    133.3%
    3
    100%
    2
    66.7%
    12. Secondary Outcome
    Title Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic Analysis Set
    Arm/Group Title Placebo (PART ABC4) MCS110 3 mg/kg (PART ABC4) MCS110 5 mg/kg (PART ABC4) MCS110 10 mg/kg (PART ABC4)
    Arm/Group Description Single dose placebo from PART A and B Single dose MCS110 3 mg/kg. This group included also the subjects who later switch to MCS110 10 mg/kg Single dose MCS110 5 mg/kg. This group included also the subjects who later switch to MCS110 10 mg/kg. Single dose MCS110 10 mg/kg
    Measure Participants 5 7 7 17
    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)
    13. Secondary Outcome
    Title Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg Participants received 3 monthly doses of 3 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses) Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 7 7 15 4 4
    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)
    14. Secondary Outcome
    Title Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg. This included patients who started with single dose placebo, then switched to MCS110 10mg/kg after they switched to MCS110 10mg/kg and had their baseline re-calculated. Participants received 3 monthly doses of 3 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses) Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 3 3 15 4 4
    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)
    15. Secondary Outcome
    Title Time to Relapse
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 10 mg/kg Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/k. Participants could have received a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor grew again Participants received multiple monthly doses of MCS110 10 mg/kg Participants received 3 monthly doses of 3 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 11 3 3 4 4 4
    Mean (Standard Deviation) [Days]
    337.0
    (108.89)
    454.0
    (0)
    477.0
    (0)
    296.0
    (103.24)
    NA
    (NA)
    NA
    (NA)
    16. Secondary Outcome
    Title Time to Surgery
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 10 mg/kg Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/k. Participants could have received a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor grew again Participants received multiple monthly doses of MCS110 10 mg/kg Participants received 3 monthly doses of 3 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 11 3 3 3 4 4
    Mean (Standard Deviation) [Days]
    387.0
    (116.25)
    0
    (0)
    0
    (0)
    231.0
    (0)
    NA
    (NA)
    NA
    (NA)
    17. Secondary Outcome
    Title Average of Health-Related Quality of Life Questionnaire Score for mHAQ
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg Participants received 3 monthly doses of 3 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses) Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 3 3 15 4 4
    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)
    18. Secondary Outcome
    Title Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received a single dose of 10mg/kg on day 1 administered by regular infusion. Participants received multiple monthly doses of MCS110 10 mg/kg. This group also included participants who had received placebo as a 1st dose Participants received multiple monthly doses of MCS110 5 mg/kg Participants received multiple monthly doses of MCS110 5 mg/k. Participants could have received a 2nd treatment cycle (6 x 10 mg/kg MCS110) if tumor grew again Participants received multiple monthly doses of MCS110 10 mg/kg ) 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 patients who started with a dose of 3 mg/kg 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 patients who started with a dose of 5 mg/kg
    Measure Participants 5 8 3 3 4 4 4
    Number [Number of Monocytes]
    NA
    NA
    NA
    NA
    NA
    NA
    NA
    19. Secondary Outcome
    Title Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg Participants received 3 monthly doses of 3 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses) Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 3 3 15 4 4
    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)
    20. Secondary Outcome
    Title Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg Participants received 3 monthly doses of 3 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses) Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 3 3 15 4 4
    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)
    21. Secondary Outcome
    Title Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg Participants received 3 monthly doses of 3 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses) Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 3 3 15 4 4
    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)
    22. Secondary Outcome
    Title Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg Participants received 3 monthly doses of 3 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses) Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 3 3 15 4 4
    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)
    23. Secondary Outcome
    Title Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg Participants received 3 monthly doses of 3 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses) Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 3 3 15 4 4
    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)
    24. Secondary Outcome
    Title Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Pharmacodynamic analysis set
    Arm/Group Title 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)
    Arm/Group Description Participants received multiple monthly doses of MCS110 3 mg/kg Participants received multiple monthly doses of MCS110 5 mg/kg Participants received multiple monthly doses of MCS110 10 mg/kg Participants received 3 monthly doses of 3 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses) Participants received 3 monthly doses of 5 mg/kg and switched to monthly doses of 10 mg/kg (max 3 doses)
    Measure Participants 3 3 15 4 4
    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)

    Adverse Events

    Time Frame 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.
    Adverse Event Reporting Description
    Arm/Group Title 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)
    Arm/Group Description Participants received a single dose of 10 mg/kg on Day 1 administered by i.v. infusion Participants received single dose placebo by i.v. infusion to match MCS110 10 mg/kg MCS110 10 mg/kg (i.v. infusion) 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 MCS110 3 mg/kg (i.v. infusion) MCS110 5 mg/kg (i.v. infusion) MCS110 10 mg/kg (i.v. infusion)
    All Cause Mortality
    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)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Serious Adverse Events
    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)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/5 (0%) 1/2 (50%) 2/11 (18.2%) 0/3 (0%) 3/7 (42.9%) 1/7 (14.3%) 4/12 (33.3%)
    Gastrointestinal disorders
    Nausea 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Oesophageal spasm 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Vomiting 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    General disorders
    Gait disturbance 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Non-cardiac chest pain 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Pain 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Pyrexia 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Hepatobiliary disorders
    Cholecystitis acute 0/5 (0%) 1/2 (50%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Infections and infestations
    Laryngitis 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Meningoencephalitis viral 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Streptococcal bacteraemia 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Viral infection 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Injury, poisoning and procedural complications
    Infusion related reaction 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 2/7 (28.6%) 0/7 (0%) 0/12 (0%)
    Investigations
    Alanine aminotransferase increased 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Aspartate aminotransferase increased 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Blood creatine phosphokinase increased 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Electrocardiogram ST segment depression 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Haemoglobin decreased 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Nervous system disorders
    Dizziness 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Dysarthria 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Facial paralysis 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Product Issues
    Device dislocation 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Nasal congestion 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Other (Not Including Serious) Adverse Events
    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)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/5 (60%) 1/2 (50%) 11/11 (100%) 3/3 (100%) 7/7 (100%) 6/7 (85.7%) 11/12 (91.7%)
    Blood and lymphatic system disorders
    Iron deficiency anaemia 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 1/12 (8.3%)
    Leukopenia 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Lymphadenopathy 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Neutropenia 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Cardiac disorders
    Pericardial effusion 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Ear and labyrinth disorders
    Ear pain 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Endocrine disorders
    Autoimmune thyroiditis 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Eye disorders
    Blepharitis 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Dark circles under eyes 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Eye pruritus 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Eye swelling 0/5 (0%) 0/2 (0%) 3/11 (27.3%) 0/3 (0%) 1/7 (14.3%) 1/7 (14.3%) 0/12 (0%)
    Eyelid oedema 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Papilloedema 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Periorbital oedema 0/5 (0%) 0/2 (0%) 4/11 (36.4%) 0/3 (0%) 5/7 (71.4%) 3/7 (42.9%) 4/12 (33.3%)
    Periorbital swelling 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 1/12 (8.3%)
    Gastrointestinal disorders
    Abdominal pain 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Dental caries 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Diarrhoea 0/5 (0%) 0/2 (0%) 4/11 (36.4%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Haematochezia 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Haemorrhoidal haemorrhage 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Nausea 0/5 (0%) 1/2 (50%) 5/11 (45.5%) 0/3 (0%) 1/7 (14.3%) 3/7 (42.9%) 1/12 (8.3%)
    Stomatitis 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Vomiting 0/5 (0%) 0/2 (0%) 3/11 (27.3%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    General disorders
    Administration site rash 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Chills 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Face oedema 1/5 (20%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Fatigue 0/5 (0%) 0/2 (0%) 4/11 (36.4%) 0/3 (0%) 5/7 (71.4%) 2/7 (28.6%) 2/12 (16.7%)
    Infusion site pain 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Non-cardiac chest pain 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Oedema peripheral 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 1/3 (33.3%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Pain 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Peripheral swelling 0/5 (0%) 0/2 (0%) 2/11 (18.2%) 0/3 (0%) 2/7 (28.6%) 3/7 (42.9%) 3/12 (25%)
    Pyrexia 0/5 (0%) 0/2 (0%) 3/11 (27.3%) 0/3 (0%) 2/7 (28.6%) 0/7 (0%) 0/12 (0%)
    Soft tissue inflammation 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Swelling 0/5 (0%) 0/2 (0%) 2/11 (18.2%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Immune system disorders
    Drug hypersensitivity 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Seasonal allergy 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Infections and infestations
    Cellulitis 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Conjunctivitis 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Gastroenteritis 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Gastroenteritis norovirus 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Herpes zoster 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Influenza 1/5 (20%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Nasopharyngitis 0/5 (0%) 0/2 (0%) 4/11 (36.4%) 0/3 (0%) 1/7 (14.3%) 2/7 (28.6%) 3/12 (25%)
    Peritonsillitis 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Sinusitis 1/5 (20%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Subcutaneous abscess 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Tonsillitis 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Upper respiratory tract infection 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 1/3 (33.3%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Urinary tract infection 0/5 (0%) 0/2 (0%) 2/11 (18.2%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Viral infection 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Injury, poisoning and procedural complications
    Contusion 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Fall 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Fibula fracture 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Foot fracture 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Infusion related reaction 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 1/7 (14.3%) 2/12 (16.7%)
    Procedural dizziness 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Investigations
    Alanine aminotransferase increased 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Amylase increased 1/5 (20%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 2/12 (16.7%)
    Antinuclear antibody positive 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Aspartate aminotransferase increased 1/5 (20%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 2/12 (16.7%)
    Blood cholesterol increased 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Blood creatine phosphokinase increased 1/5 (20%) 1/2 (50%) 4/11 (36.4%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 2/12 (16.7%)
    Blood lactate dehydrogenase increased 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Blood pressure increased 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Blood triglycerides increased 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Gamma-glutamyltransferase increased 1/5 (20%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Haemoglobin decreased 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Lipase increased 1/5 (20%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 2/12 (16.7%)
    Metabolism and nutrition disorders
    Decreased appetite 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Dehydration 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Fluid retention 0/5 (0%) 0/2 (0%) 2/11 (18.2%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 1/3 (33.3%) 2/7 (28.6%) 2/7 (28.6%) 2/12 (16.7%)
    Arthritis 1/5 (20%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Joint stiffness 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Joint swelling 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 1/3 (33.3%) 1/7 (14.3%) 0/7 (0%) 3/12 (25%)
    Muscle spasms 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Myalgia 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Neck pain 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Pain in extremity 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 2/7 (28.6%) 0/12 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign joint neoplasm 1/5 (20%) 0/2 (0%) 4/11 (36.4%) 0/3 (0%) 0/7 (0%) 3/7 (42.9%) 2/12 (16.7%)
    Nervous system disorders
    Dizziness 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Headache 2/5 (40%) 0/2 (0%) 4/11 (36.4%) 0/3 (0%) 2/7 (28.6%) 2/7 (28.6%) 2/12 (16.7%)
    Hypoaesthesia 1/5 (20%) 0/2 (0%) 2/11 (18.2%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Intracranial pressure increased 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Migraine 0/5 (0%) 0/2 (0%) 2/11 (18.2%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 1/12 (8.3%)
    Paraesthesia 0/5 (0%) 0/2 (0%) 2/11 (18.2%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Sciatica 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Psychiatric disorders
    Anxiety 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Depression 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Mental status changes 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Reproductive system and breast disorders
    Menstrual disorder 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Cough 0/5 (0%) 0/2 (0%) 3/11 (27.3%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 1/12 (8.3%)
    Epistaxis 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Oropharyngeal pain 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Skin and subcutaneous tissue disorders
    Acne 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Alopecia 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Dermal cyst 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 1/7 (14.3%) 0/7 (0%) 0/12 (0%)
    Dermatitis acneiform 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Eczema 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Erythema nodosum 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Hyperhidrosis 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Pruritus 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Pruritus generalised 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Psoriasis 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Rash 0/5 (0%) 0/2 (0%) 4/11 (36.4%) 0/3 (0%) 2/7 (28.6%) 2/7 (28.6%) 2/12 (16.7%)
    Rash generalised 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 1/12 (8.3%)
    Skin wrinkling 0/5 (0%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Swelling face 0/5 (0%) 0/2 (0%) 3/11 (27.3%) 0/3 (0%) 1/7 (14.3%) 1/7 (14.3%) 1/12 (8.3%)
    Vascular disorders
    Hot flush 0/5 (0%) 0/2 (0%) 1/11 (9.1%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)
    Hypertension 0/5 (0%) 0/2 (0%) 2/11 (18.2%) 0/3 (0%) 0/7 (0%) 1/7 (14.3%) 0/12 (0%)
    Hypotension 1/5 (20%) 0/2 (0%) 0/11 (0%) 0/3 (0%) 0/7 (0%) 0/7 (0%) 0/12 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email Novartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01643850
    Other Study ID Numbers:
    • CMCS110X2201
    • 2011-002951-32
    First Posted:
    Jul 18, 2012
    Last Update Posted:
    Jan 5, 2021
    Last Verified:
    Feb 1, 2020