Pigmented Villonodular SynovitisPhase 2NCT01643850

MCS110 in Patients With Pigmented Villonodular Synovitis (PVNS)

A Phase 2 study testing MCS110 in people with Pigmented Villonodular Synovitis and PVNS, run by Novartis Pharmaceuticals at 8 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 12 years and older
Conditions the study is for: Pigmented Villonodular Synovitis, PVNS, Giant Cell Tumor of the Tendon Sheath
What is being tested?: MCS110
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 36 participants
Where: 8 sitesin 2 countries
Study dates: 23 Apr 2012to 21 Dec 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

8 sites in 2 countries.

Country

City, postcode or hospital

8 sites in 2 countries

United States7 sites

Novartis Investigative Site
Chicago, Illinois, 60612
Novartis Investigative Site
Denver, Colorado, 80237
Novartis Investigative Site
Miami, Florida, 33136
Novartis Investigative Site
Minneapolis, Minnesota, 55455
Novartis Investigative Site
Philadelphia, Pennsylvania, 19107
Novartis Investigative Site
San Diego, California, 92103-8894
Novartis Investigative Site
Washington D.C., District of Columbia, 20011

Other trials in United States

Switzerland1 site

Novartis Investigative Site
Basel, 4056

Other trials in Switzerland

About this study

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)

Conditions: Pigmented Villonodular Synovitis, PVNS, Giant Cell Tumor of the Tendon Sheath, GCCTS, Tenosynovial Giant Cell Tumor Localized or Diffused Type, GCTS
Being tested: MCS110, Placebo
Keywords: Pigmented Villonodular Synovitis, PVNS, Giant cell tumor of the tendon sheath, GCCTS, Tenosynovial giant cell tumor (localized or diffused type), GCTS, MCS110
Medical subject headings: Synovitis, Pigmented Villonodular, Giant Cell Tumor of Tendon Sheath

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MCS110Drug
Also called Intravenous infusion of 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.
PlaceboDrug
Also called Intravenous infusion of placebo.
Participants will receive a single dose of NaCl on day 1 through intravenous infusion.

Study groups in NCT01643850
Study group	Role	What they receive
MCS110	Experimental	Participants will receive a single dose of 10mg/kg on day 1 administered by regular infusion. Receives: Drug: MCS110
Placebo	Placebo comparator	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) Receives: Drug: Placebo
MCS110 3 mg/kg	Experimental	Part C: MCS110 3 mg/kg (i.v. infusion) Receives: Drug: MCS110
MCS110 5 mg/kg	Experimental	Part C: MCS110 5 mg/kg (i.v. infusion) Receives: Drug: MCS110
MCS110 10 mg/kg	Experimental	Part C: MCS110 10 mg/kg (i.v. infusion) Receives: Drug: MCS110
MCS110 3 mg/kg & MCS110 10mg/kg	Experimental	Part C: MCS110 3 mg/kg (i.v. infusion) \& MCS110 10 mg/kg (i.v. infusion) Receives: Drug: MCS110
MCS110 5 mg/kg & MCS110 10mg/kg	Experimental	Part C: MCS110 5 mg/kg (i.v. infusion) \& MCS110 10 mg/kg (i.v. infusion) Receives: Drug: MCS110

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size
To assess the efficacy of a single i.v. dose of MCS110 in changing the size of PVNS tumors (as compared to baseline) compared to placebo over 4 weeks evaluated by volume of PVNS tumors by 3-dimensional MRI. This analysis includes all data from patients 4 weeks after receiving the first dose of MCS110 (3, 5 or 10 mg/kg) or placebo and assesses the tumor volume changes at week 4 as compared to baseline. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called "ABC4".
Measured: Week 4
Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size
To assess the efficacy of a single i.v. dose of MCS110 in percent change of the PVNS tumor volume at week 4 as compared to baseline and compared to placebo evaluated by volume of PVNS tumors by 3-dimensional MRI. This analysis includes all data from patients who received at least a single dose of MCS110 (3, 5 or 10 mg/kg) or placebo and assesses the tumor volume changes at week 4 as compared to baseline. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called "ABC4".
Measured: Week 4
Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size
Assessment of maximum efficacy (multiple i.v.monthly doses (2 to 6) of 3, 5 or 10 mg/kg MCS110 or 3 \& 10 mg/kg or 5 \& 10 mg/kg in changing PVNS tumor volume (as compared to baseline) up to 8 weeks post last dose evaluated by MRI. Analysis included data starting from 1st dose of MCS110 in all treatment groups of Parts B and C. Part B patients who received placebo as 1st dose, measurement prior to receiving first dose of MCS110, was used as baseline and assessment time-points were adjusted accordingly. For Part C, participants starting treatment with low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and tumor volume reduction was ≤ 45%. Analysis includes data from patients who received at least 2 doses. The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg [3/10 mg/kg] or after 3 doses of 5 mg/kg to 10 mg/kg [5/10 mg/kg]
Measured: Up to 8 weeks post last dose
Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size
To assess the maximum efficacy of multiple monthly i.v. doses (2 to 6) of 3, 5 or 10 mg/kg MCS110 or 3 and 10 mg/kg or 5 and 10 mg/kg by percent change in the PVNS tumor volume (as compared to baseline) up to 8 weeks post last dose evaluated by MRI. Subjects starting treatment with a low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and the tumor volume reduction was ≤ 45%. This analysis includes data from all participants who received at least 2 doses of MCS110 and thus includes only patients from Part B and C of the study, thus the data set is called "Part BC". The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg [3/10 mg/kg] or after 3 doses of 5 mg/kg to 10 mg/kg [5/10 mg/kg].
Measured: Up to 8 weeks post last dose
Number of Participants With Adverse Events
Overall incidence of Adverse Events
Measured: Approximately 2 years

Secondary outcomes (19)

Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC)
Pharmacokinetic for a single dose of MCS110 for serum concentration -time curve (AUC).
Measured: Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr)
Pharmacokinetics of MCS110 Maximum Concentration (Cmax)
Pharmacokinetic characterization of a single dose of MCS110 for maximum serum concentration (Cmax)
Measured: Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr)
Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax)
Pharmacokinetic characterization of a single dose of MCS110 for time to maximum concentration (Tmax)
Measured: Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr)
Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time
Pharmacokinetic characterization of a single dose of MCS110 for evaluation of macrophage-colony stimulating factor (M-CSF) plasma concentrations over time
Measured: Baseline, Day 1, Day 85, Day 169
Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I).
Pharmacodynamic characterization of a single dose of MCS110 by measuring C-terminal telopeptide of Type 1 Collagen peptide (CTX-I), a biomarker of bone resorption. Data measured in participants from three arms: participants from Part A, B and C who received a single dose of 10 mg/kg and had assessment at week 4 (Part ABC4); participants from Part A and B who received placebo ; and participants from Part B and C who received multiple monthly doses of MCS110 (10 mg/kg.) Serum CTX-I data were generated in Part A and Part B. In Part C, samples were collected for serum bone CTX-I analysis. The analysis was not performed, as enough information on compound mode of action was obtained using creatine kinase (CK) and monocytes (hematology) data. Only data from 10mg/kg (single and multiple doses) are available.
Measured: Baseline, Week 4, Week 24, Week 104
Number of Participants With Negative Anti-MCS110 Antibody
To assess the immunogenicity of MCS110 in serum anti-MCS110 antibody concentrations
Measured: Baseline, throughout the study up to Day 505
Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion
To assess the clinical response of joint range of motion following a single i.v. dose of MCS110 or placebo as compared to baseline 4 weeks post-dose evaluated in participants, who had a knee tumor, which was the majority of participants (75%). The analysis includes all data from patients 4 weeks after receiving the first dose of MCS110 (3, 5 or 10 mg/kg) or placebo. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called "ABC4".
Measured: Week 4
Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion
To assess the clinical response of joint range of motion following multiple dose treatment with MCS110 3, 5, or 10 mg/kg evaluated in participants with knee tumor, which was the majority of participants (75%). The data presented are changes from baseline in degree. Participants, who started treatment with a low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and the tumor volume reduction was ≤ 45%. This analysis includes data from participants with knee tumor who received at least 2 doses of MCS110 and thus includes only patients from Part B and C of the study, thus the data set is called "Part BC". The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg [3/10 mg/kg] or after 3 doses of 5 mg/kg to 10 mg/kg [5/10 mg/kg].
Measured: Week 24/28, Week 104
Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS)
Measurement of the participant's pain with a 100 mm visual analog scale (VAS) following treatment with MCS110 3, 5, or 10 mg/kg evaluated. Data presented are changes from baseline in degree. Participants were asked to place a line perpendicular to the VAS line at the point that represented her/his pain intensity. Using a ruler, the score was determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor and the participants mark, providing a score from 0-100. Analysis includes data from participants with knee tumor who received at least 2 doses of MCS110 and thus includes only patients from Part B and C of the study, thus the data set is called "Part BC". The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg [3/10 mg/kg] or after 3 doses of 5 mg/kg to 10 mg/kg [5/10 mg/kg].
Measured: Baseline, Week 4, Week 12, Week 24, Week 28, Week 40, Week 48, Week 104
Time to Relapse
Time to relapse describes the time frame from baseline when the tumor volume increases again after the treatment with MCS110. To be considered a relapse tumor volume had to increase greater than 50% of the difference between tumor volume at baseline and the lowest tumor volume measured by MRI. In this assessment the Part B and Part C patients were analyzed separately. N/A (not available):Data analysis not performed as sample size was not analyzable as no patient had surgery/relapse.
Measured: Up to Week 104
Time to Surgery
Time to surgery describes the time frame from baseline to the time point when participants had surgical removement of PVNS tumor. This could be either residual tumor after the tumor volume was reduced or surgery due to relapse. In this assessment the Part B and Part C patients were analyzed separately. Not Available (NA): Data analysis not performed as sample size was not analyzable as no patient had surgery.
Measured: Up to Week 104
Average of Health-Related Quality of Life Questionnaire Score for mHAQ
The mHAQ assesses 20 activities in 8 categories related to daily life, which are rated on a 4-point Likert scale. The mHAQ is calculated as the average of the single scores with the following scoring: without difficulty =0; with some difficulty =1; with much difficulty =2; unable to do =3. Total score is between 0 - 3.0. Values <0.3 are considered normal. Data presented include only participants, who received multiple doses of MCS110.
Measured: up to 104 weeks
Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes
Blood samples were collected for the evaluation of CD14+ monocytes (using FACS) and CD14+ CD16+ monocytes. Based on preliminary analysis, the quality of the samples did not allow meaningful conclusions to be drawn. Thus, in Part B, the monocyte sample collection was discontinued.
Measured: Baseline Up to Week 104
Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life (QOL), pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor.
Measured: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life, pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor.
Measured: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life, pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor.
Measured: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life, pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor.
Measured: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
The KOOS is a patient-reported outcome measurement instrument developed to assess the subject's opinion about their knee and associated problems. The KOOS questionnaire collected data on 5 knee-specific patient-centered outcomes: activities of daily life (ADL), knee related quality of life, pain and discomfort, sport/recreation, symptoms. The 5 KOOS sub-scales were scored separately on a Likert scale scored from 0 (no problems) to 4 (extreme problems) and scores were transformed to a 0.100 scale with 0 representing extreme knee problems and 100 representing no problems. The 5 dimensions were analyzed independently. Positive changes (i.e. increases in the score) are beneficial. KOOS was assessed in Part B and C only in participants with knee PVNS tumor.
Measured: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire
The EQ-5D is a standardized measure of health status. The EQ visual analogue scale (EQ VAS)has a range from 0-100: worst possible to perfect health. Data show the absolute change from baseline of EQ5D VAS and at the different visits for participants, who received multiple doses of MCS110. (PART B and PART C).
Measured: Week 4, Week 24, up to 104 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Apr 201221 Dec 2018

First posted18 Jul 2012 (estimated)
Study start23 Apr 2012
Primary completion7 Dec 2017
Study completion21 Dec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pigmented Villonodular SynovitisStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01643850
Sponsor's protocol ID: CMCS110X2201
Other IDs: 2011-002951-32
Status last verified: Feb 2020
First submitted: 8 Mar 2012
Last updated: 5 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

Blay JY, El Sayadi H, Thiesse P, Garret J, Ray-Coquard I. Complete response to imatinib in relapsing pigmented villonodular synovitis/tenosynovial giant cell tumor (PVNS/TGCT). Ann Oncol. 2008 Apr;19(4):821-2. doi: 10.1093/annonc/mdn033. Epub 2008 Feb 21. No abstract available.
PubMed 18296418

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT01643850
Acronym / sponsor ID: CMCS110X2201
Conditions: Pigmented Villonodular Synovitis, PVNS, Giant Cell Tumor of the Tendon Sheath, GCCTS, Tenosynovial Giant Cell Tumor Localized or Diffused Type, GCTS
Keywords: Pigmented Villonodular Synovitis, PVNS, Giant cell tumor of the tendon sheath, GCCTS, Tenosynovial giant cell tumor (localized or diffused type), GCTS, MCS110
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 23 Apr 2012 (actual)
Primary completion: 7 Dec 2017 (actual)
Study completion: 21 Dec 2018 (actual)
First posted: 18 Jul 2012 (estimated)
Results: Posted 27 Feb 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 7

Arm	Type	Receives
MCS110	Experimental	Drug: MCS110Participants will receive a single dose of 10mg/kg on day 1 administered by regular infusion.
Placebo	Placebo comparator	Drug: PlaceboPart 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)
MCS110 3 mg/kg	Experimental	Drug: MCS110Part C: MCS110 3 mg/kg (i.v. infusion)
MCS110 5 mg/kg	Experimental	Drug: MCS110Part C: MCS110 5 mg/kg (i.v. infusion)
MCS110 10 mg/kg	Experimental	Drug: MCS110Part C: MCS110 10 mg/kg (i.v. infusion)
MCS110 3 mg/kg & MCS110 10mg/kg	Experimental	Drug: MCS110Part C: MCS110 3 mg/kg (i.v. infusion) \& MCS110 10 mg/kg (i.v. infusion)
MCS110 5 mg/kg & MCS110 10mg/kg	Experimental	Drug: MCS110Part C: MCS110 5 mg/kg (i.v. infusion) \& MCS110 10 mg/kg (i.v. infusion)

Who may qualify

Ages: 12 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (12 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MCS110Also: Intravenous infusion of 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.	Drug	MCS110, MCS110 10 mg/kg, MCS110 3 mg/kg, MCS110 3 mg/kg & MCS110 10mg/kg, MCS110 5 mg/kg, MCS110 5 mg/kg & MCS110 10mg/kg
PlaceboAlso: Intravenous infusion of placebo.Participants will receive a single dose of NaCl on day 1 through intravenous infusion.	Drug	Placebo

Primary outcome

Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size
Time frame: Week 4
To assess the efficacy of a single i.v. dose of MCS110 in changing the size of PVNS tumors (as compared to baseline) compared to placebo over 4 weeks evaluated by volume of PVNS tumors by 3-dimensional MRI. This analysis includes all data from patients 4 weeks after receiving the first dose of MCS110 (3, 5 or 10 mg/kg) or placebo and assesses the tumor volume changes at week 4 as compared to baseline. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called "ABC4".
Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size
Time frame: Week 4
To assess the efficacy of a single i.v. dose of MCS110 in percent change of the PVNS tumor volume at week 4 as compared to baseline and compared to placebo evaluated by volume of PVNS tumors by 3-dimensional MRI. This analysis includes all data from patients who received at least a single dose of MCS110 (3, 5 or 10 mg/kg) or placebo and assesses the tumor volume changes at week 4 as compared to baseline. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called "ABC4".
Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size
Time frame: Up to 8 weeks post last dose
Assessment of maximum efficacy (multiple i.v.monthly doses (2 to 6) of 3, 5 or 10 mg/kg MCS110 or 3 \& 10 mg/kg or 5 \& 10 mg/kg in changing PVNS tumor volume (as compared to baseline) up to 8 weeks post last dose evaluated by MRI. Analysis included data starting from 1st dose of MCS110 in all treatment groups of Parts B and C. Part B patients who received placebo as 1st dose, measurement prior to receiving first dose of MCS110, was used as baseline and assessment time-points were adjusted accordingly. For Part C, participants starting treatment with low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and tumor volume reduction was ≤ 45%. Analysis includes data from patients who received at least 2 doses. The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg [3/10 mg/kg] or after 3 doses of 5 mg/kg to 10 mg/kg [5/10 mg/kg]
Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size
Time frame: Up to 8 weeks post last dose
To assess the maximum efficacy of multiple monthly i.v. doses (2 to 6) of 3, 5 or 10 mg/kg MCS110 or 3 and 10 mg/kg or 5 and 10 mg/kg by percent change in the PVNS tumor volume (as compared to baseline) up to 8 weeks post last dose evaluated by MRI. Subjects starting treatment with a low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and the tumor volume reduction was ≤ 45%. This analysis includes data from all participants who received at least 2 doses of MCS110 and thus includes only patients from Part B and C of the study, thus the data set is called "Part BC". The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg [3/10 mg/kg] or after 3 doses of 5 mg/kg to 10 mg/kg [5/10 mg/kg].
Number of Participants With Adverse Events
Time frame: Approximately 2 years
Overall incidence of Adverse Events

19 secondary outcomes

Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC)
Time frame: Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr)
Pharmacokinetics of MCS110 Maximum Concentration (Cmax)
Time frame: Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr)
Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax)
Time frame: Day 1 (0 - 5 hr), Day 29, Day 85, Day 112, PART B (Day 1: (0 -5 hr), (Day 85: 0 - 5 hr) PART C (Day 1: 0 -5 hr), (Day 85: 0-5 hr)
Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time
Time frame: Baseline, Day 1, Day 85, Day 169
Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I).
Time frame: Baseline, Week 4, Week 24, Week 104
Number of Participants With Negative Anti-MCS110 Antibody
Time frame: Baseline, throughout the study up to Day 505
Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion
Time frame: Week 4
Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion
Time frame: Week 24/28, Week 104
Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS)
Time frame: Baseline, Week 4, Week 12, Week 24, Week 28, Week 40, Week 48, Week 104
Time to Relapse
Time frame: Up to Week 104
Time to Surgery
Time frame: Up to Week 104
Average of Health-Related Quality of Life Questionnaire Score for mHAQ
Time frame: up to 104 weeks
Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes
Time frame: Baseline Up to Week 104
Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
Time frame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
Time frame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
Time frame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
Time frame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
Time frame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire
Time frame: Week 4, Week 24, up to 104 weeks

Results and safety

Results posted to the registry on 27 Feb 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MCS110 10 mg/kg (PART A)	5	5
Placebo (PART A)	2	2
MCS110 10 mg/kg (PART B)	8	7
Placebo/10mg/kg (PART B)	3	3
MCS110 3 mg/kg (Part C)	3	0
MCS110 5 mg/kg (Part C)	3	3
MCS110 10 mg/kg (Part C)	4	3
MCS110 3 mg/kg & MCS110 10mg/kg (Part C)	4	4
MCS110 5 mg/kg & MCS110 10mg/kg (PART C)	4	3

Primary outcome: Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size

Time frame: Week 4. Mean (Standard Deviation). Unit: mm3

Measure	Placebo (PART ABC4) n = 5	MCS110 3 mg/kg (PART ABC4) n = 7	MCS110 5 mg/kg (PART ABC4) n = 7	MCS110 10 mg/kg (PART ABC4) n = 17
Value	-4222.8 (6284.56)	-668.5 (18751.44)	-9998.4 (15628.40)	-38002.1 (57314.73)

Population analysed: Pharmacodynamic Analysis Set

Primary outcome: Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size

Time frame: Week 4. Mean (Standard Deviation). Unit: Percentage

Measure	Placebo (PART ABC4) n = 5	MCS110 3 mg/kg (PART ABC4) n = 7	MCS110 5 mg/kg (PART ABC4) n = 7	MCS110 10 mg/kg (PART ABC4) n = 17
Value	-7.7 (5.10)	-7.4 (13.21)	-24.8 (23.42)	-32.6 (16.61)

Placebo (PART ABC4) vs MCS110 3 mg/kg (PART ABC4): Mean Difference (Net): 0.98 (95% CI 0.71 to 1.36), p = 0.915, ANCOVA
Placebo (PART ABC4) vs MCS110 5 mg/kg (PART ABC4): Median Difference (Net): 0.78 (95% CI 0.57 to 1.07), p = 0.117, ANCOVA
Placebo (PART ABC4) vs MCS110 10 mg/kg (PART ABC4): Mean Difference (Net): 0.69 (95% CI 0.52 to 0.91), p = 0.010, ANCOVA

Population analysed: Pharmacodynamic Analysis Set

Primary outcome: Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size

Time frame: Up to 8 weeks post last dose. Mean (Standard Deviation). Unit: mm3

Measure	MCS110 3 mg/kg (PART C) n = 7	MCS110 5 mg/kg (PART C) n = 7	MCS110 10 mg/kg (PART BC) n = 15	MCS110 3 mg/kg & MCS110 10mg/kg (Part C) n = 4	MCS110 5 mg/kg & MCS110 10mg/kg (Part C) n = 4
Value	-2450.3 (2721.24)	-29164.3 (23286.18)	-37015.1 (29297.02)	-42420.1 (63812.69)	-3571.9 (3612.97)

Population analysed: Pharmacodynamic Analysis Set

Primary outcome: Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size

Time frame: Up to 8 weeks post last dose. Mean (Standard Deviation). Unit: Percentage

Measure	MCS110 3 mg/kg (PART BC) n = 7	MCS110 5 mg/kg (PART BC) n = 7	MCS110 10 mg/kg (PART BC) n = 15	MCS110 3 mg/kg & MCS110 10mg/kg (Part BC) n = 4	MCS110 5 mg/kg & MCS110 10mg/kg (Part BC) n = 4
Value	-29.7 (33.73)	-56.3 (20.31)	-55.0 (19.02)	-45.8 (40.11)	-22.6 (16.21)

Population analysed: Pharmacodynamic Analysis Set

19 secondary outcomes are reported in the full results.

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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MCS110 10 mg/kg (PART A)	0 of 5 (0%)	3 of 5 (60%)	0 of 5
Placebo (PART A)	1 of 2 (50%)	1 of 2 (50%)	0 of 2
MCS110 10mg/kg (PART B)	2 of 11 (18.2%)	11 of 11 (100%)	0 of 11
Placebo/10mg/kg (PART B)	0 of 3 (0%)	3 of 3 (100%)	0 of 3
MCS110 3mg/kg (PART C)	3 of 7 (42.9%)	7 of 7 (100%)	0 of 7
MCS110 5mg/kg (PART C)	1 of 7 (14.3%)	6 of 7 (85.7%)	0 of 7
MCS110 10mg/kg (PART C)	4 of 12 (33.3%)	11 of 12 (91.7%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 18296418Blay JY, El Sayadi H, Thiesse P, Garret J, Ray-Coquard I. Complete response to imatinib in relapsing pigmented villonodular synovitis/tenosynovial giant cell tumor (PVNS/TGCT). Ann Oncol. 2008 Apr;19(4):821-2. doi: 10.1093/annonc/mdn033. Epub 2008 Feb 21. No abstract available.
Ann Oncol. 2008 Apr;19(4):821-2. Epub 2008 Feb 21; Complete response to imatinib in relapsing pigmented villonodular synovitis/tenosynovial giant cell tumor (PVNS/TGCT)Link provided by the sponsor.
A Plain Language Trial Summary is available on novartisclinicatrials.comLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

8 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MCS110 in people with Pigmented Villonodular Synovitis and PVNS, run by Novartis Pharmaceuticals at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size (time frame: Week 4). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01643850, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2021.