MCS110 in Patients With Pigmented Villonodular Synovitis (PVNS)

NCT01643850 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CMCS110X22012011-002951-32
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 8

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.

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

Outcome Measures

Primary Outcomes (5)

• 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".

  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".

  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 \[5/10 mg/kg\]

  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 \[5/10 mg/kg\].

  Up to 8 weeks post last dose

• Number of Participants With Adverse Events

  Overall incidence of Adverse Events

  Approximately 2 years

Secondary Outcomes (19)

• 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)

• 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)

• 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)

• Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time

  Baseline, Day 1, Day 85, Day 169

• Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I).

  Baseline, Week 4, Week 24, Week 104

Study Arms (7)

MCS110

EXPERIMENTAL

Participants will receive a single dose of 10mg/kg on day 1 administered by regular infusion.

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)

Drug: Placebo

MCS110 3 mg/kg

EXPERIMENTAL

Part C: MCS110 3 mg/kg (i.v. infusion)

Drug: MCS110

MCS110 5 mg/kg

EXPERIMENTAL

Part C: MCS110 5 mg/kg (i.v. infusion)

Drug: MCS110

MCS110 10 mg/kg

EXPERIMENTAL

Part C: MCS110 10 mg/kg (i.v. infusion)

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)

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)

Drug: MCS110

Interventions

MCS110 DRUG

Patients will receive up to 6 doses of MCS110 (3 or 5 or 10mg/kg) administered intravenously once every 4 weeks. Before each dosing, safety will be assessed.

Also known as: Intravenous infusion of MCS110.

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

Placebo DRUG

Participants will receive a single dose of NaCl on day 1 through intravenous infusion.

Also known as: Intravenous infusion of placebo.

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Novartis Investigative Site

San Diego, California, 92103-8894, United States

Location

Novartis Investigative Site

Denver, Colorado, 80237, United States

Location

Novartis Investigative Site

Washington D.C., District of Columbia, 20011, United States

Location

Novartis Investigative Site

Miami, Florida, 33136, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60612, United States

Location

Novartis Investigative Site

Minneapolis, Minnesota, 55455, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19107, United States

Location

Novartis Investigative Site

Basel, 4056, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 18296418 BACKGROUND

Related Links

• 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)
• A Plain Language Trial Summary is available on novartisclinicatrials.com

MeSH Terms

Conditions

Synovitis, Pigmented Villonodular; Giant Cell Tumor of Tendon Sheath

Condition Hierarchy (Ancestors)

Giant Cell Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Synovitis; Joint Diseases; Musculoskeletal Diseases; Tendinopathy; Muscular Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2012
• First Posted: July 18, 2012
• Study Start: April 23, 2012
• Primary Completion: December 7, 2017
• Study Completion: December 21, 2018
• Last Updated: January 5, 2021
• Results First Posted: February 27, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share

Locations

US (7); CH (1)