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MCS110 in Patients With Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01643850
First received: March 8, 2012
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

This study, designed as a proof of concept study of MCS110 in pigmented villonodular synovitis, will assess the clinical response to MCS110 treatment in Pigmented Villonodular Synovitis (PVNS) and Giant cell tumor of the tendon sheath (GCTTS) patients after multiple intravenous doses of MCS110 using magnetic resonance imaging to assess tumor volume, and to evaluate pharmacokinetics/pharmacodynamics, safety and tolerability in this population.


Condition Intervention Phase
Pigmented Villonodular Synovitis
PVNS
Giant Cell Tumor of the Tendon Sheath
GCCTS
Tenosynovial Giant Cell Tumor (Localized or Diffused Type)
Drug: MCS110
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Double -Blind, Placebo Controlled Study Followed by Open Label Dosing to Assess Safety, Tolerability and Effect on Tumor Size of MCS110 in Patients With Pigmented Villonodular Synovitis (PVNS)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCTTS) tumor size [ Time Frame: 8 weeks post last dose ] [ Designated as safety issue: No ]
    Primary endpoint is assessment of efficacy of multiple i.v. doses of MCS110 in reducing the volume of PVNS or GCTTS tumors evaluated by MRI after 8 weeks post last dose.

  • Number of participants with adverse events [ Time Frame: 8 weeks post last dose. ] [ Designated as safety issue: Yes ]
    Primary endpoint is assessment of safety and tolerability of multiple i.v. doses of MCS110 in this population.


Secondary Outcome Measures:
  • Pharmacokinetics of MCS110 and best estimates for key PK parameters including [not limited to] area under the serum concentration-time curve (AUC), clearance (CL), apparent volume of distribution (V), mean residence time (MRT), half-lives (T1/2), etc [ Time Frame: up to 96 weeks or up to 100 weeks ] [ Designated as safety issue: No ]
    Pharmacokinetic characterization of multiple doses of MCS110

  • Evaluation of macrophage-colony stimulating factor (MCSF) plasma concentrations over time [ Time Frame: up to 96 weeks or up to 100 weeks ] [ Designated as safety issue: No ]
    Pharmacodynamic characterization of multiple doses of MCS110

  • Change in Serum C-terminal Type 1 collagen peptide concentrations [ Time Frame: up to 96 weeks or up to 100 weeks ] [ Designated as safety issue: No ]
    Pharmacodynamic characterization of multiple doses of MCS110

  • Number of CD14+ CD16+ monocytes [ Time Frame: up to 96 weeks or up to 100 weeks ] [ Designated as safety issue: Yes ]
    Pharmacodynamic characterization of multiple doses of MCS110

  • Change in Joint range of motion score [ Time Frame: up to 96 weeks or up to 100 weeks ] [ Designated as safety issue: No ]
    Assessment of the duration of the clinical response

  • Change in EQ5D, mHAQ and joint specific questionnaires score [ Time Frame: up to 96 weeks or up to 100 weeks ] [ Designated as safety issue: No ]
    Assessment of the degree of functional recovery

  • Change in serum anti-MCS110 antibody concentrations [ Time Frame: up to 96 weeks or up to 100 weeks ] [ Designated as safety issue: Yes ]
    Assessment of the immunogenicity

  • Change of joint pain using a visual analog scale (VAS) [ Time Frame: up to 96 weeks or up to 100 weeks ] [ Designated as safety issue: No ]
    Assessment of joint pain

  • Time to surgery [ Time Frame: up to 96 weeks or up to 100 weeks ] [ Designated as safety issue: No ]
    Assessment time to surgery

  • Time to relapse [ Time Frame: up to 96 weeks or up to 100 weeks ] [ Designated as safety issue: No ]
    Assessment time to relapse based on MRI.


Estimated Enrollment: 18
Study Start Date: April 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MCS110
In the multiple dose Part B patients receive up to 4 doses of 10 mg/kg MCS110 administered i.v. once every 4 weeks starting at Day 1.
Drug: MCS110
Patients will receive up to 4 doses of MCS110 (10mg/kg) administered intravenously once every 4 weeks. Before each dosing, safety will be assessed.
Placebo Comparator: Placebo
Placebo infusion administered i.v. at Day 1 followed by up to 4 doses of MCS110 (10 mg/kg).
Drug: Placebo
Participants will receive a single dose of NaCl on day 1

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Patients with PVNS or GCTTS with, at least, one measurable site of disease on MRI.
  • 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 PVNS or GCTTS whose tumor is not evaluable by MRI, in the judgment of the central MRI reading site.
  • 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.
  • Evidence of liver disease or liver injury as indicated by abnormal liver function tests such as SGOT (AST), SGPT (ALT), gamma GT, alkaline phosphatase, or serum bilirubin.
  • 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.

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01643850

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, California
Novartis Investigative Site Recruiting
San Diego, California, United States, 92103-8894
United States, Colorado
Novartis Investigative Site Not yet recruiting
Denver, Colorado, United States, 80237
United States, District of Columbia
Novartis Investigative Site Recruiting
Washington, District of Columbia, United States, 20011
United States, Florida
Novartis Investigative Site Recruiting
Miami, Florida, United States, 33136
United States, Illinois
Novartis Investigative Site Recruiting
Chicago, Illinois, United States, 60612
United States, Minnesota
Novartis Investigative Site Recruiting
Minneapolis, Minnesota, United States, 55455
United States, Pennsylvania
Novartis Investigative Site Recruiting
Philadelphia, Pennsylvania, United States, 19107
Novartis Investigative Site Withdrawn
Pittsburgh, Pennsylvania, United States, 15219
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01643850     History of Changes
Other Study ID Numbers: CMCS110X2201, 2011-002951-32
Study First Received: March 8, 2012
Last Updated: September 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Pigmented Villonodular Synovitis
PVNS
Giant cell tumor of the tendon sheath
GCCTS
Tenosynovial giant cell tumor (localized or diffused type)
MCS110

Additional relevant MeSH terms:
Giant Cell Tumors
Neoplasms
Synovitis
Synovitis, Pigmented Villonodular
Joint Diseases
Musculoskeletal Diseases
Neoplasms by Histologic Type
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue

ClinicalTrials.gov processed this record on November 25, 2014