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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 May 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01643850
First received: March 8, 2012
Last updated: May 3, 2017
Last verified: May 2017
  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 GCTS Drug: MCS110 Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Double-blind (Part A, B and C), Placebo Controlled (Part A and B Only), Study to Assess Safety, Tolerability and Efficacy of MCS110 on Tumor Size in Patients With Pigmented Villonodular Synovitis (PVNS)

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

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 ]
    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. ]
    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 104 weeks ]
    Pharmacokinetic characterization of multiple doses of MCS110

  • Evaluation of macrophage-colony stimulating factor (MCSF) plasma concentrations over time [ Time Frame: up to 104 weeks ]
    Pharmacodynamic characterization of multiple doses of MCS110

  • Change in Serum C-terminal Type 1 collagen peptide concentrations [ Time Frame: up to 104 weeks ]
    Pharmacodynamic characterization of multiple doses of MCS110

  • Change in Joint range of motion score [ Time Frame: up to 104 weeks ]
    Assessment of the duration of the clinical response

  • Change in EQ5D, mHAQ and joint specific questionnaires score [ Time Frame: up to 104 weeks ]
    Assessment of the degree of functional recovery

  • Change in serum anti-MCS110 antibody concentrations [ Time Frame: up to 104 weeks ]
    Assessment of the immunogenicity

  • Change of joint pain using a visual analog scale (VAS) [ Time Frame: up to 104 weeks ]
    Assessment of joint pain

  • Time to surgery [ Time Frame: up to 104 weeks ]
    Assessment time to surgery

  • Time to relapse [ Time Frame: up to 104 weeks ]
    Assessment time to relapse based on MRI.


Estimated Enrollment: 39
Actual Study Start Date: April 23, 2012
Estimated Study Completion Date: September 26, 2019
Estimated Primary Completion Date: September 26, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MCS110

In the single dose Part A of the study, patients receive 1 dose of of 10 mg/kg MCS110 administered i.v. on Day 1.

In the multiple dose Part B patients receive up to 6 doses of 10 mg/kg MCS110 administered i.v. once every 4 weeks starting at Day 1, or at Day 29 if the first dose received was placebo.

In the multiple dose Part C patients receive up to 6 doses of 3 mg/kg or 5 mg/kg or 10 mg/kg MCS110 administered i.v. once every 4 weeks starting at Day 1.

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 Name: Intravenous infusion of MCS110.
Placebo Comparator: Placebo

In the single dose Part A of the study patients were to receive 1 dose of placebo administered i.v. on Day 1.

In the multiple dose Part B, patients receive placebo infusion administered i.v. at Day 1 followed by up to 6 doses of MCS110 (10 mg/kg).

Drug: Placebo
Participants will receive a single dose of NaCl on day 1 through intravenous infusion.
Other Name: Intravenous infusion of placebo.

  Eligibility

Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Patients with PVNS or GCTTS with, at least, one measurable site of disease on MRI.
  • Adolescents (≥ 12, <18 years old) eligible for enrollment need to have (1) symptomatic disease for which surgical intervention is indicated and the surgical procedure itself would be associated with significant morbidity or (2) recurrent disease.
  • Written informed consent must be obtained before any assessment is performed. For adolescent patients, written informed consent is required from the legal representative and the adolescent must assent to participation.
  • 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.
  • Sexually active males must use a condom during intercourse while taking drug and for 84 days after stopping investigational medication and should not father a child in this period.

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 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.
  • Hemoglobin level below 11.5 g/dL at screening,
  • Donation or loss of 400 mL or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation. For patients ≥12 - <18 years old: loss of ≥ 10% of blood within eight (8) weeks prior to screening, or longer if required by local regulation.
  • 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.
  • History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or BUN and/or urea values, or abnormal urinary constituents (e.g., albuminuria).
  • Patients receiving immunosuppressive treatment as well as corticosteroids which cannot be discontinued at least 4 weeks before dosing.
  • Recent (within the last three [3] years) and/or recurrent history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated), or history of atopic allergy (asthma, urticaria, eczematous dermatitis).
  • 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.
  • Farm workers or patients who drink un-pasteurized milk.
  • 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 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
United States, California
Novartis Investigative Site Recruiting
San Diego, California, United States, 92103-8894
United States, Colorado
Novartis Investigative Site Recruiting
Denver, Colorado, United States, 80237
United States, District of Columbia
Novartis Investigative Site Recruiting
Washington, D.C., 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
Switzerland
Novartis Investigative Site Recruiting
Basel, Switzerland, 4056
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01643850     History of Changes
Other Study ID Numbers: CMCS110X2201
2011-002951-32 ( EudraCT Number )
Study First Received: March 8, 2012
Last Updated: May 3, 2017
Individual Participant Data  
Plan to Share IPD: Undecided
Plan Description:

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


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( 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
Synovitis
Synovitis, Pigmented Villonodular
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Joint Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on June 28, 2017