Clinical trial NCT01643850: MCS110 in Patients With Pigmented Villonodular Synovitis (PVNS)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-07-18
Enrollment: 36
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size
timeFrame: Week 4
measure: Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size
timeFrame: Week 4
measure: Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size
timeFrame: Up to 8 weeks post last dose
measure: Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size
timeFrame: Up to 8 weeks post last dose
measure: Number of Participants With Adverse Events
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC)
timeFrame: 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)
measure: Pharmacokinetics of MCS110 Maximum Concentration (Cmax)
timeFrame: 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)
measure: Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax)
timeFrame: 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)
measure: Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time
timeFrame: Baseline, Day 1, Day 85, Day 169
measure: Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I).
timeFrame: Baseline, Week 4, Week 24, Week 104
measure: Number of Participants With Negative Anti-MCS110 Antibody
timeFrame: Baseline, throughout the study up to Day 505
measure: Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion
timeFrame: Week 4
measure: Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion
timeFrame: Week 24/28, Week 104
measure: Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS)
timeFrame: Baseline, Week 4, Week 12, Week 24, Week 28, Week 40, Week 48, Week 104
measure: Time to Relapse
timeFrame: Up to Week 104
measure: Time to Surgery
timeFrame: Up to Week 104
measure: Average of Health-Related Quality of Life Questionnaire Score for mHAQ
timeFrame: up to 104 weeks
measure: Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes
timeFrame: Baseline Up to Week 104
measure: Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
measure: Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
measure: Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
measure: Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
measure: Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: Baseline, Week 4, Week 12, Week 24, Week 48, Week 40, Week 72, Week 104 (end of study)
measure: Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire
timeFrame: Week 4, Week 24, up to 104 weeks
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Novartis Investigative Site
state: California
city: Denver
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Washington
country: United States
facility: Novartis Investigative Site
state: District of Columbia
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Minneapolis
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Basel
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.