MCS110 in Patients With Pigmented Villonodular Synovitis (PVNS)

Novartis

Status and phase: Completed; Phase 2

Conditions: Giant Cell Tumor of the Tendon Sheath; GCTS; GCCTS; Pigmented Villonodular Synovitis; Tenosynovial Giant Cell Tumor Localized or Diffused Type; PVNS

Treatments: Drug: Placebo; Drug: MCS110

Study type: Interventional

Funder types: Industry

Identifiers

NCT01643850

CMCS110X2201

2011-002951-32 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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36 participants in 7 patient groups, including a placebo group

MCS110

Experimental group

Description:

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

Treatment:

Drug: MCS110

Placebo

Placebo Comparator group

Description:

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)

Treatment:

Drug: Placebo

MCS110 3 mg/kg

Experimental group

Description:

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

Treatment:

Drug: MCS110

MCS110 5 mg/kg

Experimental group

Description:

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

Treatment:

Drug: MCS110

MCS110 10 mg/kg

Experimental group

Description:

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

Treatment:

Drug: MCS110

MCS110 3 mg/kg & MCS110 10mg/kg

Experimental group

Description:

Part C: MCS110 3 mg/kg (i.v. infusion) \& MCS110 10 mg/kg (i.v. infusion)

Treatment:

Drug: MCS110

MCS110 5 mg/kg & MCS110 10mg/kg

Experimental group

Description:

Part C: MCS110 5 mg/kg (i.v. infusion) \& MCS110 10 mg/kg (i.v. infusion)

Treatment:

Drug: MCS110