Phase 2
N=36
MCS110 in Patients With Pigmented Villonodular Synovitis (PVNS)
Pigmented Villonodular Synovitis · PVNS · Giant Cell Tumor of the Tendon Sheath · GCCTS · Tenosynovial Giant Cell Tumor Localized or Diffused Type
Bottom Line
View on ClinicalTrials.gov: NCT01643850 ↗Enrolled (actual)
36
Serious AEs
23.4%
Results posted
Feb 2020
Primary outcome: Primary: Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size — -4222.8; -668.5; -9998.4; -38002.1 mm3
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- MCS110 (Drug); Placebo (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Dec 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size |
-4222.8; -668.5; -9998.4; -38002.1 | — |
| PRIMARY Percent Change in Pigmented Villonodular Synovitis (PVNS) Tumor Size |
-7.7; -7.4; -24.8; -32.6 | 0.915 |
| PRIMARY Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size |
-2450.3; -29164.3; -37015.1; -42420.1; -3571.9 | — |
| PRIMARY Percentage Change in Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCTTS) Tumor Size |
-29.7; -56.3; -55.0; -45.8; -22.6 | — |
| PRIMARY Number of Participants With Adverse Events |
3; 1; 11; 1; 7; 6 | — |
| SECONDARY Pharmacokinetics of MCS110 Area Under the Serum Concentration-time Curve (AUC) |
75632187; 44258092; 12900096; 14559871; 44854588; 838099 | — |
| SECONDARY Pharmacokinetics of MCS110 Maximum Concentration (Cmax) |
234800; 206750; 66983; 85914; 214667; 194667 | — |
| SECONDARY Pharmacokinetics of MCS110 Total Maximum Concentration (Tmax) |
2.083; 1.192; 3.125; 5; 4; 1.467 | — |
| SECONDARY Change in Macrophage-colony Stimulating Factor (M-CSF) Plasma Concentrations Over Time |
4694.0; 4940.0; 5767.1; 5056.7; 4778.3; 5420.0 | — |
| SECONDARY Change in Serum C-terminal Type 1 Collagen Peptide Concentrations (CTX-I). |
0.3; 0.5; 0.4; 0.1; 0.6; 0.1 | — |
| SECONDARY Number of Participants With Negative Anti-MCS110 Antibody |
5; 1; 8; 3; 3; 3 | — |
| SECONDARY Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion |
-10.0; 0.0; -10.5; -26; 1; -2.0 | — |
| SECONDARY Assessment of Change From Baseline in Joint Range of Motion for Knee Extension and Flexion |
-10.0; 0.0; -10.5; -26; 1; -2.0 | — |
| SECONDARY Change From Baseline in Joint Pain Using a Visual Analog Scale (VAS) |
32; 9.3; 28.6; 39.3; 51.0; 22.5 | — |
| SECONDARY Time to Relapse |
337.0; 454.0; 477.0; 296.0; NA; NA | — |
| SECONDARY Time to Surgery |
387.0; 0; 0; 231.0; NA; NA | — |
| SECONDARY Average of Health-Related Quality of Life Questionnaire Score for mHAQ |
0.3; 0.1; 0.3; 0.3; 0.9; 0.1 | — |
| SECONDARY Number of CD14+ Monocytes and Number of CD14 + Monocytes and CD16+ Monocytes |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Change From Baseline Per Treatment for Activities of Daily Living (ADL) in the Knee Injury and Osteoarthritis Outcome Score (KOOS) |
65.4; 69.1; 77.3; 70.6; 71.3; 79.4 | — |
| SECONDARY Change From Baseline Per Treatment for Knee Related Quality of Life in the Knee Injury and Osteoarthritis Outcome Score (KOOS) |
15.6; 37.5; 29.5; 50.0; 40.6; 31.3 | — |
| SECONDARY Change From Baseline Per Treatment for Pain and Discomfort in the Knee Injury and Osteoarthritis Outcome Score (KOOS) |
54.2; 52.8; 62.6; 66.7; 61.1; 66.7 | — |
| SECONDARY Change From Baseline Per Treatment for Sport/Recreation in the Knee Injury and Osteoarthritis Outcome Score (KOOS) |
35.0; 25.0; 29.5; 70.0; 52.5; 50.0 | — |
| SECONDARY Change From Baseline Per Treatment for Symptoms in the Knee Injury and Osteoarthritis Outcome Score (KOOS) |
41.1; 50.0; 50.0; 50.0; 62.5; 58.9 | — |
| SECONDARY Change From Baseline Per Treatment Using EuroQol-5 Dimensional (EQ-5D VAS)Visual Analog Scale Quality of Life Questionnaire |
11.0; 3.7; 0.6; 1.3; 5.5; -1.0 | — |
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.
Data sourced from ClinicalTrials.gov (NCT01643850). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.