Phase 2
N=40
An Efficacy and Safety Study of Palovarotene to Treat Preosseous Flare-ups in FOP Subjects
Fibrodysplasia Ossificans Progressiva
Bottom Line
View on ClinicalTrials.gov: NCT02190747 ↗Enrolled (actual)
40
Serious AEs
10.0%
Results posted
Jun 2020
Primary outcome: Primary: Percentage of Responders at Week 6 — 100; 88.9; 88.9 percentage of subjects — p=0.1664
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Palovarotene (Drug); Placebo (Drug)
- Age
- Pediatric, Adult, Older Adult · 6+ yrs
- Sex
- All
- Sponsor
- Clementia Pharmaceuticals Inc.
- Primary completion
- May 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Responders at Week 6 |
100; 88.9; 88.9 | 0.1664 |
| SECONDARY Percentage of Subjects With New HO at Weeks 6 and 12 |
15.0; 22.2; 30.0; 15.0; 44.4; 40.0 | 0.2335 |
| SECONDARY Change From Baseline in Amount (Area) of New HO Formed at the Flare-up Site at Weeks 6 and 12 |
0.00; 38.85; 75.89; 19.00; 71.22; 621.71 | 0.6984 |
| SECONDARY Percentage of Responders at Week 12 |
95.0; 88.9; 77.8 | 0.1503 |
| SECONDARY Change From Baseline in Bone Specific Alkaline Phosphatase at Weeks 2, 4, 6 and 12 |
-1.33; -3.18; 12.02; -1.41; 3.80; 7.53 | — |
| SECONDARY Change From Baseline in C-Reactive Protein at Weeks 2, 4, 6 and 12 |
8.62; 0.09; -1.59; 1.48; 23.26; 2.34 | — |
| SECONDARY Change From Baseline in C-Terminal Telopeptide at Weeks 2, 4, 6 and 12 |
-0.020; 0.118; 0.071; 0.015; 0.095; 0.188 | — |
| SECONDARY Change From Baseline in Procollagen Type 1 N-Terminal Propeptide at Weeks 2, 4, 6 and 12 |
53.022; 78.930; 42.058; 123.986; 117.476; 194.193 | — |
| SECONDARY Change From Baseline in Procollagen Type 1 C-Terminal Propeptide Biomarker at Weeks 2, 4, 6 and 12 |
22.12; 23.26; 82.93; 72.16; 76.10; 140.26 | — |
| SECONDARY Change From Baseline in Amount of Bone Formation (Volume) at Weeks 6 and 12 |
2820.53; 326.58; 11459.42; 3857.95; 1184.99; 16181.64 | — |
| SECONDARY Percentage of Subjects With Soft Tissue Swelling and Cartilage Formation Assessed by Magnetic Resonance Imaging (MRI) or Ultrasound (US) at Weeks 6 and 12 |
50.0; 50.0; 66.7; 60.0; 66.7; 66.7 | — |
| SECONDARY Change From Baseline in Percent of Normal Arc of Motion at the Primary Joint (Flare-up Site) at Weeks 6 and 12 |
-0.40; -1.36; -0.99; 0.58; -4.23; -2.31 | — |
| SECONDARY Subject and Investigator Global Assessment of Movement at Weeks 6 and 12 |
0; 1; 0; 1; 0; 0 | — |
| SECONDARY Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12 |
-2.5; 0.0; -2.0; -3.2; -1.3; -1.9 | — |
| SECONDARY Percentage of Subjects Who Used Any Assistive Devices and Adaptations for Daily Living at Weeks 6 and 12 |
85.0; 100.0; 100.0; 90.5; 100.0; 100.0 | — |
| SECONDARY Duration of Active Symptomatic Flare-up |
22.1; 44.1; 34.4 | — |
| SECONDARY Change From Baseline in Percentage of Worst Total Score for FOP-Specific Physical Function Questionnaire (FOP-PFQ) at Weeks 2, 4, 6, 9 and 12 |
0.95; 0.31; 2.11; 3.42; 2.67; 2.91 | — |
| SECONDARY Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12 |
2.76; 0.00; 5.90; 4.66; 2.66; 5.56 | — |
| SECONDARY Maximum Measured Plasma Concentration (Cmax) of Palovarotene |
95620.00; 35620.00; 45505.88; 18958.57 | — |
| SECONDARY Minimum Measured Plasma Concentration (Cmin) of Palovarotene |
3128.53; 1739.40; 3879.00; 614.14 | — |
| SECONDARY Time of Maximum Measured Plasma Concentration (Tmax) of Palovarotene |
3.00; 2.77; 3.00; 3.00 | — |
| SECONDARY Apparent Terminal Elimination Half-life (t1/2) of Palovarotene |
4.33; 5.18; 4.39; 4.40 | — |
| SECONDARY Area Under the Plasma Concentration Versus Time Curve Over the 24-hr Dosing Interval (AUC[0-24hr]) of Palovarotene |
686308.92; 350124.65; 311082.39; 142748.47 | — |
| SECONDARY Apparent Clearance of Palovarotene (CL/F) |
15.55; 12.84; 17.71; 19.51 | — |
Summary
Fibrodysplasia ossificans progressiva (FOP) is a rare, severely disabling disease characterized by painful, recurrent episodes of soft tissue swelling (flare-ups) that result in abnormal bone formation in muscles, tendons, and ligaments. Flare-ups begin early in life and may occur spontaneously or after soft tissue trauma, vaccinations, or influenza infections. Recurrent flare-ups progressively restrict movement by locking joints leading to cumulative loss of function and disability. Mouse models of FOP have demonstrated the ability of retinoic acid receptor (RAR) gamma agonists to prevent heterotopic ossification (HO) following injury. The purpose of the study is to evaluate whether palovarotene, an RAR gamma agonist, will prevent HO during and following a flare-up in subjects with FOP.
Eligibility Criteria
Inclusion Criteria
- Written, signed, and dated informed subject/parent consent or age-appropriate assent.
- Subjects clinically diagnosed with classic Fibrodysplasia Ossificans Progressiva (FOP).
- Symptomatic onset of a distinct flare-up within 7 days of Study Day 1 (start of study drug) and defined by the presence of at least two of six of the following symptoms: pain, soft tissue swelling, decreased range of motion, stiffness, redness, and warmth. Flare-up must be confirmed by the physician at the Screening visit.
- Flare-up is at an appendicular area (upper or lower extremity), abdomen, or chest; and subject has received, is receiving, or is willing to receive treatment per standard of care, which may or may not include oral prednisone (2 mg/kg PO to a maximum dose of 100 mg daily) for 4 days.
- Abstinent or using two highly effective forms of birth control.
- Subjects must be accessible for treatment and follow-up. Subjects living at distant locations from the investigational site must be able and willing to travel to a site for the initial and all follow-up visits.
Exclusion Criteria
- Weight 1.5x above the upper limit of normal or with a history of chronic pancreatitis.
- Elevated aspartate aminotransferase or alanine aminotransferase >2.5x the upper limit of normal.
- Fasting triglycerides >400 mg/dL with or without therapy.
Data sourced from ClinicalTrials.gov (NCT02190747). 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.