Clinical trial NCT05394116: A Study to Assess Safety, Tolerability and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP)
Official title: Phase 3 Randomized, Placebo-Controlled Study to Assess Safety, Tolerability, and Efficacy of Garetosmab in Patients With Fibrodysplasia Ossificans Progressiva
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Fibrodysplasia Ossificans Progressiva
Keywords: Heterotopic Ossification (HO) Lesions
Type I activin A receptor (ACVR1)
Optima
LUMINA-1
Flare-Ups
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-05-27
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is researching an experimental drug called garetosmab. The study is focused on adult patients with fibrodysplasia ossificans progressiva (FOP).

The aim of the study is to see how safe and effective the study drug is in patients with FOP.

The study is looking at several other research questions, including:

* What side effects may happen from receiving the study drug
* How much study drug is in the blood at different times
* Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)


Eligibility criteria: Key Inclusion Criteria:

1. Clinical diagnosis of Fibrodysplasia Ossificans Progressiva (FOP) \[(based on findings of congenital malformation of the great toes, episodic soft tissue swelling, and/or progressive Heterotopic Ossification (HO)\]
2. Confirmation of FOP diagnosis with documentation of Type I activin A receptor (ACVR1) FOP causing mutation
3. FOP disease activity within 1 year of screening visit. FOP disease activity is defined as pain, swelling, stiffness, or other signs and symptoms associated with FOP flare-ups; or worsening of joint function, or radiographic progression of HO lesions (increase in size or number of HO lesions) with/without being associated with flare-up episodes
4. Willing and able to undergo CT imaging procedures and other procedures as defined in the protocol

Key Exclusion Criteria:

1. Cumulative Analog Joint Involvement Scale (CAJIS) score at screening \>19
2. Participant has significant concomitant illness or history of significant illness such as but not limited to cardiac, renal, rheumatologic, neurologic, psychiatric, endocrine, metabolic, or lymphatic disease, that in the opinion of the study investigator might confound the results of the study or pose additional risk to the patient by their participation in the study
3. Previous history or diagnosis of cancer
4. Severely impaired renal function defined as estimated glomerular filtration rate \<30 milliliter per minute (mL/min) (/1.73 m\^2 calculated by the Modification of Diet in Renal Disease equation
5. Uncontrolled diabetes defined as hemoglobin A1C (HbA1c) \>9% at screening
6. History of poorly controlled hypertension, as defined by:

   1. Systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥110 mm Hg at the screening visit
   2. Systolic blood pressure of 160 mm Hg to 179 mm Hg or diastolic blood pressure of 100 mm Hg to 10\^9 mm Hg at the screening visit, AND a history of end-organ damage (including history of left-ventricular hypertrophy, heart failure, angina, myocardial infarction, stroke, transient ischemic attack, peripheral arterial disease, end-stage renal disease, and moderate-to-advanced retinopathy
7. Known history of cerebral vascular malformation
8. Cardiovascular conditions such as New York Heart Association class III or IV heart failure, cardiomyopathy, intermittent claudication, myocardial infarction, or acute coronary syndrome within 6 months prior to screening; symptomatic ventricular cardiac arrhythmia
9. History of severe respiratory compromise requiring oxygen, respiratory support (eg, bilevel positive airway pressure \[biPAP\] or continuous positive airway pressure \[CPAP\]), or a history of aspiration pneumonia requiring hospitalization
10. Prior use in the past year and concomitant use of bisphosphonates
11. Concurrent participation in another interventional clinical study or a non-interventional study with radiographic measures or invasive procedures (eg, collection of blood or tissue samples)
12. Treatment with another investigational drug, denosumab, imatinib or isotretinoin in the last 30 days or within 5 half-lives of the investigational drug, whichever is longer
13. Pregnant or breastfeeding women
14. Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception, as defined in the protocol
15. Male patients with WOCBP partners who are not willing to use condoms with WOCBP partners to prevent potential fetal exposure, as defined in the protocol

Note: Other protocol defined Inclusion/Exclusion Criteria apply

Primary outcomes:
measure: Number of new HO lesions
timeFrame: At Week 56
measure: Incidence and severity of treatment-emergent adverse events of special interest (AESIs)
timeFrame: Baseline to Week 56
Secondary outcomes:
measure: Number of clinician-assessed flare-ups
timeFrame: Through Weeks 28, 56 and 84
measure: Occurrence of new HO lesions
timeFrame: At Weeks 28, 56 and 84
measure: Total volume of new HO lesions
timeFrame: At Weeks 28, 56 and 84
measure: Occurrence of patient-reported flare-ups
timeFrame: Through Weeks 28 and 56
measure: Number of new HO lesions
timeFrame: At week 28 and 84
measure: Occurrence of clinician-assessed flare-ups
timeFrame: Through Weeks 28, 56 and 84
measure: Number of patient-reported flare-ups
timeFrame: Through Weeks 28 and 56
measure: Change in joint function assessment by physician using cumulative analog joint involvement scale (CAJIS)
timeFrame: Baseline to Weeks 28 and 56
measure: Change in pulmonary function as assessed by spirometry
timeFrame: Baseline at Weeks 28 and 56
measure: Change in disease severity as assessed by the Patient Global Impression of Severity (PGIS)
timeFrame: Baseline to Weeks 28 and 56
measure: Change in disease severity as assessed by the Patient's Global Impression of Change (PGIC)
timeFrame: At Weeks 28 and 56
measure: Change in disease severity as assessed by the Clinician's Global Impression of Change (CGIC)
timeFrame: At Weeks 28 and 56
measure: Concentration of total activin A in serum over time
timeFrame: Through Week 56
measure: Concentration of garetosmab in serum over time
timeFrame: Through Week 56
measure: Incidence of anti-drug antibodies (ADA) to garetosmab over time
timeFrame: Through Week 56
measure: Titer of ADA to garetosmab over time
timeFrame: Through Week 56
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA) Medical Center
state: California
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sao Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: Concepcion
country: Chile
facility: Universidad de Concepcion
state: Bio Bio
city: Shanghai
country: China
facility: Tongji Hospital of Tongji University
city: Chia
country: Colombia
facility: Clinica Universidad de La Sabana
state: Cundinamarca
city: Helsinki
country: Finland
facility: HUS Children and Adolescents Park Hospital Clinical Trial Unit
state: Stenbäckinkatu 11
city: Montpellier
country: France
facility: Hôpital Lapeyronie
city: Paris
country: France
facility: Hopital Lariboisiere
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Genoa
country: Italy
facility: IRCCS Istituto Giannina Gaslini
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Yufu
country: Japan
facility: Oita University Hospital
state: Oita
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lampur
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center
state: North Holland
city: Rzeszow
country: Poland
facility: Szpital Centrum Medyczne Medyk
state: Podkarpackie
city: Rondebosch
country: South Africa
facility: University of Cape Town
state: Cape Town
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Middlesex
country: United Kingdom
facility: Royal National Orthropaedic Hospital NHS Trust
state: Greater London
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: