The Examination of Safety and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP)

JRCT ID: jRCT2041220096

Registered date:25/11/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Fibrodysplasia Ossificans Progressiva
• Date of first enrollment: 18/01/2023
• Target sample size: 6
• Countries of recruitment: Australia,Japan,Canada,Japan,Chile,Japan,Finland,Japan,France,Japan,Hong Kong,Japan,Malaysia,Japan,Netherlands,Japan,Colombia,Japan,Mexico,Japan,Poland,Japan,Korea,Japan,United Kingdom,Japan,United States,Japan,Brazil,Japan,China,Japan,Italy,Japan,South Africa,Japan,Spain,Japan
• Study type: Interventional

Intervention(s)

- Drug: Garetosmab. Garetosmab is supplied as a liquid drug product and will be administered IV. Other Name: R2477
[High dose Garetosmab] Garetosmab is administered by intravenous (IV) administration every 4 weeks (Q4W)
[Low dose Garetosmab] Garetosmab is administered by IV administration Q4W
-Drug: Placebo. Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV.

Outcome(s)

Primary Outcome

1. Number of new HO lesions adjudicated as positive based on CT [ Time Frame: Through week 56]
2. Incidence and severity of treatment-emergent adverse events of special interest (AESIs) [ Time Frame: Baseline to Week 56]

Secondary Outcome

1. Number of clinician-assessed flare-ups [ Time Frame: Through Week 28 and 56]
2. Occurrence of clinician-assessed flare-ups [ Time Frame: Through Weeks 28 and 56]: Reported as Yes/No
3. Number of patient-reported flare-ups [ Time Frame: Through Weeks 28 and 56]
4. Occurrence of patient-reported flare-ups [ Time Frame: Through Weeks 28 and 56] :Reported as Yes/No
5. Occurrence of new HO lesions adjudicated as positive based on CT [ Time Frame: Weeks 28 and 56]: Reported as Yes/No
6. Total volume of new HO lesions adjudicated as positive based on CT [ Time Frame: Weeks 28 and 56]
7. Number of new HO lesions adjudicated as positive based on CT [ Time Frame: Week 28]
8. Change in joint function assessment by physician using cumulative analog joint involvement scale (CAJIS) [ Time Frame: Baseline to Week 28 and 56]
9. Change in pulmonary function as assessed by spirometry [ Time Frame: Baseline to Week 28 and 56]
10. Change in disease severity as assessed by the Patient Global Impression of Severity (PGIS) [ Time Frame: Baseline to Week 28 and 56]
11. Change in disease severity as assessed by the Patient's Global Impression of Change (PGIC) [ Time Frame: Baseline to Week 28 and 56]
12. Change in disease severity as assessed by the Clinician's Global Impression of Change (CGIC) [Time Frame: Baseline to Week 28 and 56]
13. Concentration of total activin A in serum over time [ Time Frame: Baseline to Week 56]
14. Concentrations of garetosmab in serum [Time Frame: Baseline to Week 56]
15. Incidence of anti-drug antibodies (ADA) to garetosmab [Time Frame: Baseline to Week 56]
16. Titer of ADA to garetosmab [Time Frame: Baseline to Week 56]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Male or female 18 years or older at screening
2. 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)]
3. Confirmation of FOP diagnosis with documentation of Type I activin A receptor (ACVR1) FOP causing mutation
4. 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
5. Willing and able to undergo CT imaging procedures and other procedures as defined in the protocol
6. Other Protocol Defined Inclusion Criteria Apply

Exclude 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:
a. Systolic blood pressure >=180 mm Hg or diastolic blood pressure >=110 mm Hg at the screening visit
b. Systolic blood pressure of 160 mm Hg to 179 mm Hg or diastolic blood pressure of 100 mm Hg to 109 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
15. Male patients with WOCBP partners who are not willing to use condoms with WOCBP partners to prevent potential fetal exposure
16. Other Protocol Defined Exclusion Criteria Apply

Related Information

• Primary Sponsor: Rhee Susan
• Secondary ID(s): NCT05394116,2022-000880-40