A Study to Assess Safety, Tolerability and Efficacy of Garetosmab versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP) (OPTIMA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

2 Mar 2023 → ongoing

Decision date (initial)

2024-05-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2023-508350-26-00

EudraCT number

2022-000880-40

ClinicalTrials.gov

NCT05394116

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary efficacy objective of the study is to assess the effect of garetosmab versus placebo on the formation of new HO lesions, as determined by low-dose computerized tomography (CT).
The primary safety objective of the study is to assess the safety and tolerability of garetosmab versus placebo.

Secondary objectives 5

1. To assess the effect of garetosmab versus placebo on the number per patient of clinician-assessed flare-up episodes.
2. To assess the effect of garetosmab versus placebo on the proportion of patients with new HO lesions as determined by CT.
3. To assess the effect of garetosmab versus placebo on volume of new HO lesions as determined by CT.
4. To assess the effect of garetosmab versus placebo on the occurrence of patient-reported flare-up episodes.
5. To assess the long term safety and efficacy of garetosmab.

Conditions and MedDRA coding

Fibrodysplasia Ossificans Progressiva

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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.
5. Note: Other protocol defined Inclusion Criteria apply

Exclusion criteria 16

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, 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.
16. Note: Other protocol defined Exclusion Criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Number of new HO lesions
2. Incidence and severity of treatment-emergent adverse events of special interest (AESIs)

Secondary endpoints 16

1. Number of clinician-assessed flare-ups.
2. Occurrence of new HO lesions
3. Total volume of new HO lesions
4. Occurrence of patient-reported flare-ups
5. Number of new HO lesions
6. Occurrence of clinician-assessed flare ups
7. Number of patient reported flare-ups
8. Change in joint function assessment by physician using cumulative analog joint involvement scale (CAJIS)
9. Change in pulmonary function as assessed by spirometry
10. Change in disease severity as assessed by the Patient Global Impression of Severity (PGIS)
11. Change in disease severity as assessed by the Patient’s Global Impression of Change (PGIC).
12. Change in disease severity as assessed by the Clinician’s Global Impression of Change (CGIC).
13. Concentration of total activin A in serum over time.
14. Concentrations of garetosmab in serum over time.
15. Incidence of anti-drug antibodies (ADA) to garetosmab over time.
16. Titer of ADA to garetosmab over time.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Third parties 14

Locations

6 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications