GARETOSMAB for Fibrodysplasia ossificans progressiva

Inclusion criteria

• {"criterion_text":"- 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)].\n- Confirmation of FOP diagnosis with documentation of Type I activin A receptor (ACVR1) FOP causing mutation.\n- 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.\n- Willing and able to undergo CT imaging procedures and other procedures as defined in the protocol.\n- Note: Other protocol defined Inclusion Criteria apply"}

Exclusion criteria

• {"criterion_text":"- Cumulative Analog Joint Involvement Scale (CAJIS) score at screening >19.\n- Prior use in the past year and concomitant use of bisphosphonates.\n- 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).\n- 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.\n- Pregnant or breastfeeding women.\n- Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception, as defined in the protocol.\n- 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.\n- Note: Other protocol defined Exclusion Criteria apply\n- 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.\n- Previous history or diagnosis of cancer.\n- 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.\n- Uncontrolled diabetes defined as hemoglobin A1C (HbA1c) >9% at screening.\n- 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.\n- Known history of cerebral vascular malformation.\n- 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.\n- 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."}

Primary endpoints

• {"endpoint_text":"- Number of new HO lesions","definition_or_measurement_approach":"Formation of new HO lesions as determined by low-dose computerized tomography (CT)."}
• {"endpoint_text":"- Incidence and severity of treatment-emergent adverse events of special interest (AESIs)","definition_or_measurement_approach":"Incidence and severity of treatment-emergent adverse events of special interest observed during treatment (safety/tolerability assessment)."}

Secondary endpoints

• {"endpoint_text":"- Number of clinician-assessed flare-ups.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Occurrence of new HO lesions","definition_or_measurement_approach":""}
• {"endpoint_text":"- Total volume of new HO lesions","definition_or_measurement_approach":"Volume of new HO lesions as determined by CT."}
• {"endpoint_text":"- Occurrence of patient-reported flare-ups","definition_or_measurement_approach":""}
• {"endpoint_text":"- Number of new HO lesions","definition_or_measurement_approach":""}
• {"endpoint_text":"- Occurrence of clinician-assessed flare ups","definition_or_measurement_approach":""}
• {"endpoint_text":"- Number of patient reported flare-ups","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change in joint function assessment by physician using cumulative analog joint involvement scale (CAJIS)","definition_or_measurement_approach":"Assessment using the cumulative analog joint involvement scale (CAJIS)."}
• {"endpoint_text":"- Change in pulmonary function as assessed by spirometry","definition_or_measurement_approach":"Measured by spirometry."}
• {"endpoint_text":"- Change in disease severity as assessed by the Patient Global Impression of Severity (PGIS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change in disease severity as assessed by the Patient’s Global Impression of Change (PGIC).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Change in disease severity as assessed by the Clinician’s Global Impression of Change (CGIC).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Concentration of total activin A in serum over time.","definition_or_measurement_approach":"Serum concentration measurements of total activin A over time."}
• {"endpoint_text":"- Concentrations of garetosmab in serum over time.","definition_or_measurement_approach":"Serum pharmacokinetic measurements of garetosmab over time."}
• {"endpoint_text":"- Incidence of anti-drug antibodies (ADA) to garetosmab over time.","definition_or_measurement_approach":"Assessment of anti-drug antibody incidence over time."}
• {"endpoint_text":"- Titer of ADA to garetosmab over time.","definition_or_measurement_approach":"Measurement of ADA titer over time."}

Methods

• Subject recruitment managed by Clariness GmbH (listed sponsor third party; Germany) for subject recruitment.
• Recruitment arrangements documents submitted (K1/K2 recruitment arrangement documents available in CTIS for member states).

France

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

15-05-2024

Processing Time Days

43

Number Of Sites

1

Number Of Participants

2

Finland

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

14-05-2024

Processing Time Days

42

Number Of Sites

1

Number Of Participants

2

Netherlands

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

21-05-2024

Processing Time Days

49

Number Of Sites

1

Number Of Participants

3

Italy

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

20-05-2024

Processing Time Days

48

Number Of Sites

1

Number Of Participants

13

Spain

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

13-05-2024

Processing Time Days

41

Number Of Sites

1

Number Of Participants

1

Poland

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

16-05-2024

Processing Time Days

44

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Regeneron Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

CRO

Name

ICON Clinical Research Limited Ireland Filial

Responsibilities

Imaging

Third parties

• {"country":"Germany","full_name":"eResearchTechnology GmbH","duties_or_roles":"Spirometry","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Signant Health Management Limited","duties_or_roles":"eCOA","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mlm Medical Labs LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Gray Consulting Inc.","duties_or_roles":"Travel Assistance","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"ICON Clinical Research Limited Ireland Filial","duties_or_roles":"Imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"Central Lab","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yourway Transport Inc.","duties_or_roles":"Clinical Supply","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"CRO","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Clariness GmbH","duties_or_roles":"Subject Recruitment","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Home Health","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"IDMC","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Translation","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mlm Medical Labs LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}