Evaluation of Pamrevlumab for the Treatment of Ambulatory Patients Affected by Duchenne Muscular Dystrophy and just Treated with Corticosteroids

• Register: EUCTR
• Last refreshed on: 30 August 2021
• Main ID: EUCTR2020-000699-39-IT
• Date of registration: 04/06/2021
• Prospective Registration: No
• Primary sponsor: FIBROGEN
• Public title: Evaluation of Pamrevlumab for the Treatment of Ambulatory Patients Affected by Duchenne Muscular Dystrophy and just Treated with Corticosteroids
• Scientific title: A Phase 3, Randomized, Double-Blind, Trial of Pamrevlumab (FG-3019) or Placebo in Combination with Systemic Corticosteroids in Ambulatory Subjects with Duchenne Muscular Dystrophy (DMD) - na
• Date of first enrolment: 19/04/2021
• Target sample size: 70
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-000699-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: open label extension If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, Czechia, France, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: FibroGen, Inc.

• Name: Clinical Trials Information
• Affiliation: FibroGen, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Double-blind phase:
Age and Consent
1. Males at least 6 to < 12 years of age at screening initiation;
2. Written consent by legal guardian as per regional/ country and/or IRB/IEC requirements;

DMD Diagnosis:
3. Medical history includes diagnosis of DMD and confirmed Duchenne mutation using a validated genetic test.

Pulmonary Criteria:
4. Average (of Screening and Day 0) percent predicted FVC above 45%;
5. On a stable dose of systemic corticosteroids for a minimum of 6 months, with no substantial change in dosage for a minimum of 3 months (except for adjustments for changes in body weight) prior to screening. Corticosteroid dosage should be in compliance with the DMD Care Considerations Working Group recommendations (e.g. prednisone or prednisolone 0.75 mg/kg per day or deflazacort 0.9 mg/kg per day) orstable dose. A reasonable expectation is that dosage and dosing regimen would not change significantly for the duration of the study.

Performance Criteria:
6. Able to complte 6MWD test with a distance of at least 270M but no more than 450M on two occasions within 3 months prior to Randomisation with <=10% variation between these two tests.
7. Able to rise (TTSTAND) from floor in <10 seconds (without aids/orthoses) at screening visit.
8. Able to undergo MRI test for the lower extremities vastus lateralis muscle.

Vaccination:
9. Received pneumococcal vaccine (PPSV23) (or any other pneumococcal polysaccharidevaccine as per national recommendations) and is receiving annual influenza vaccinations.

Laboratory Criteria:
10. Adequate renal function: cystatin C <=1.4 mg/L;
11. Adequate hematology and electrolytes parameters:
a. Platelets >100,000/mcL
b. Hemoglobin >12 g/dL
c. Absolute neutrophil count >1500 /µL
d. Serum calcium (Ca), potassium (K), sodium (Na), magnesium (Mg) and phosphorus(P) levels are within a clinically accepted range;
12. Adequate hepatic function:
a. No history or evidence of liver disease
b. Gamma glutamyl transferase (GGT) <=3x upper limit of normal (ULN)
c. Total bilirubin <=1.5xULN.

Open-label extension phase:
All patients must have completed treatment through the primary endpoint and completed the Week 52 visit on the double-blind phase. The study investigator must consider the subject medically stable for continued treatment. Written consent/assent by the patients and/or their legal guardian must be obtained prior to the patient’s participation in the open-label extension phase.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Both phases:
General criteria:
1. Concurrent illness other than DMD that can cause muscle weakness and/or impairment of motor function.
2. Severe intellectual impairment (eg. severe autism, sever cognitive impairment, severe behavioral disturbance) preventing the ability to perform study assessments in the investigator´s judgement.
3. Previous exposure to pamrevlumab.
4. BMI >=40 kg/m2 or weight >117 kg.
5. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies.
6. Exposure to any investigational drug (for DMD or not), in the 30 days prior to screening initiation or use of approved DMD therapies (e.g., eteplirsen, ataluren) within 5 half-lives of screening, whichever is longer, with the exception of the systemic corticosteroids, including deflazacort.

Cardiac and Pulmonary Criteria:
7. Requires >= 16 hours continuous ventilation.
8. Poorly controlled asthma or underlying lung disease such as bronchitis, bronchiectasis, emphysema, recurrent pneumonia that in the opinion of the investigator might impact respiratory function.
9. Hospitalization due to respiratory failure within 8 weeks prior to screening.
10. Severe uncontrolled heart failure (NYHA Classes III-IV), including any of the following:
a. Need for intravenous diuretics or inotropic support within 8 weeks prior to screening
b. Hospitalization for a heart failure exacerbation or arrhythmia within 8 weeks prior to screening.
11. Arrhythmia requiring anti-arrhythmic therapy.
12. Any other evidence of clinically significant structural or functional heart abnormality.

Clinical Judgments:
13. The Investigator judges that the subject will be unable to fully participate in the study and complete it for any reason, including inability to comply with study procedures and treatment, or any other relevant medical, surgical or psychiatric conditions.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Ambulatory Duchenne Muscular Dystrophy
MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: Pamrevlumab
Product Code: [FG-3019]
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PAMREVLUMAB
CAS Number: 946415-13-0
Current Sponsor code: FG-3019
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: Evaluation of the efficacy and safety of pamrevlumab versus placebo in combination with systemic corticosteroids administered every two weeks in ambulatory subjects with Duchenne muscular dystrophy (age 6 to 11 years).

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: Double-blind phase:
Change in NorthStar Ambulatory Assessment (NSAA) Linearized total score. Baseline, Week 52

Open label phase:
• Annual mean change in NorthStar Ambulatory Assessment (NSAA) Linerised total score;
• Annual mean change in 4-stair climb Velocity (4SCV) assessment;
• Annual mean change in the 10-meter walk/run test;
• Annual mean change in Time to Stand (TTSTAND);
• annual mean change of the time of Loss of Ambulation (LoA) assessment.

Primary end point(s): Double-blind phase:
Ambulatory functional assessment:
• Change in NorthStar Ambulatory Assessment (NSAA) Linearized total score

Open label phase:
• Annual mean change in NorthStar Ambulatory Assessment (NSAA) Linerized total score;
• Annual mean change in 4-stair climb Velocity (4SCV) assessment;
• Annual mean change in the 10-meter walk/run test;
• Annual mean change in Time to Stand (TTSTAND);
• annual mean change of the time of Loss of Ambulation (LoA) assessment.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Double-blind phase:
• Change in 4-stair climb Velocity (4SCV) assessment: Baseline, week 52
• Change in the 10-meter walk/run test: Baseline, week 52
• Change in Time to Stand (TTSTAND): Baseline, week 52
• Time to Loss of Ambulation (LoA): Baseline, week 52

Secondary end point(s): Double-blind phase:
• Change in 4-stair climb Velocity (4SCV) assessment;
• Change in the 10-meter walk/run test;
• Change in Time to Stand (TTSTAND);
• Time to Loss of Ambulation (LoA).

Secondary ID(s)

126630

FGCL-3019-094

2020-000699-39-BE

Source(s) of Monetary Support

FibroGen, Inc.

Ethics review

Status: Approved
Approval date: 28/01/2021
Contact: