Clinical Trials Register

Summary
EudraCT Number:	2020-000698-26
Sponsor's Protocol Code Number:	FGCL-3019-093
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-08-17
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2020-000698-26

A.3

Full title of the trial

A Phase 3, Randomized, Double-Blind, Trial of Pamrevlumab (FG-3019) or Placebo in Combination with Systemic Corticosteroids in Subjects with Non-ambulatory Duchenne Muscular Dystrophy (DMD)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Evaluation of Pamrevlumab for the Treatment of Male Patients Affected by Non-ambulatory Duchenne Muscular Dystrophy and just Treated with Corticosteroids

A.4.1

Sponsor's protocol code number

FGCL-3019-093

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04371666

A.5.4

Other Identifiers

Name:

IND (US)

Number:

126630

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	FibroGen, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	FibroGen, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	FibroGen, Inc.
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	409 Illinois Street
B.5.3.2	Town/ city	San Francisco
B.5.3.3	Post code	94158
B.5.3.4	Country	United States
B.5.6	E-mail	FG3019_093@Fibrogen.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/19/2234
D.3 Description of the IMP
D.3.1	Product name	Pamrevlumab
D.3.2	Product code	FG-3019
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PAMREVLUMAB
D.3.9.1	CAS number	946415-13-0
D.3.9.2	Current sponsor code	FG-3019
D.3.9.4	EV Substance Code	SUB198085
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Non-ambulatory Duchenne Muscular Dystrophy

E.1.1.1

Medical condition in easily understood language

Duchenne Muscle Dystrophy

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10013801
E.1.2	Term	Duchenne muscular dystrophy
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluation of the efficacy and safety of pamrevlumab versus placebo in combination with systemic corticosteroids in subjects with Duchenne muscular dystrophy (non-ambulatory, age 12 years and older).

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Double-blind phase:
Age, Consent, and Contraception
1. Males at least 12 years of age, non-ambulatory at screening initiation;
2. Written consent by patient and/or legal guardian as per regional/ country and/or IRB/IEC requirements;
3. Male subjects with partners of childbearing potential must use contraception during the conduct of the study, and for 12 weeks after the last dose of study drug.

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

Performance criteria:
5. Brooke Score for Arms and Shoulders ≤5:
6. Able to undergo MRI test for the upper arm extremities (Biceps Brachii muscle) andcardiac muscle;
7. Able to perform spirometry.

Pulmonary and Cardiac criteria:
8. Average (of Screening and Day 0) percent predicted FVC between 45 and 85, inclusive;
9. Left ventricular ejection fraction ≥50% as determined by cardiac MRI at screening or within 3 months prior to randomization (Day 0);
10. If subjects have a history of cardiomyopathy, then subject must be on a stable dose for cardiomyopathy/ heart failure medications (e.g., angiotensin converting enzyme inhibitors, aldosterone receptors blockers, angiotensin-receptor blockers, and beta-blockers) for at least 1 month prior to screening. If subjects have no diagnosis of cardiomyopathy, then no dose of cardiomyopathy/heart failure medication is required for eligibility.
11. On a stable dose of systemic corticosteroids for a minimum of 6 months, with nos ubstantial 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.

Vaccination:
12. Agreement to receive annual influenza vaccinations during the course of the study.

Laboratory criteria:
13. Adequate renal function: cystatin C ≤1.4 mg/L;
14. 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 for DMD patients.
15. 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.

E.4

Principal exclusion criteria

Both phases:
General criteria:
1. Previous exposure to pamrevlumab;
2. BMI ≥40 kg/m2 or weight >117 kg;
3. History of:
a. allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies,
b. hypersensitivity to study drug or any component of study drug,
c. hypersensitivity reaction to Gadolinium-based Contrast Agents (GBCA) required for MRI acquisition;
4. 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 (exondys 51), ataluren, golodirsen (vyondys 53), casimersen (amondys 45)) within 5 half-lives of screening, whichever is longer, with the exception of the systemic corticosteroids,including deflazacort.

Cardiac, Renal and Pulmonary assessment:
5.Severe uncontrolled heart failure (NYHA Classes III-IV), or renal dysfunction, 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,
c. Patients with glomerular filtration rate (GFR) of less than 30 mL/min/1.73m2 or with other evidence of acute kidney injury as determined by investigator
6. Arrhythmia requiring anti-arrhythmic therapy;
7. Requires ≥16 hours continuous ventilation;
8. Hospitalization due to respiratory failure within the 8 weeks prior to screening;
9. 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.

Clinical judgments:
10.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 or psychiatric conditions which could confound efficacy assessment and/or safety assessment.

E.5 End points

E.5.1

Primary end point(s)

Double-blind phase:
Function assessment:
• Change in the total score of Performance of Upper Limb Version 2.0

Open-label extension phase:
Function assessment:
• Annual mean change in the total score of Performance of Upper Limb Version 2.0.
• Change in the subscores of three regional dimensions (High-level (shoulder), Midlevel (elbow), Distal-level (wrist and hand)) of PUL, from baseline to Week 52

Both phases:
Safety assessments
• Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), clinically significant laboratory test abnormalities, and discontinuation of treatment due to treatment-related AEs serve and hypersensitivity /anaphylactic reactions.
• Number and percentage of subjects with hospitalizations due to any serious adverse events with pulmonary and/or cardiac casue(s), after the first dose of investigational product (IP).
• Number and percentage of subjects with hospitalizations due to any serious adverse events with pulmonary and/or cardiac cause(s)
• Number and percentage of subjects with bone fractures
• Ulna length measurements for indirect measure of growth velocity (cm/year) for subjects under the age of 18

E.5.1.1

Timepoint(s) of evaluation of this end point

Double-blind phase:
Baseline
Week 52

Open-label extension phase:
Week 52
Week 104
Week 156
Week 208

Safety:
From screening throughout week 208

E.5.2

Secondary end point(s)

Double-blind phase:
• Change in percent predicted forced vital capacity (ppFVC) from baseline to Week 52, assessed by spirometry.
• Change in the Grip strength of the hands from baseline to Week 52, assessed by Hand Held Myometry (HHM).
• Change in Left Ventricular Ejection Fraction percentage (LVEF %) from baseline to Week 52, assessed by MRI.
• Change in percent predicted peak expiratory flow (ppPEF) from baseline to Week 52, assessed by spirometry.

Open-label extension phase:
Pulmonary assessment:
• Annual mean change in percent predicted forced vital capacity, assessed by spirometry;
• Annual mean change in percent predicted peak expiratory flow, assessed by spirometry.

Performance assessement:
• Annual mean change in the Grip strength of the hands extremities, assessed by Hand Held Myometry.

Cardiac assessment (Exploratory Assessment):
• Annual mean change in Left Ventricular Ejection Fraction percentage assessed by MRI.
• Annual mean change in Cardiac fibroses score, assessed by Late Gadolinium Enhancement.
• Annual mean change in Myocardial Circumferential Strain [Global Circumferential Strain (GCS)] percentage, assessed by cardiac MRI.

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline
Week 52

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Open-label extension

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

China

United States

Switzerland

Austria

Belgium

Czechia

France

Italy

Netherlands

Spain

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Minors

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-10-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-02

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-08-17

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IMP with orphan designation in the indication
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