A Phase 3 Trial of Pamrevlumab (FG-3019) or Placebo in Combination With Systemic Corticosteroids, in Ambulatory Subjects With Duchenne Muscular Dystrophy (DMD)

Sponsor

FibroGen (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04632940

Collaborator

(none)

Enrollment

Locations

Arms

41.6

Anticipated Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate 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 <12 years).

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy	Drug: Pamrevlumab Drug: Placebo	Phase 3

Detailed Description

This is a global, randomized, double-blind, trial of pamrevlumab or placebo in combination with systemic corticosteroids in subjects with Duchenne muscular dystrophy, aged 6 to <12 years (ambulatory subjects only). Approximately 70 subjects will be randomized at a 1:1 ratio to Arm A (pamrevlumab + systemic deflazacort or equivalent potency of corticosteroids administered orally) or Arm B (placebo+ systemic deflazacort or equivalent potency of corticosteroids administered orally), respectively.

Subjects must be fully informed of the potential benefits of approved products and make an informed decision when participating in a clinical trial in which they could be randomized to placebo.

Subjects will be randomized in a 1:1 ratio to one of the two study treatment arms; pamrevlumab or placebo. Randomization will be stratified by exon 44 deletion.

The main study has three study periods:

Screening period: Up to 4 weeks
Treatment period: 52 weeks
Safety Follow-up period/final assessment: A visit 28 days (+/- 3 Days) and a final safety follow-up phone call 60 days (+ 3 Days) after the last dose

Each subject will receive pamrevlumab or placebo at 35 mg/kg every 2 weeks for up to 52 weeks. Subjects who complete 52 weeks of treatment may be eligible for an open-label extension (OLE), offering extended treatment with pamrevlumab.

Subjects who discontinue study treatment for any reason should be encouraged to return to the investigative site to complete final safety and efficacy assessments.

Study Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official 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)

Actual Study Start Date :

Dec 11, 2020

Anticipated Primary Completion Date :

Aug 31, 2023

Anticipated Study Completion Date :

May 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A pamrevlumab 35 mg/kg IV Q2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally	Drug: Pamrevlumab pamrevlumab 35 mg/kg IV Q2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally Other Names: FG-3019
Placebo Comparator: Arm B matching placebo IV Q2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally	Drug: Placebo matching placebo IV Q2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally

Arm

Intervention/Treatment

Experimental: Arm A

pamrevlumab 35 mg/kg IV Q2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally

Drug: Pamrevlumab

pamrevlumab 35 mg/kg IV Q2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally

Other Names:

FG-3019

Placebo Comparator: Arm B

matching placebo IV Q2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally

Drug: Placebo

matching placebo IV Q2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally

Outcome Measures

Primary Outcome Measures

Ambulatory function assessment: [baseline to Week 52]
Change in NorthStar Ambulatory Assessment (NSAA) Linearized total score

Secondary Outcome Measures

Other Muscle function assessments: [baseline to Week 52]
Change in 4-stair climb Velocity (4SCV) assessment
Other Muscle function assessments: [baseline to Week 52]
Change in the 10-meter walk/run test
Other Muscle function assessments: [baseline to Week 52]
Changes in Time to Stand (TTSTAND)
Other Muscle function assessments: [baseline to Week 52]
Time to Loss of Ambulation (LoA)

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 11 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Age, and consent:

Males at least 6 to <12 years of age at screening initiation
Written consent by legal guardian as per regional/ country and/or IRB/IEC requirements

DMD diagnosis:

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

Pulmonary criteria:

Average (of screening and day 0) percent predicted FVC above 45%
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) or stable dose. A reasonable expectation is that dosage and dosing regimen would not change significantly for the duration of the study.

Performance criteria:

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

Vaccination:

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

Laboratory criteria:

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

Exclusion Criteria:

General Criteria:

Concurrent illness other than DMD that can cause muscle weakness and/or impairment of motor function
Severe intellectual impairment (eg, severe autism, severe cognitive impairment, severe behavioral disturbances) preventing the ability to perform study assessments in the Investigator's judgment
Previous exposure to pamrevlumab
BMI ≥40 kg/m2 or weight >117 kg
History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies
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, golodirsen) within 5 half-lives of screening, whichever is longer with the exception of the systemic corticosteroids, including deflazacort

Pulmonary and Cardiac criteria:

Requires ≥16 hours continuous ventilation
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
Hospitalization due to respiratory failure within the 8 weeks prior to screening
Severe uncontrolled heart failure (NYHA Classes III-IV), including any of the following:
Need for intravenous diuretics or inotropic support within 8 weeks prior to screening
Hospitalization for a heart failure exacerbation or arrhythmia within 8 weeks prior to screening
Arrhythmia requiring anti-arrhythmic therapy
Any other evidence of clinically significant structural or functional heart abnormality

Clinical judgment:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
2	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
3	University of California Davis Children's Hospital	Sacramento	California	United States	95817
4	University of California San Diego Health	San Diego	California	United States	92161
5	Children's Hospital Colorado	Aurora	Colorado	United States	80045
6	University of Florida Health Shands Hospital	Gainesville	Florida	United States	32610
7	Rare Disease Research - Tampa	Tampa	Florida	United States	33614
8	Rare Disease Research Center	Atlanta	Georgia	United States	30329
9	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
10	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
11	University of Kansas Medical Center Research Institute	Fairway	Kansas	United States	66205
12	Kennedy Krieger Institute	Baltimore	Maryland	United States	21205
13	University of Massachusetts Memorial Center	Worcester	Massachusetts	United States	01655
14	C.S. Mott Children's Hospital	Ann Arbor	Michigan	United States	48109-4234
15	Spectrum Health Hospitals Helen DeVos Children's Hospital	Grand Rapids	Michigan	United States	49503
16	Washington University School of Medicine in St. Louis	Saint Louis	Missouri	United States	63110
17	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3026
18	Shriners Hospital for Children	Portland	Oregon	United States	97239
19	Penn State Health Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
20	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
21	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
22	Texas Children's Hospital	Houston	Texas	United States	77030
23	University of Utah Health	Salt Lake City	Utah	United States	84108
24	University of Virginia Children's Hospital	Charlottesville	Virginia	United States	22903
25	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
26	Seattle Children's Hospital	Seattle	Washington	United States	98105
27	Children's Wisconsin Corporate Center	Milwaukee	Wisconsin	United States	53226
28	Murdoch Children's Research Institute	Parkville	Victoria	Australia	3052
29	Klinik Favoriten	Wien	Vienna	Austria	1100
30	Universitair Ziekenhuis Leuven - Campus Gasthuisberg	Leuven	Flemish Brabant	Belgium	3000
31	Centre Hospitalier Régional de la Citadelle	Liège	Liege	Belgium	4000
32	Universitair Ziekenhuis Gent	Gent	Oost-Vlaanderen	Belgium	9000
33	London Health Sciences Centre	London	Ontario	Canada	N6A 5W9
34	Children's Hospital of Chongqing Medical University	Chongqing	Chongqing	China	401122
35	The 1st Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong	China	510080
36	Xiangya Hospital Central South University	Changsha	Hunan	China	410008
37	West China Second University Hospital, Sichuan University	Chengdu	Sichuan	China	610041
38	Peking Union Medical College Hospital, Chinese Academy of Medical Sciences	Beijing		China	100730
39	Hôpital Hautepierre	Strasbourg	Bas-Rhin	France	67200
40	Centre Hospitalier Universitaire Nantes - Hôtel Dieu	Nantes		France	44093
41	Association Institut de Myologie	Paris		France	75012
42	IRRCS Ospedale San Raffaele	Milano	Milan	Italy	20132
43	Istituto di Ricovero e Cura a Carattere Scientifico Eugenio Medea - Lombardia	Bosisio ParIni		Italy	23842
44	Centro Clinico NeMO	Milano		Italy	20162
45	Fondazione Policlinico Universitario Agostino Gemelli	Roma		Italy	168
46	Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo	Roma		Italy
47	Leiden Universitair Medisch Centrum	Leiden		Netherlands
48	Radboud Universitair Medisch Centrum	Nijmegen		Netherlands
49	Hospital Universitari Vall d'Hebrón	Barcelona		Spain	08035
50	Hospital Universitari i Politecnic La Fe de Valencia	Valencia		Spain	46026
51	Leeds Teaching Hospitals NHS Trust	Leeds	England	United Kingdom	LS1 3EX
52	Oxford University Hospitals NHS Foundation Trust	Oxford	England	United Kingdom	OX3 9DU