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

Sponsor
FibroGen (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04371666
Collaborator
(none)
90
Enrollment
53
Locations
2
Arms
26
Anticipated Duration (Months)
1.7
Patients Per Site
0.1
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 in subjects with non-ambulatory Duchenne muscular dystrophy (age 12 years and older).

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This is a global, randomized, double-blind trial of pamrevlumab or placebo in combination with systemic corticosteroids in subjects with non-ambulatory Duchenne muscular dystrophy, aged 12 years and older. Approximately 90 male subjects will be randomized at a 1:1 ratio to Arm A (pamrevlumab + systemic corticosteroid) or Arm B (placebo+ systemic corticosteroid), respectively.

Subjects must be fully informed of the potential benefits of approved products and make an informed decision that they prefer to participate 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 in combination with systemic steroids.

This trial has three study periods:

  • Screening period: Up to 4 weeks

  • Treatment period: 52 weeks

  • Safety Follow-up period/final assessment: 4 weeks (Week 56 (+/-3 days))

In the screening period, subjects will be evaluated per the protocol inclusion/exclusion criteria to determine eligibility for participation in this trial.

During the treatment period, each subject will receive pamrevlumab or placebo at 35 mg/kg every 2 weeks for up to 52 weeks.

Subjects who complete the 52-week study (either arm) may be eligible for rollover into an open-label extension treatment (OLE) with pamrevlumab + systemic corticosteroids.

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 :
90 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 Subjects With Non-ambulatory Duchenne Muscular Dystrophy (DMD)
Actual Study Start Date :
Jul 30, 2020
Anticipated Primary Completion Date :
Aug 31, 2022
Anticipated Study Completion Date :
Sep 30, 2022

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

    		•
    Experimental: 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

    1. Functional assessment: Change in the total score of Performance of Upper Limb (PUL) 2.0 version [Baseline to Week 52]

    Secondary Outcome Measures

    1. Pulmonary assessment: Change in percent predicted forced vital capacity (ppFVC) assessed by spirometry. [baseline to Week 52]

    2. Pulmonary assessment: Change in percent predicted peak expiratory flow (ppPEF) assessed by spirometry [baseline to Week 52]

    3. Performance assessment: Change in the Grip strength of the hands assessed by Hand Held Myometry (HHM). [baseline to Week 52]

    4. Cardiac assessment: Change in Left Ventricular Ejection Fraction percentage (LVEF %) assessed by MRI. [baseline to Week 52]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    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 3 months after the last dose of study drug.

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

    5. Brooke Score for Arms and Shoulders ≤5

    6. Able to undergo MRI test for the upper arm extremities (Biceps Brachii muscle) and cardiac muscle

    7. Able to perform spirometry

    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. Prior diagnosis of cardiomyopathy, subjects must be on a stable regimen dose for cardiomyopathy/ heart failure medications (e.g., angiotensin converting enzyme inhibitors, aldosterone receptors blockers, angiotensin-receptor blockers, and betablockers) for at least 1 month prior to screening

    11. 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.

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

    13. Adequate renal function: cystatin C ≤1.4 mg/L

    14. Adequate hematology and electrolytes parameters:

    15. Platelets >100,000/mcL

    16. Hemoglobin >12 g/dL

    17. Absolute neutrophil count >1500 /μL

    18. Serum calcium (Ca), potassium (K), sodium (Na), magnesium (Mg) and phosphorus (P) levels are within a clinically accepted range

    19. Adequate hepatic function:

    20. No history or evidence of liver disease

    21. Gamma glutamyl transferase (GGT) ≤3x upper limit of normal (ULN)

    22. Total bilirubin ≤1.5xULN

    Exclusion Criteria:

    1. Previous exposure to pamrevlumab

    2. BMI ≥40 kg/m2 or weight >117 kg

    3. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies

    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, ataluren, golodirsen) within 5 half-lives of screening, whichever is longer, with the exception of the systemic corticosteroids, including deflazacort

    5. Severe uncontrolled heart failure (NYHA Classes III-IV), including any of the following:

    6. Need for intravenous diuretics or inotropic support within 8 weeks prior to screening

    7. Hospitalization for a heart failure exacerbation or arrhythmia within 8 weeks prior to screening

    8. Arrhythmia requiring anti-arrhythmic therapy

    9. Requires ≥16 hours continuous ventilation

    10. Hospitalization due to respiratory failure within the 8 weeks prior to screening

    11. 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

    12. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arkansas Children's Little Rock Arkansas United States 72202
    2 University of California Los Angeles Medical Center Los Angeles California United States 90045
    3 UC Davis Health Sacramento California United States 95817
    4 Children's Hospital Colorado Aurora Colorado United States 80045
    5 Rare Disease Research, LLC Atlanta Georgia United States 30318
    6 Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois United States 60611
    7 University of Iowa Iowa City Iowa United States 52242
    8 University of Kansas Medical Center Fairway Kansas United States 66205
    9 Kennedy Krieger Institute Baltimore Maryland United States 21205
    10 UMASS Med School Worcester Massachusetts United States 01655
    11 C.S. Mott Children's Hospital Ann Arbor Michigan United States 48109-4234
    12 Spectrum Health Hospitals Helen DeVos Children's Hospital Grand Rapids Michigan United States 49503
    13 Washington University School of Medicine in Saint Louis Saint Louis Missouri United States 63110
    14 Carolinas HealthCare System Neurosciences Institute-Neurology - Charlotte Charlotte North Carolina United States 28207
    15 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    16 Nationwide Children's Hospital Columbus Ohio United States 43205-2664
    17 Shriners Hospital for Children Portland Oregon United States 97239
    18 Penn State Health Children's Hospital Hershey Pennsylvania United States 17033
    19 The Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    20 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    21 Children's Health Dallas/UTSW Dallas Texas United States 75207
    22 University of Utah Health Salt Lake City Utah United States 84108
    23 Children's Specialty Group - Medical Center Office Norfolk Virginia United States 23507
    24 Seattle Children's Hospital Seattle Washington United States 98105
    25 Murdoch Children's Research Institute Parkville Victoria Australia 3052
    26 Klinik Favoriten Vienna Austria 1100
    27 Universitair Ziekenhuis Gent Gent Belgium 9000
    28 Universitair Ziekenhuis Leuven - Campus Gasthuisberg Leuven Belgium 3000
    29 Centre Hospitalier Régional de la Citadelle Liège Belgium 4000
    30 London Health Sciences Centre London Ontario Canada N6A 5W9
    31 Children's Hospital of Chongqing Medical University Chongqing Chongqing China 400015
    32 West China Second University Hospital, Sichuan University Chengdu Sichuan China 610041
    33 Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Beijing China 100730
    34 Fakultní Nemocnice Brno - Dětská Nemocnice Brno Czechia 613 00
    35 Klinika dÄ>tské neurologie, Neuromuskulární centrum Prague Czechia 150 06
    36 CHU de Nantes - Hotel Dieu Nantes France 44093
    37 Association Institut de Myologie Paris France 75012
    38 Hopital Hautepierre Strasbourg cedex France 67098
    39 The Chaim Sheba Medical Center Tel Aviv Israel 5265601
    40 The Edith Wolfson Medical Center Tel Aviv Israel 5822012
    41 Istituto di Ricovero e Cura a Carattere Scientifico Eugenio Medea - Lombardia Lecco Italy 23842
    42 IRRCS Ospedale San Raffaele Milan Italy 20132
    43 Fondazione Policlinico Universitario Agostino Gemelli Rome Italy 00168
    44 Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo Rome Italy 165
    45 Radboud Universitair Medisch Centrum Nijmegen Gelderland Netherlands 6525
    46 Leiden Universitair Medisch Centrum Leiden Netherlands 2333 ZA
    47 Hospital General Universitario de Alicante Alicante Spain 3010
    48 Hospital Universitari Vall d'Hebrón Barcelona Spain 08035
    49 Hospital Universitari i Politecnic La Fe Valencia Spain 46026
    50 Inselspital Universitätsspital Bern Bern Switzerland 3010
    51 Leeds Teaching Hospitals NHS Trust Leeds United Kingdom LS1 3EX
    52 University College London Hospitals NHS Foundation Trust London United Kingdom WC1N 3BG
    53 Oxford University Hospitals NHS Foundation Trust Oxford United Kingdom OX3 9DU

    Sponsors and Collaborators

    • FibroGen

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    FibroGen
    ClinicalTrials.gov Identifier:
    NCT04371666
    Other Study ID Numbers:
    • FGCL-3019-093
    First Posted:
    May 1, 2020
    Last Update Posted:
    Jan 24, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by FibroGen
    Duchenne Muscular Dystrophy, DMD
    Additional relevant MeSH terms:
    Muscular Dystrophies
    Muscular Dystrophy, Duchenne

    Study Results

    No Results Posted as of Jan 24, 2022