Phase 3 Trial of Pamrevlumab or Placebo With Systemic Corticosteroids in Participants With Non-ambulatory Duchenne Muscular Dystrophy (DMD) (LELANTOS-1)

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)

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

Study Overview

• Status: Terminated
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Pamrevlumab; Drug: Corticosteroids; Drug: Placebo

Detailed Description

This is a global, Phase 3, randomized, double-blind trial of pamrevlumab or placebo in combination with systemic corticosteroids in participants with non-ambulatory Duchenne muscular dystrophy, aged 12 years and older. Approximately 90 male participants will be randomized at a 1:1 ratio to Arm A (pamrevlumab + systemic corticosteroid) or Arm B (placebo+ systemic corticosteroid), respectively.

Participants 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.

This trial has 3 study periods:

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

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

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

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

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

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males at least 12 years of age, non-ambulatory at screening initiation
2. Written consent by participant and/or legal guardian as per regional/ country and/or Institutional Review Board (IRB)/Independent Ethics Committee (IEC) requirements
3. Male participants 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.
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 forced vital capacity (FVC) between 45 and 85, inclusive
9. Left ventricular ejection fraction ≥50% as determined by local cardiac MRI read at screening or within 3 months prior to randomization (Day 0)
10. If participants have a history of cardiomyopathy, then participant must be on a stable dose of cardiomyopathy/ heart failure medications (for example, angiotensin converting enzyme inhibitors, aldosterone receptors blockers, angiotensin-receptor blockers, and betablockers) for at least 1 month prior to screening. If participants 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 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 (for example, 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. Agreement to receive annual influenza vaccinations during the course of the study.
13. Adequate renal function: cystatin C ≤1.4 mg/liter (L)

14. Adequate hematology and electrolytes parameters:

    1. Platelets >100,000/microliter (μL)
    2. Hemoglobin >12 grams (g)/deciliter (dL)
    3. Absolute neutrophil count >1500/μL
    4. Serum calcium (Ca), potassium (K), sodium (Na), magnesium (Mg) and phosphorus (P) levels are within a clinically accepted range for DMD participants.

15. Adequate hepatic function:

    1. No history or evidence of liver disease
    2. Gamma glutamyl transferase (GGT) ≤3x upper limit of normal (ULN)
    3. Total bilirubin ≤1.5xULN

Exclusion Criteria:

1. Previous exposure to pamrevlumab
2. BMI ≥40 kg/square meter (m^2) or weight >117 kg

3. History of:

   1. allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies
   2. hypersensitivity to study drug or any component of study drug
   3. 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 (for example, 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

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

   1. Need for intravenous diuretics or inotropic support within 8 weeks prior to screening
   2. Hospitalization for a heart failure exacerbation or arrhythmia within 8 weeks prior to screening
   3. Participants with glomerular filtration rate (GFR) of less than 30 mL/minute (min)/1.73 m^2 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
10. The Investigator judges that the participant 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pamrevlumab; Pamrevlumab 35 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally for up to 52 weeks	Drug: Pamrevlumab; Pamrevlumab per dose and schedule specified in the arm description; Other Names: FG-3019; Drug: Corticosteroids; Systemic deflazacort or equivalent potency of corticosteroids administered orally
Placebo Comparator: Placebo; Matching placebo IV every 2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally for up to 52 weeks	Drug: Corticosteroids; Systemic deflazacort or equivalent potency of corticosteroids administered orally; Drug: Placebo; Matching placebo per schedule specified in the arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Total Score of Performance of Upper Limb (PUL) 2.0 Version at Week 52	The PUL module is an observer-administered performance battery of upper extremity mobility tasks for the shoulder (upper, 6 items, 12 points), elbow (middle, 9 items, 17 points) and wrist/hand (distal, 7 items, 13 points). Higher scores indicate higher level of function. Total score ranges from 0-42 points and is the sum of the scores for the 3 subscales. Analysis was done using a random coefficient model (RCM), which included fixed effects of time (as a continuous variable), treatment, and treatment-by-time interaction, with baseline ordinal PUL entry score as covariate.	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 52, Assessed by Spirometry	FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC was the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) * 100%. Analysis was done using an RCM, which included fixed effects of time (as a continuous variable), treatment, and treatment-by-time interaction, with baseline value as covariate.	Baseline, Week 52
Change From Baseline in the Grip Strength of the Hands at Week 52, Assessed by Hand Held Myometry (HHM)	The HHM was used to measure distal upper arm strength (grip strength). Data has been presented by dominant and non-dominant hand. Grip Strength was analyzed using a MMRM with fixed effects for treatment, visit (as a factor), treatment-by-visit interaction, and covariates (baseline values).	Baseline, Week 52
Change From Baseline in Left Ventricular Ejection Fraction Percentage (LVEF %) at Week 52, Assessed by Magnetic Resonance Imaging (MRI)	LVEF% is an important measure of cardiac function. LVEF is a fraction of blood (in percent) pumped out of the left ventricle of the heart (the main pumping chamber). The LVEF% was analyzed using an analysis of covariance (ANCOVA) model with treatment and baseline value.	Baseline, Week 52
Change From Baseline in Percent Predicted Peak Expiratory Flow (ppPEF) at Week 52, Assessed by Spirometry	The ppPEF is a measure of the maximal or peak flow produced during an exhalation with maximal effort and, as such, is the most effort-dependent measure of lung function. The ppFEV1 was analyzed using an RCM including fixed effects of time, treatment, and treatment-by-time interaction, with baseline as covariate.	Baseline, Week 52

Collaborators and Investigators

• Sponsor: FibroGen

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2020
• Primary Completion (Actual): February 13, 2023
• Study Completion (Actual): August 17, 2023

Study Registration Dates

• First Submitted: April 29, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (Actual): May 1, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Duchenne Muscular Dystrophy, DMD
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: FGCL-3019-093; 2020-000698-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No