Phase 3 Trial of Pamrevlumab or Placebo in Combination With Systemic Corticosteroids in Participants With Ambulatory DMD (LELANTOS-2)

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)

To evaluate the efficacy and safety of pamrevlumab versus placebo in combination with systemic corticosteroids administered every 2 weeks in ambulatory participants with Duchenne muscular dystrophy (DMD) (age 6 to <12 years).

Study Overview

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

Detailed Description

This is a global, randomized, double-blind, trial of pamrevlumab or placebo in combination with systemic corticosteroids in participants with DMD, aged 6 to <12 years (ambulatory participants only). Approximately 70 participants 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. Randomization will be stratified by exon 44 deletion for analysis. Stratification has no impact upon treatment assignment nor dosage.

Participants 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.

The main study has 3 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 participant will receive pamrevlumab or placebo at 35 mg/kg every 2 weeks for up to 52 weeks. Participants who complete 52 weeks of treatment may be eligible for an open-label extension (OLE), offering extended treatment with pamrevlumab.

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): 73
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Murdoch Children's Research Institute
• Austria
  • Vienna
    • Wien, Vienna, Austria, 1100
      • Klinik Favoriten
• Belgium
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
  • Liege
    • Liège, Liege, Belgium, 4000
      • Centre Hospitalier Régional de la Citadelle
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • Universitair Ziekenhuis Gent
• 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, 401122
      • Children's Hospital of Chongqing Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The 1st Affiliated Hospital, Sun Yat-sen University
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Second University Hospital, Sichuan University
• France
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire Nantes - Hotel Dieu
  • Paris, France, 75012
    • Association institut de Myologie
  • Bas-Rhin
    • Strasbourg, Bas-Rhin, France, 67200
      • Hôpital Hautepierre
• Italy
  • Bosisio ParIni, Italy, 23842
    • Istituto di Ricovero e Cura a Carattere Scientifico Eugenio Medea - Lombardia
  • Milano, Italy, 20162
    • Centro Clinico Nemo
  • Roma, Italy, 168
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Roma, Italy
    • Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo
  • Milan
    • Milano, Milan, Italy, 20132
      • IRRCS Ospedale San Raffaele
• Netherlands
  • Leiden, Netherlands
    • Leiden Universitair Medisch Centrum
  • Nijmegen, Netherlands
    • Radboud Universitair Medisch Centrum
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
• United Kingdom
  • England
    • Leeds, England, United Kingdom, LS1 3EX
      • Leeds Teaching Hospitals NHS Trust
    • Oxford, England, United Kingdom, OX3 9DU
      • Oxford University Hospitals NHS Foundation Trust
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Sacramento, California, United States, 95817
      • University of California Davis Children's Hospital
    • San Diego, California, United States, 92161
      • University of California San Diego Health
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Health Shands Hospital
    • Tampa, Florida, United States, 33614
      • Rare Disease Research - Tampa
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Rare Disease Research Center
  • 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 Hospitals and Clinics
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Medical Center Research Institute
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Center
  • 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 St. Louis
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3026
      • Cincinnati Children's Hospital Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Shriners Hospital for Children
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Children's Hospital
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Wisconsin Corporate Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Age, and consent:

1. Males at least 6 to <12 years of age 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

   DMD diagnosis:

3. Medical history includes diagnosis of DMD and confirmed Duchenne mutation, including status of exon 44 using a validated genetic test.

   Pulmonary criteria:

4. Average (of screening and Day 0) percent predicted forced vital capacity (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 (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.

   Performance criteria:

6. Able to complete 6-minute walking distance (6MWD) test with a distance of at least 270 meters but no more than 450 meters on two occasions within 3 months prior to randomization 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 magnetic resonance imaging (MRI) test for the lower extremities vastus lateralis muscle.

   Vaccination:

9. Agreement to receive annual influenza vaccinations during the conduct of the study.

   Laboratory criteria:

10. Adequate renal function: cystatin C ≤1.4 mg/liter (L)

11. 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

12. 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:

General Criteria:

1. Concurrent illness other than DMD that can cause muscle weakness and/or impairment of motor function
2. Severe intellectual impairment (for example, severe autism, severe cognitive impairment, severe behavioral disturbances) preventing the ability to perform study assessments in the Investigator's judgment
3. Previous exposure to pamrevlumab
4. Body mass index (BMI) ≥40 kg/square meter (m^2) or weight >117 kg

5. 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

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

   Pulmonary and Cardiac 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 the 8 weeks prior to screening

10. Severe uncontrolled heart failure (New York Heart Association [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
11. Arrhythmia requiring anti-arrhythmic therapy

12. Any other evidence of clinically significant structural or functional heart abnormality

    Clinical judgment:

13. 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, surgical 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 will be administered 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; Placebo will be administered 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 North Star Ambulatory Assessment (NSAA) Total Score at Week 52	The NSAA consisted of 17 activities, each scored as 0 (activity could not be performed), 1 (modified method but achieved goal without physical assistance from another), or 2 (normal, achieved goal without assistance). The sum of these 17 scores was used to form a total score ranging from 0 (worst) to 34 (fully independent function). If fewer than 15 of the 17 activities were performed, the total score was considered missing. If 15 to 16 activities were performed, the total score was calculated by multiplying the sum of the scores in the x activities that were performed by 17/x. If an activity could not be performed due to disease progression/loss of ambulation, a score of 0 was assigned. Higher scores indicated better functioning. Least square (LS) mean and standard error (SE) were analyzed using a mixed model for repeated measure (MMRM).	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 4-Stair Climb Velocity (4SCV) Assessment at Week 52	The 4SCV (centimeters [cm]/second [sec]) was calculated as the ratio of the total height (cm) of stairs climbed divided by the number of seconds taken to complete the 4-stair climb.	Baseline, Week 52
Change From Baseline in the 10-Meter Walk/Run Test at Week 52	The time (in sec) required for a participant to run or walk a distance of 10 meters as quickly as possible was calculated as velocity (meters/sec).	Baseline, Week 52
Change From Baseline in Time to Stand (TTSTAND) at Week 52	The time (in sec) required for a participant to stand from supine position has been reported. A longer time taken reflected a worse outcome.	Baseline, Week 52
Time to Loss of Ambulation (LoA) From Baseline to Week 52	Time (days) to LoA was defined as the number of days from randomization to the date of LoA, or all-cause death based on observed data, whichever occurred earlier during the on-study period. Median time (days) to LoA was calculated using Kaplan Meier Survival Estimates.	Baseline to Week 52

Collaborators and Investigators

• Sponsor: FibroGen

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2021
• Primary Completion (Actual): June 12, 2023
• Study Completion (Actual): December 14, 2023

Study Registration Dates

• First Submitted: November 12, 2020
• First Submitted That Met QC Criteria: November 12, 2020
• First Posted (Actual): November 17, 2020

Study Record Updates

• Last Update Posted (Actual): August 26, 2024
• Last Update Submitted That Met QC Criteria: August 1, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Nervous System Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Neuromuscular Diseases; Muscular Diseases; Muscular Dystrophies; Genetic Diseases, X-Linked; Duchenne Muscular Dystrophy, DMD; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic
• 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-3019-094; 2020-000699-39 (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