Phase 3 Trial of Pamrevlumab or Placebo in Combination With Systemic Corticosteroids in Participants With Ambulatory DMD

Duchenne Muscular Dystrophy Clinical Trial

— LELANTOS-2  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04632940
• Other study ID #: FGCL-3019-094
• Secondary ID: 2020-000699-39
• Status: Terminated
• Phase: Phase 3
• Start date: December 11, 2020
• Est. completion date: December 12, 2023

Study information

• Verified date: May 2024
• Source: FibroGen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 73
• Est. completion date: December 12, 2023
• Est. primary completion date: June 12, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Years to 11 Years

Eligibility

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

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Pamrevlumab
Pamrevlumab will be administered per dose and schedule specified in the arm description.
• Placebo
Placebo will be administered per schedule specified in the arm description.
• Corticosteroids
Systemic deflazacort or equivalent potency of corticosteroids administered orally

Locations

Country	Name	City	State
Australia	Murdoch Children's Research Institute	Parkville	Victoria
Austria	Klinik Favoriten	Wien	Vienna
Belgium	Universitair Ziekenhuis Gent	Gent	Oost-Vlaanderen
Belgium	Universitair Ziekenhuis Leuven - Campus Gasthuisberg	Leuven	Flemish Brabant
Belgium	Centre Hospitalier Régional de la Citadelle	Liège	Liege
Canada	London Health Sciences Centre	London	Ontario
China	Peking Union Medical College Hospital, Chinese Academy of Medical Sciences	Beijing
China	Xiangya Hospital Central South University	Changsha	Hunan
China	West China Second University Hospital, Sichuan University	Chengdu	Sichuan
China	Children's Hospital of Chongqing Medical University	Chongqing	Chongqing
China	The 1st Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
France	Centre Hospitalier Universitaire Nantes - Hôtel Dieu	Nantes
France	Association Institut de Myologie	Paris
France	Hôpital Hautepierre	Strasbourg	Bas-Rhin
Italy	Istituto di Ricovero e Cura a Carattere Scientifico Eugenio Medea - Lombardia	Bosisio ParIni
Italy	Centro Clinico NeMO	Milano
Italy	IRRCS Ospedale San Raffaele	Milano	Milan
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo	Roma
Netherlands	Leiden Universitair Medisch Centrum	Leiden
Netherlands	Radboud Universitair Medisch Centrum	Nijmegen
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds	England
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford	England
United States	C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	Rare Disease Research Center	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	University of Virginia Children's Hospital	Charlottesville	Virginia
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Kansas Medical Center Research Institute	Fairway	Kansas
United States	University of Florida Health Shands Hospital	Gainesville	Florida
United States	Spectrum Health Hospitals Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Penn State Health Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Texas Children's Hospital	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Children's Wisconsin Corporate Center	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Shriners Hospital for Children	Portland	Oregon
United States	University of California Davis Children's Hospital	Sacramento	California
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri
United States	University of Utah Health	Salt Lake City	Utah
United States	University of California San Diego Health	San Diego	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Rare Disease Research - Tampa	Tampa	Florida
United States	University of Massachusetts Memorial Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
FibroGen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  France,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52		Baseline, Week 52
Secondary	Change From Baseline in 4-Stair Climb Velocity (4SCV) Assessment at Week 52		Baseline, Week 52
Secondary	Change From Baseline in the 10-Meter Walk/Run Test at Week 52		Baseline, Week 52
Secondary	Change From Baseline in Time to Stand (TTSTAND) at Week 52		Baseline, Week 52
Secondary	Time to Loss of Ambulation (LoA) From Baseline to Week 52		Baseline to Week 52