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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04371666




Registration number
NCT04371666
Ethics application status
Date submitted
29/04/2020
Date registered
1/05/2020

Titles & IDs
Public title
Phase 3 Trial of Pamrevlumab or Placebo With Systemic Corticosteroids in Participants With Non-ambulatory Duchenne Muscular Dystrophy (DMD)
Scientific 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)
Secondary ID [1] 0 0
2020-000698-26
Secondary ID [2] 0 0
FGCL-3019-093
Universal Trial Number (UTN)
Trial acronym
LELANTOS-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Duchenne Muscular Dystrophy 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pamrevlumab
Treatment: Drugs - Placebo
Treatment: Drugs - Corticosteroids

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

Placebo comparator: Placebo - Matching placebo IV every 2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally for up to 52 weeks


Treatment: Drugs: Pamrevlumab
Pamrevlumab per dose and schedule specified in the arm description

Treatment: Drugs: Placebo
Matching placebo per schedule specified in the arm description

Treatment: Drugs: Corticosteroids
Systemic deflazacort or equivalent potency of corticosteroids administered orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in the Total Score of Performance of Upper Limb (PUL) 2.0 Version at Week 52
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [1] 0 0
Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 52, Assessed by Spirometry
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [2] 0 0
Change From Baseline in the Grip Strength of the Hands at Week 52, Assessed by Hand Held Myometry (HHM)
Timepoint [2] 0 0
Baseline, Week 52
Secondary outcome [3] 0 0
Change From Baseline in Left Ventricular Ejection Fraction Percentage (LVEF %) at Week 52, Assessed by Magnetic Resonance Imaging (MRI)
Timepoint [3] 0 0
Baseline, Week 52
Secondary outcome [4] 0 0
Change From Baseline in Percent Predicted Peak Expiratory Flow (ppPEF) at Week 52, Assessed by Spirometry
Timepoint [4] 0 0
Baseline, Week 52

Eligibility
Key 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
Minimum age
12 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/08/2023
Sample size
Target
Accrual to date
Final
98
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Murdoch Children's Research Institute - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oregon
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
Austria
State/province [21] 0 0
Vienna
Country [22] 0 0
Belgium
State/province [22] 0 0
Gent
Country [23] 0 0
Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Belgium
State/province [24] 0 0
Liège
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
China
State/province [26] 0 0
Chongqing
Country [27] 0 0
China
State/province [27] 0 0
Sichuan
Country [28] 0 0
China
State/province [28] 0 0
Beijing
Country [29] 0 0
Czechia
State/province [29] 0 0
Brno
Country [30] 0 0
Czechia
State/province [30] 0 0
Prague
Country [31] 0 0
France
State/province [31] 0 0
Nantes
Country [32] 0 0
France
State/province [32] 0 0
Paris
Country [33] 0 0
France
State/province [33] 0 0
Strasbourg cedex
Country [34] 0 0
Israel
State/province [34] 0 0
Tel Aviv
Country [35] 0 0
Italy
State/province [35] 0 0
Lecco
Country [36] 0 0
Italy
State/province [36] 0 0
Milan
Country [37] 0 0
Italy
State/province [37] 0 0
Rome
Country [38] 0 0
Netherlands
State/province [38] 0 0
Gelderland
Country [39] 0 0
Netherlands
State/province [39] 0 0
Leiden
Country [40] 0 0
Spain
State/province [40] 0 0
Alicante
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Valencia
Country [43] 0 0
Switzerland
State/province [43] 0 0
Bern
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Leeds
Country [45] 0 0
United Kingdom
State/province [45] 0 0
London
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
FibroGen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04371666