Back to resultsTrial of Pamrevlumab (FG-3019), in Non-Ambulatory Participants With Duchenne Muscular Dystrophy (DMD) (MISSION)
Primary Purpose
Duchenne Muscular Dystrophy
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pamrevlumab
Sponsored by
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy focused on measuring Duchenne, muscular, dystrophy, DMD, non-ambulatory
Eligibility Criteria
Inclusion Criteria:
- Written consent/assent by participant and/or legal guardian as per regional and/or institutional review board (IRB) requirements
- Non-ambulatory
- Brooke Score for Arms and Shoulders ≤5
- Diagnosis of DMD by medical history and confirmed Duchenne mutation in available genetic testing using a validated genetic test
- Able to perform spirometry
- Able to undergo cardiac and extremity (upper arm) MRI
- Percent predicted FVC between 40 and 90, inclusive
- At least one historical ppFVC predicted value within 18 months of baseline
- Left ventricular ejection fraction ≥ 45% as determined by cardiac MRI at screening or within 3 months prior to Day 0
- Participants currently receiving heart failure cardiac medications (for example, angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, and beta-blockers) must achieve a stable regimen for at least 3 months prior to screening
- On a stable dose of corticosteroids for a minimum of 6 months prior to screening with no substantial change in dosage for a minimum of 3 months (except for adjustments for changes in body weight) prior to screening and no foreseen change in corticosteroid use during the course of study participation
- Received pneumococcal vaccine and is receiving annual influenza vaccinations
- Adequate renal function: cystatin C ≤1.4 mg/liter (L)
Adequate hematological function
- Platelets >100,000/microliter (μL)
- Hemoglobin >12 grams (g)/deciliter (dL)
- Absolute neutrophil count >1500/μL
Adequate hepatic function
- No history or evidence of liver disease
- Gamma glutamyl transferase (GGT) ≤3 x upper limit of normal (ULN)
- Total bilirubin ≤1.5 x ULN
- If sexually active, will use medically accepted contraceptives during participation in the study and for 3 months after the last dose of study drug
Exclusion Criteria:
- Requires ≥16 hours continuous ventilation
- Prior or ongoing medical condition that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of 156 weeks of treatment and follow-up would be completed, or could impair the assessment of study results
- Anticipated spine surgery within 156 weeks
Severe uncontrolled heart disease, including any of the following:
- Need for intravenous diuretics or inotropic support within 3 months prior to screening
- Hospitalization for a heart failure exacerbation or arrhythmia in last 3 months
- Arrhythmia requiring anti-arrhythmic therapy
- Hospitalization due to respiratory failure in the last 6 weeks
- Poorly controlled asthma or underlying lung disease such as bronchopulmonary dysplasia
- Known or suspected active hepatitis B or C or history of human immunodeficiency virus (HIV)
- Body mass index (BMI) ≥40 kilograms (kg)/square meter (m^2) or weight >117 kg
- Exposure to another investigational drug or another approved product for DMD (for example, eteplirsen or golodirsen) within 28 days prior to start of study treatment
- Exposure to another investigational drug or another approved product for DMD (e.g. eteplirsen) within 28 days prior to start of study treatment (or 5 half-lives of the product whichever is longer) prior to first screening visit with the exception of deflazacort. Use of deflazacort, if regarded by the principal investigator as standard of care, is allowed.
Sites / Locations
- David Geffen School of Medicine at UCLA
- University of California San Francisco - Benioff Children's Hospital
- Children's Hospital Colorado
- Rare Disease Research
- Boston Children's Hospital
- Washington University in St. Louis School of Medicine
- Cincinnati Children's Hospital Medical Center
- Shriner's Hospital for Children - Portland
- The Children's Hospital of Philadelphia
- Children's Medical Center Ambulatory Care Pavilion
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pamrevlumab
Arm Description
Participants will receive pamrevlumab 35 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion every 2 weeks for a minimum of 104 weeks.
Outcomes
Primary Outcome Measures
Annual Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 104
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 a random coefficient model (RCM), which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Secondary Outcome Measures
Change From Baseline in Percent Predicted Forced Expiratory Volume at 1 Second (ppFEV1) at Week 104
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Predicted FEV1 is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FEV1= (observed value)/(predicted value) * 100%. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 104
Percent predicted PEF 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. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Change From Baseline in Left Ventricular Ejection Fraction Percentage (LVEF%) at Week 104
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). Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Change From Baseline in Performance of Upper Limb (PUL) Total Score at Week 104
The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into shoulder level (4 items), elbow level (9 items), and distal level (8 items) dimensions. Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. Each dimension was scored separately with a maximum score of 16 for shoulder level, 34 for elbow level, and 24 for distal level. Total score was calculated by adding the 3 level scores, with a maximum global score of 74 (total score range = 0-74). Higher score = better outcome. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Change From Baseline in Grip Strength by Hand, as Measured by Hand Held Myometry (HHM) at Week 104
The HHM was used to measure distal upper arm strength (grip strength). Data has been presented by dominant and non-dominant hand. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Change From Baseline in Pinch Strength, as Measured by HHM at Week 104
The HHM was used to measure distal upper arm strength (pinch strength). Data has been presented by dominant and non-dominant hand. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Change From Baseline in Cardiac Fibrosis (Scar Mass), as Measured by Magnetic Resonance Imaging (MRI) at Week 104
Cardiac MRI was used to assess the cardiac fibrosis by detecting the presence of late gadolinium enhancement (LGE), a marker for myocardial fibrosis. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Change From Baseline in Upper Arm (Biceps Brachii MRI) Muscle Fat and Fibrosis Score, as Measured by MRI at Week 104
T2-mapping with MRI was conducted to measure upper arm muscle fibrosis and fat in the biceps brachii muscle. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect. The visual score for muscle fat and fibrosis will be assessed using a modified 5-point Mercuri score in which 0 = normal muscle appearance and 5 = complete replacement of muscle by connective tissue and fat, where a lower score indicated visually healthier muscle. Change from baseline was calculated as the score at Week 104 - the score at baseline.
Change From Baseline in Fat Fraction Percentage (%F), as Measured by MRI at Week 104
Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02606136
Brief Title
Trial of Pamrevlumab (FG-3019), in Non-Ambulatory Participants With Duchenne Muscular Dystrophy (DMD)
Acronym
MISSION
Official Title
Trial of Pamrevlumab (FG-3019), a Monoclonal Antibody to Connective Tissue Growth Factor, in Non-Ambulatory Subjects With Duchenne Muscular Dystrophy
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor Decision
Study Start Date
January 4, 2016 (Actual)
Primary Completion Date
May 7, 2020 (Actual)
Study Completion Date
August 7, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
FibroGen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 2, open-label, single arm trial of pamrevlumab (FG-3019) to estimate pamrevlumab's safety and efficacy in non-ambulatory participants with DMD.
Detailed Description
The study will include a screening period, main study period, open-label extension (OLE) period, and follow-up period 4 weeks after the last dose. All participants who complete the main portion of the study for a minimum of 104 weeks (2 years) will be rolled over to an OLE for up to an additional 208 weeks (4 years).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy
Keywords
Duchenne, muscular, dystrophy, DMD, non-ambulatory
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pamrevlumab
Arm Type
Experimental
Arm Description
Participants will receive pamrevlumab 35 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion every 2 weeks for a minimum of 104 weeks.
Intervention Type
Drug
Intervention Name(s)
Pamrevlumab
Other Intervention Name(s)
Monoclonal Antibody to Connective tissue growth factor (CTGF), FG-3019
Intervention Description
Pamrevlumab, 10 milligrams (mg)/milliliter (mL), single dose vials
Primary Outcome Measure Information:
Title
Annual Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 104
Description
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 a random coefficient model (RCM), which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Time Frame
Baseline, Week 104
Secondary Outcome Measure Information:
Title
Change From Baseline in Percent Predicted Forced Expiratory Volume at 1 Second (ppFEV1) at Week 104
Description
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Predicted FEV1 is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FEV1= (observed value)/(predicted value) * 100%. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Time Frame
Baseline, Week 104
Title
Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 104
Description
Percent predicted PEF 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. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Time Frame
Baseline, Week 104
Title
Change From Baseline in Left Ventricular Ejection Fraction Percentage (LVEF%) at Week 104
Description
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). Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Time Frame
Baseline, Week 104
Title
Change From Baseline in Performance of Upper Limb (PUL) Total Score at Week 104
Description
The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into shoulder level (4 items), elbow level (9 items), and distal level (8 items) dimensions. Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. Each dimension was scored separately with a maximum score of 16 for shoulder level, 34 for elbow level, and 24 for distal level. Total score was calculated by adding the 3 level scores, with a maximum global score of 74 (total score range = 0-74). Higher score = better outcome. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Time Frame
Baseline, Week 104
Title
Change From Baseline in Grip Strength by Hand, as Measured by Hand Held Myometry (HHM) at Week 104
Description
The HHM was used to measure distal upper arm strength (grip strength). Data has been presented by dominant and non-dominant hand. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Time Frame
Baseline, Week 104
Title
Change From Baseline in Pinch Strength, as Measured by HHM at Week 104
Description
The HHM was used to measure distal upper arm strength (pinch strength). Data has been presented by dominant and non-dominant hand. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Time Frame
Baseline, Week 104
Title
Change From Baseline in Cardiac Fibrosis (Scar Mass), as Measured by Magnetic Resonance Imaging (MRI) at Week 104
Description
Cardiac MRI was used to assess the cardiac fibrosis by detecting the presence of late gadolinium enhancement (LGE), a marker for myocardial fibrosis. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Time Frame
Baseline, Week 104
Title
Change From Baseline in Upper Arm (Biceps Brachii MRI) Muscle Fat and Fibrosis Score, as Measured by MRI at Week 104
Description
T2-mapping with MRI was conducted to measure upper arm muscle fibrosis and fat in the biceps brachii muscle. Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect. The visual score for muscle fat and fibrosis will be assessed using a modified 5-point Mercuri score in which 0 = normal muscle appearance and 5 = complete replacement of muscle by connective tissue and fat, where a lower score indicated visually healthier muscle. Change from baseline was calculated as the score at Week 104 - the score at baseline.
Time Frame
Baseline, Week 104
Title
Change From Baseline in Fat Fraction Percentage (%F), as Measured by MRI at Week 104
Description
Analysis was done using an RCM, which included visit in years (as a continuous variable), and baseline efficacy as fixed effects, the intercept and the linear slope of visit as random effect, and individual participants as participant effect.
Time Frame
Baseline, Week 104
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written consent/assent by participant and/or legal guardian as per regional and/or institutional review board (IRB) requirements
Non-ambulatory
Brooke Score for Arms and Shoulders ≤5
Diagnosis of DMD by medical history and confirmed Duchenne mutation in available genetic testing using a validated genetic test
Able to perform spirometry
Able to undergo cardiac and extremity (upper arm) MRI
Percent predicted FVC between 40 and 90, inclusive
At least one historical ppFVC predicted value within 18 months of baseline
Left ventricular ejection fraction ≥ 45% as determined by cardiac MRI at screening or within 3 months prior to Day 0
Participants currently receiving heart failure cardiac medications (for example, angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, and beta-blockers) must achieve a stable regimen for at least 3 months prior to screening
On a stable dose of corticosteroids for a minimum of 6 months prior to screening with no substantial change in dosage for a minimum of 3 months (except for adjustments for changes in body weight) prior to screening and no foreseen change in corticosteroid use during the course of study participation
Received pneumococcal vaccine and is receiving annual influenza vaccinations
Adequate renal function: cystatin C ≤1.4 mg/liter (L)
Adequate hematological function
Platelets >100,000/microliter (μL)
Hemoglobin >12 grams (g)/deciliter (dL)
Absolute neutrophil count >1500/μL
Adequate hepatic function
No history or evidence of liver disease
Gamma glutamyl transferase (GGT) ≤3 x upper limit of normal (ULN)
Total bilirubin ≤1.5 x ULN
If sexually active, will use medically accepted contraceptives during participation in the study and for 3 months after the last dose of study drug
Exclusion Criteria:
Requires ≥16 hours continuous ventilation
Prior or ongoing medical condition that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of 156 weeks of treatment and follow-up would be completed, or could impair the assessment of study results
Anticipated spine surgery within 156 weeks
Severe uncontrolled heart disease, including any of the following:
Need for intravenous diuretics or inotropic support within 3 months prior to screening
Hospitalization for a heart failure exacerbation or arrhythmia in last 3 months
Arrhythmia requiring anti-arrhythmic therapy
Hospitalization due to respiratory failure in the last 6 weeks
Poorly controlled asthma or underlying lung disease such as bronchopulmonary dysplasia
Known or suspected active hepatitis B or C or history of human immunodeficiency virus (HIV)
Body mass index (BMI) ≥40 kilograms (kg)/square meter (m^2) or weight >117 kg
Exposure to another investigational drug or another approved product for DMD (for example, eteplirsen or golodirsen) within 28 days prior to start of study treatment
Exposure to another investigational drug or another approved product for DMD (e.g. eteplirsen) within 28 days prior to start of study treatment (or 5 half-lives of the product whichever is longer) prior to first screening visit with the exception of deflazacort. Use of deflazacort, if regarded by the principal investigator as standard of care, is allowed.
Facility Information:
Facility Name
David Geffen School of Medicine at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California San Francisco - Benioff Children's Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rare Disease Research
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Washington University in St. Louis School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Shriner's Hospital for Children - Portland
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Medical Center Ambulatory Care Pavilion
City
Dallas
State/Province
Texas
ZIP/Postal Code
75207
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35204752
Citation
Rayego-Mateos S, Morgado-Pascual JL, Lavoz C, Rodrigues-Diez RR, Marquez-Exposito L, Tejera-Munoz A, Tejedor-Santamaria L, Rubio-Soto I, Marchant V, Ruiz-Ortega M. CCN2 Binds to Tubular Epithelial Cells in the Kidney. Biomolecules. 2022 Feb 3;12(2):252. doi: 10.3390/biom12020252.
Results Reference
derived
Learn more about this trial
Trial of Pamrevlumab (FG-3019), in Non-Ambulatory Participants With Duchenne Muscular Dystrophy (DMD)
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