Trial of Pamrevlumab (FG-3019), in Non-Ambulatory Participants With Duchenne Muscular Dystrophy (DMD)

• Sponsor: FibroGen (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02606136
• Collaborator: (none)
• Enrollment: 21
• Locations: 10
• Arm: 1
• Anticipated Duration (Months): 84.9
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy	Drug: Pamrevlumab	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Trial of Pamrevlumab (FG-3019), a Monoclonal Antibody to Connective Tissue Growth Factor, in Non-Ambulatory Subjects With Duchenne Muscular Dystrophy
• Actual Study Start Date: Jan 4, 2016
• Actual Primary Completion Date: May 7, 2020
• Anticipated Study Completion Date: Jan 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pamrevlumab Participants will receive pamrevlumab 35 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion every 2 weeks for a minimum of 104 weeks.	Drug: Pamrevlumab; Pamrevlumab, 10 milligrams (mg)/milliliter (mL), single dose vials; Other Names: Monoclonal Antibody to Connective tissue growth factor (CTGF), FG-3019

Outcome Measures

Primary Outcome Measures

1. Annual Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 104 [Baseline, 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

1. Change From Baseline in Percent Predicted Forced Expiratory Volume at 1 Second (ppFEV1) at Week 104 [Baseline, 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.

2. Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 104 [Baseline, 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.

3. Change From Baseline in Left Ventricular Ejection Fraction Percentage (LVEF%) at Week 104 [Baseline, 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.

4. Change From Baseline in Performance of Upper Limb (PUL) Total Score at Week 104 [Baseline, 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.

5. Change From Baseline in Grip Strength by Hand, as Measured by Hand Held Myometry (HHM) at Week 104 [Baseline, 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.

6. Change From Baseline in Pinch Strength, as Measured by HHM at Week 104 [Baseline, 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.

7. Change From Baseline in Cardiac Fibrosis (Scar Mass), as Measured by Magnetic Resonance Imaging (MRI) at Week 104 [Baseline, 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.

8. Change From Baseline in Upper Arm (Biceps Brachii MRI) Muscle Fat and Fibrosis Score, as Measured by MRI at Week 104 [Baseline, 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.

9. Change From Baseline in Fat Fraction Percentage (%F), as Measured by MRI at Week 104 [Baseline, 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

1. Platelets >100,000/microliter (μL)

2. Hemoglobin >12 grams (g)/deciliter (dL)

3. Absolute neutrophil count >1500/μL

• Adequate hepatic function

1. No history or evidence of liver disease

2. Gamma glutamyl transferase (GGT) ≤3 x upper limit of normal (ULN)

3. 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:

1. Need for intravenous diuretics or inotropic support within 3 months prior to screening

2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	David Geffen School of Medicine at UCLA	Los Angeles	California	United States	90095
2	University of California San Francisco - Benioff Children's Hospital	San Francisco	California	United States	94143
3	Children's Hospital Colorado	Aurora	Colorado	United States	80045
4	Rare Disease Research	Atlanta	Georgia	United States	30318
5	Boston Children's Hospital	Boston	Massachusetts	United States	02115
6	Washington University in St. Louis School of Medicine	Saint Louis	Missouri	United States	63110
7	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
8	Shriner's Hospital for Children - Portland	Portland	Oregon	United States	97239
9	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
10	Children's Medical Center Ambulatory Care Pavilion	Dallas	Texas	United States	75207

Sponsors and Collaborators

• FibroGen

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Sep 27, 2019
• Statistical Analysis Plan - Jun 25, 2020

More Information

Publications

None provided.

• Responsible Party: FibroGen
• ClinicalTrials.gov Identifier: NCT02606136
• Other Study ID Numbers: FGCL-3019-079
• First Posted: Nov 17, 2015
• Last Update Posted: Dec 30, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Keywords provided by FibroGen: Duchenne; muscular; dystrophy; DMD; non-ambulatory
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne; Mitogens

Study Results

Participant Flow

Pre-assignment Detail	All participants who completed the main portion of the study for a minimum of 104 weeks (2 years) were rolled over to an open-label extension (OLE) for up to an additional 208 weeks (4 years). Some participants remained in the main study for up to 206 weeks before rolling over to the OLE. The last Week 104 visit for the primary endpoint occurred on 07 May 2020.

Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion every 2 weeks for a minimum of 104 weeks.
Period Title: Overall Study
STARTED	21
Received at Least 1 Dose of Study Drug	21
COMPLETED	15
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of 104 weeks.
Overall Participants	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.99 (3.277)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	21 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 9.5%
Not Hispanic or Latino	19 90.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	20 95.2%
More than one race	0 0%
Unknown or Not Reported	0 0%
Percent Predicted Forced Vital Capacity (ppFVC) (percentage of predicted FVC) [Mean (Full Range) ]
Mean (Full Range) [percentage of predicted FVC]	54.15
Percent Predicted Peak Expiratory Flow (PEF) (percentage of predicted PEF) [Mean (Full Range) ]
Mean (Full Range) [percentage of predicted PEF]	54.66
Percent Predicted Forced Expiratory Volume at 1 Second (ppFEV1) (percentage of predicted FEV1) [Mean (Full Range) ]
Mean (Full Range) [percentage of predicted FEV1]	53.815
Left Ventricular Ejection Fraction Percentage (LVEF%) (percentage of LVEF) [Mean (Full Range) ]
Mean (Full Range) [percentage of LVEF]	56.992
Performance of Upper Limb (PUL) Total Score (unit on a scale) [Mean (Full Range) ]
Mean (Full Range) [unit on a scale]	24.4
Pinch Strength, as Measured by Hand Held Myometry (HHM) (newton) [Mean (Full Range) ]
Dominant Pinch Best Result	17.003
Non-Dominant Pinch Best Result	16.607
Grip Strength by Hand, as Measured by HHM (newton) [Mean (Full Range) ]
Dominant Grip Best Result	45.861
Non-Dominant Grip Best Result	41.977
Cardiac Fibrosis Score (Scar Mass), as Measured by Magnetic Resonance Imaging (MRI) (grams) [Mean (Full Range) ]
Mean (Full Range) [grams]	24.100
Upper Arm (Biceps Brachii MRI) Muscle Fat and Fibrosis Score (unit on a scale) [Mean (Full Range) ]
Mean (Full Range) [unit on a scale]	8.01
Fat Fraction Percentage (%F), as Measured by MRI (percentage of fat) [Mean (Full Range) ]
Mean (Full Range) [percentage of fat]	22.07

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who enrolled in the study.

Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of 104 weeks.
Measure Participants	21
Least Squares Mean (Standard Error) [percentage of predicted FVC]	-8.15 (1.079)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who enrolled in the study.

Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of 104 weeks.
Measure Participants	21
Least Squares Mean (Standard Error) [percentage of predicted FEV1]	-8.32 (1.217)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who enrolled in the study.

Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of 104 weeks.
Measure Participants	21
Least Squares Mean (Standard Error) [percentage of predicted PEF]	-7.13 (2.313)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who enrolled in the study.

Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of 104 weeks.
Measure Participants	21
Least Squares Mean (Standard Error) [percentage of LVEF]	-2.73 (1.651)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who enrolled in the study.

Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of 104 weeks.
Measure Participants	21
Least Squares Mean (Standard Error) [unit on a scale]	-4.14 (0.651)

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who enrolled in the study.

Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of 104 weeks.
Measure Participants	21
Dominant Grip Best Result	-2.52 (3.610)
Non-Dominant Grip Best Result	-1.31 (3.591)

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who enrolled in the study.

Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of 104 weeks.
Measure Participants	21
Dominant Pinch Best Result	-4.24 (1.547)
Non-Dominant Pinch Best Result	-3.46 (1.378)

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who enrolled in the study. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of 104 weeks.
Measure Participants	20
Least Squares Mean (Standard Error) [grams]	3.74 (4.475)

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who enrolled in the study. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of 104 weeks.
Measure Participants	12
Least Squares Mean (Standard Error) [unit on scale]	-2.22 (1.088)

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT population included all participants who enrolled in the study. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of 104 weeks.
Measure Participants	9
Least Squares Mean (Standard Error) [percentage of fat]	4.49 (2.030)

Adverse Events

Time Frame	Baseline up to Week 104
Adverse Event Reporting Description	Safety population included participants who received at least one dose of study drug.
Arm/Group Title	Pamrevlumab
Arm/Group Description	Participants received pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of 104 weeks.
All Cause Mortality
	Pamrevlumab
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Serious Adverse Events
	Pamrevlumab
	Affected / at Risk (%)	# Events
Total	6/21 (28.6%)
Gastrointestinal disorders
Food poisoning	1/21 (4.8%)
General disorders
Adverse drug reaction	1/21 (4.8%)
Infections and infestations
Pneumonia	1/21 (4.8%)
Injury, poisoning and procedural complications
Concussion	1/21 (4.8%)
Femur fracture	1/21 (4.8%)
Skull fracture	1/21 (4.8%)
Metabolism and nutrition disorders
Metabolic acidosis	1/21 (4.8%)
Renal and urinary disorders
Hydronephrosis	1/21 (4.8%)
Nephrolithiasis	1/21 (4.8%)
Vascular disorders
Hypotension	1/21 (4.8%)
Other (Not Including Serious) Adverse Events
	Pamrevlumab
	Affected / at Risk (%)	# Events
Total	21/21 (100%)
Blood and lymphatic system disorders
Leukopenia	1/21 (4.8%)
Lymphocytosis	1/21 (4.8%)
Neutropenia	1/21 (4.8%)
Cardiac disorders
Palpitations	3/21 (14.3%)
Myocardial fibrosis	1/21 (4.8%)
Supraventricular extrasystoles	1/21 (4.8%)
Tachycardia	1/21 (4.8%)
Ear and labyrinth disorders
Ear pain	3/21 (14.3%)
Cerumen impaction	1/21 (4.8%)
Ear swelling	1/21 (4.8%)
Endocrine disorders
Adrenal insufficiency	1/21 (4.8%)
Eye disorders
Cataract	2/21 (9.5%)
Gastrointestinal disorders
Vomiting	10/21 (47.6%)
Nausea	7/21 (33.3%)
Abdominal pain upper	5/21 (23.8%)
Diarrhoea	5/21 (23.8%)
Abdominal distension	2/21 (9.5%)
Dyspepsia	2/21 (9.5%)
Abdominal discomfort	1/21 (4.8%)
Abdominal pain	1/21 (4.8%)
Aphthous ulcer	1/21 (4.8%)
Constipation	1/21 (4.8%)
Gastrooesophageal reflux disease	1/21 (4.8%)
Tooth impacted	1/21 (4.8%)
General disorders
Pyrexia	8/21 (38.1%)
Axillary pain	1/21 (4.8%)
Chest pain	1/21 (4.8%)
Chills	1/21 (4.8%)
Cyst	1/21 (4.8%)
Extravasation	1/21 (4.8%)
Fatigue	1/21 (4.8%)
Infusion site pain	1/21 (4.8%)
Injection site pain	1/21 (4.8%)
Malaise	1/21 (4.8%)
Nodule	1/21 (4.8%)
Oedema peripheral	1/21 (4.8%)
Pain	1/21 (4.8%)
Peripheral swelling	1/21 (4.8%)
Immune system disorders
Hypersensitivity	2/21 (9.5%)
Infections and infestations
Nasopharyngitis	11/21 (52.4%)
Upper respiratory tract infection	5/21 (23.8%)
Sinusitis	3/21 (14.3%)
Influenza	2/21 (9.5%)
Pneumonia	1/21 (4.8%)
Bronchitis	1/21 (4.8%)
Candida infection	1/21 (4.8%)
Cellulitis	1/21 (4.8%)
Eye infection	1/21 (4.8%)
Hordeolum	1/21 (4.8%)
Localised infection	1/21 (4.8%)
Pharyngitis	1/21 (4.8%)
Viral upper respiratory tract infection	1/21 (4.8%)
Injury, poisoning and procedural complications
Muscle strain	2/21 (9.5%)
Ankle fracture	1/21 (4.8%)
Bone contusion	1/21 (4.8%)
Compression fracture	1/21 (4.8%)
Contusion	1/21 (4.8%)
Fall	1/21 (4.8%)
Foot fracture	1/21 (4.8%)
Ligament sprain	1/21 (4.8%)
Procedural nausea	1/21 (4.8%)
Scratch	1/21 (4.8%)
Soft tissue injury	1/21 (4.8%)
Spinal compression fracture	1/21 (4.8%)
Sunburn	1/21 (4.8%)
Wound	1/21 (4.8%)
Investigations
Cystatin C increased	2/21 (9.5%)
Weight decreased	2/21 (9.5%)
Blood pressure increased	1/21 (4.8%)
Bone density decreased	1/21 (4.8%)
Electrocardiogram PR shortened	1/21 (4.8%)
Eosinophil count increased	1/21 (4.8%)
Neutrophil count increased	1/21 (4.8%)
White blood cell count increased	1/21 (4.8%)
Metabolism and nutrition disorders
Fluid overload	1/21 (4.8%)
Musculoskeletal and connective tissue disorders
Back pain	8/21 (38.1%)
Myalgia	5/21 (23.8%)
Arthralgia	2/21 (9.5%)
Joint swelling	1/21 (4.8%)
Limb discomfort	1/21 (4.8%)
Muscle spasms	1/21 (4.8%)
Musculoskeletal disorder	1/21 (4.8%)
Osteoporosis	1/21 (4.8%)
Nervous system disorders
Headache	14/21 (66.7%)
Dizziness	3/21 (14.3%)
Migraine	2/21 (9.5%)
Sinus headache	2/21 (9.5%)
Paraesthesia	1/21 (4.8%)
Somnolence	1/21 (4.8%)
Psychiatric disorders
Anxiety	3/21 (14.3%)
Depression	2/21 (9.5%)
Affect lability	1/21 (4.8%)
Renal and urinary disorders
Nephrolithiasis	1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Cough	9/21 (42.9%)
Sinus congestion	6/21 (28.6%)
Oropharyngeal pain	4/21 (19%)
Rhinorrhoea	4/21 (19%)
Nasal congestion	3/21 (14.3%)
Productive cough	2/21 (9.5%)
Dyspnoea	1/21 (4.8%)
Paranasal sinus discomfort	1/21 (4.8%)
Sleep apnoea syndrome	1/21 (4.8%)
Throat irritation	1/21 (4.8%)
Skin and subcutaneous tissue disorders
Erythema	2/21 (9.5%)
Rash	2/21 (9.5%)
Skin discolouration	2/21 (9.5%)
Alopecia	1/21 (4.8%)
Dry skin	1/21 (4.8%)
Surgical and medical procedures
Tooth extraction	1/21 (4.8%)
Vascular disorders
Flushing	1/21 (4.8%)
Hypertension	1/21 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The multisite consortium can publish any time after the data is collected and analyzed by FibroGen. The investigator can only publish after the multisite consortium publishes (or tries to publish and fails). FibroGen has 60 days to review a publication and can extend the embargo up to an additional 120 days (or 180 total).