Trial of Pamrevlumab (FG-3019), a Monoclonal Antibody to Connective Tissue Growth Factor, in Non-Ambulatory Subjects With Duchenne Muscular Dystrophy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- FibroGen
- 入组人数
- 21
- 试验地点
- 10
- 主要终点
- Annual Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 104
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Pamrevlumab
Participants will receive pamrevlumab 35 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion every 2 weeks for a minimum of 104 weeks. Participants who complete the main study, will continue to receive pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of up to 208 weeks in the OLE.
干预措施: Pamrevlumab (Drug)
结局指标
主要结局
Annual Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 104
时间窗: 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.
次要结局
- Change From Baseline in Percent Predicted Forced Expiratory Volume at 1 Second (ppFEV1) at Week 104(Baseline, Week 104)
- Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 104(Baseline, Week 104)
- Change From Baseline in Left Ventricular Ejection Fraction Percentage (LVEF%) at Week 104(Baseline, Week 104)
- Change From Baseline in Performance of Upper Limb (PUL) Total Score at Week 104(Baseline, Week 104)
- Change From Baseline in Grip Strength by Hand, as Measured by Hand Held Myometry (HHM) at Week 104(Baseline, Week 104)
- Change From Baseline in Pinch Strength, as Measured by HHM at Week 104(Baseline, Week 104)
- Change From Baseline in Cardiac Fibrosis (Scar Mass), as Measured by Magnetic Resonance Imaging (MRI) at Week 104(Baseline, Week 104)
- Change From Baseline in Upper Arm (Biceps Brachii MRI) Muscle Fat and Fibrosis Score, as Measured by MRI at Week 104(Baseline, Week 104)
- Change From Baseline in Fat Fraction Percentage (%F), as Measured by MRI at Week 104(Baseline, Week 104)