Trial of Pamrevlumab (FG-3019), a Monoclonal Antibody to Connective Tissue Growth Factor, in Non-Ambulatory Subjects with Duchenne Muscular Dystrophy
Study ID: STU 032016-030
This study will be an open-label, single arm study of up to 22 subjects. Patients will be evaluated for inclusion during the Screening Period of up to 4 weeks (28 days). Potential subjects may be re-screened if initial screening procedures lie outside the 28-day screening period prior to planned study entry. eligible patients will receive FG-3019 (35 mg/kg, every 2 weeks) for up to 52 weeks (initial Phase). Subjects who achieve a [LessThanorequalTo] 5% decline from baseline in FVC % predicted by Week 52 may continue on extended treatment, at the same dose/schedule, for an additional 26 weeks (total of 78 weeks of treatment) with prior FibroGen medical monitor approval. if a subject has a weight change of more than 10%, the total FG-3019 dose will be adjusted based on the new weight. FG-3019 will be administered by iV infusion, using an infusion set with a sterile, nonpyrogenic, low-protein-binding in-line filter (0.2-micron pore size). Subjects should be carefully monitored for reaction during the first infusion with a physician available as needed. Subjects will remain at the study site for 1 hour after the end of the infusion for clinical observation for the initial 3 infusions. if a subject does not have an infusion reaction (Section 8.2.3) during 3 consecutive infusions, the infusion duration may be shortened to as little as 30 minutes provided the investigator thinks infusing this fluid load is safe. The following assessments are relevant to the assessment of efficacy: pulmonary function tests (FVC, mean inspiratory flow (MiF), peak expiratory flow), Brooke upper extremity Rating Scale, Performance of the upper Limb, pinch strength, grip strength, cardiac MRi, and muscle MRi. The following assessments are relevant to the assessment for safety: physical examinations, vital signs, laboratory assessment (complete blood count, gamma glutamyl transferase (GGT), total bilirubin, alkaline phosphatase (aLP), aspartate transaminase (aST), alanine transaminase (aLT), and albumin, creatine kinase (CK), and cystatin C). other laboratory assessments include: plasma samples for pharmacokinetics, plasma and urine samples for CTGF concentrations, human anti-human antibody (HaHa), and blood samples for biomarkers. endpoints efficacy Primary endpoint - The change from baseline to Week 52 in in annual forced vital capacity (FVC) (% predicted) during treatment of pamrevlumab compared with the estimated annual change prior to pamrevlumab treatment.. Secondary endpoints: * Change from baseline to Week 52 in forced expiratory volume (FeV1), maximum inspiratory pressure (MiP), maximum expiratory pressure (MeP), peak expiratory flow (PeF), peak cough flow * Change in LVeF from baseline to Week 52 * Change from baseline to Week 52 in Performance of upper Limb (PuL) Score * Change from baseline to Week 52 in grip strength, pinch strength, and Brooke scale for upper extremity * Change from baseline to Week 52 in cardiac fibrosis score assessed by MRi * Change from baseline to Week 52 in upper arm (bicep) muscle fat and fibrosis assessed by MRi exploratory, Pharmacokinetics, Pharmacodynamics: in the first 12 subjects to have complete PK/PD samples: * Pharmacokinetic (PK) profile of pamrevlumab (including Cmin, Cmax, auCtau, and t1/2) o in the overall population o in subjects 12 to 16 years of age, inclusive o in subjects older than 16 years o Comparison of PK profiles across age groups * Plasma and urine CTGF * Creatine kinase (CK) * Circulating biomarkers. Safety - adverse events (aes), serious adverse events (Saes), clinical laboratory tests and discontinuation of treatment for treatment-related aes serve as the safety assessments for this trial.
1. At least 12 years of age 2. Written consent/assent by patient and/or legal guardian as per regional and/or IRB requirements 3. Non-ambulatory 4. Brooke Score for Arms and Shoulders <=5 5. Diagnosis of DMD by medical history and confirmed Duchenne mutation in available genetic testing using a validated genetic test 6. Able to perform spirometry 7. Able to undergo cardiac and extremity (upper arm) MRI 8. Percent predicted FVC between 40 and 90, inclusive 9. At least one historical FVC % predicted value within 18 months of baseline 10. Left ventricular ejection fraction >45% as determined by cardiac MRI at screening or within 3 months prior to Day 0 11. Subjects currently receiving heart failure cardiac medications (e.g. angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, and beta-blockers) must achieve a stable regimen for at least 3 months prior to screening 12. 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 13. Received pneumococcal vaccine and is receiving annual influenza vaccinations 14. Adequate renal function: cystatin C <=1.4 mg/L 15. Adequate hematological function: a. Platelets >100,000/mcL b. Hemoglobin >12 g/dL c. Absolute neutrophil count >1500 /[MICRO-SYMBOL]L 16. Adequate hepatic function: a. No history or evidence of liver disease b. Gamma glutamyl transferase (GGT) <=3 x upper limit of normal (ULN) c. Total bilirubin <=1.5xULN 17. If sexually active, will use medically accepted contraceptives during participation in the study and for 3 months after the last dose of study drug
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Diana Patricia Castro