Duchenne's Muscular Dystrophy MedDRA version: 19.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: PF-06252616
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: PF-06252616
Current Sponsor code: PF-06252616
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Pfizer Inc. 235 East 42nd Street, New York, NY 10017
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Ambulatory boys age 6 to 0.2 mg/kg) in dosage or dose regimen (not related to body weight change) for at least 3 months immediately prior to signing the informed consent and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study. 6. Adequate hepatic and renal function on screening laboratory assessments: •GGT =upper limit of normal (ULN). •Alkaline phosphatase =ULN. •Total Bilirubin =ULN. •Serum Albumin=LLN. •Serum creatinine =ULN. 7. No underlying disposition for iron accumulation on screening laboratory assessments: •Serum Iron=1.2 x ULN. •Serum Ferritin =140 ng/mL. •% Transferrin Saturation =50%. 8. No underlying disposition for bleeding disorder on screening laboratory assessments: •PT/INR =1.25 x ULN. •aPTT =1.25x ULN. •Fecal occult blood is negative. If the fecal occult blood is positive due to known pre-exiting medical condition (eg, any cause of rectal bleeding; hemorrhoids, anal fissure) that is not considered to be clinically significant by the investigator, the subject may be included. 9. Iron content estimate on the screening liver MRI is within the normal range as determined by R2* value (R2*=75 Hz at 1.5 T or R2*=139 Hz at 3.0 T). *Note: The 4 stair climb is expressed as a velocity in the inclusion criteria rather than a time in seconds in an attempt to reduce the risk of subjects purposefully manipulating their performance at screening in order to enroll. To determine eligibility subjects must have a 4 SC that is =2.5s but =12s on the screening assessment. It is not necessary to calculate the velocity. Are the trial subjects under 18? yes Number of subjects for this age range: 105 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects with known cognitive impairment or behavioral issues that would impede the ability to follow instructions. 2. History of major surgical procedure within 6 weeks of signing the informed consent or planned surgery during the study. 3. Any injury which may impact functional testing. Previous injuries must be fully healed prior to consenting. Prior lower limb fractures must be fully healed and at least 3 months from injury date. 4. Presence or history of other musculoskeletal or neurologic disease or somatic disorder not related to DMD including pulmonary and cardiac disease. 5. Compromised cardiac function (left ventricular ejection fraction <55% as determined on a screening cardiac MRI or echocardiogram). Subjects may be receiving ACE (angiotensin-converting-enzyme) inhibitors, beta blockers, ARB (angiotensin II receptor blocker) or aldosterone blocker/thiazide diuretic; however they must have initiated treatment more than 3 months prior to screening to ensure stable therapy. 6. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including uncontrolled hypertension), hepatic, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). 7. Documented history of iron overload including hemochromatosis, beta thalassemia major, beta thalassemia intermedia or hemolytic anemia. 8. Unwilling or unable (eg, metal implants, requires sedation) to undergo examination with closed MRI without sedation. 9. Participation in other studies involving investigational drug(s) for a minimum of 30 days or within 5 half-lives (whichever is longer) prior to signing the informed consent and/or during study participation. 10. Current or prior treatment with anti-myostatin, exon skipping, nonsense mutation targeted therapies ever or more than 30 days of treatment with utrophin modifiers and treatment with utrophin modifiers within 30 days prior to signing the informed consent and/or during study participation. 11. Current or prior treatment within the past 3 months with androgens or human growth hormone. 12. Current treatment with immunosuppressant therapies (other than glucocorticoid steroids), aminoglycosides (eg, gentamicin), multi-vitamins with iron and iron supplements and other investigational therapies (including idebenone). 13. History of allergic or anaphylactic reaction to a therapeutic or diagnostic protein or additives of this investigational product (histidine, sucrose, edetic acid [ethylenediaminetetraacetic acid], and polysorbate 80). 14. Have suicidal ideation and behavior associated with actual intent and/or method and/or plan and/or action (eg, self-harming behaviors) in the past 6 months based on the Columbia-Suicide Severity Rating Scale (C-SSRS Children’s Baseline/Screening Appendix 1) or at baseline (C-SSRS Children’s Since Last Visit Appendix 2). 15. Subjects who, in the opinion of the investigator, are biologically capable of having children and are sexually active who are unwilling or unable to use a condom to prevent potential transfer of exposure to drug through semen; male subjects of childbearing potential, with their female partners at risk for pregnancy, who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol (in addition to the condom to prevent potential transfer of drug through semen) for the duration of the s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To determine the safety and tolerability of multiple ascending repeat IV doses of PF-06252616 in ambulatory boys with DMD. - To demonstrate the efficacy of treatment with IV doses of PF-06252616 based on an observed mean change from baseline on function (4 Stair Climb) as compared to placebo following 49 weeks of treatment.;Secondary Objective: - To characterize the effects of PF-06252616 on muscle strength and other functional assessments compared to placebo - To evaluate the PD activity of PF-06252616 based on the percent change of muscle volume from baseline as compared to placebo - To evaluate the PD profile of PF-06252616 based on GDF-8 (myostatin) modulation in serum - To characterize the PK profile of PF-06252616 - To evaluate the immunogenicity of PF-06252616 - To characterize the long-term effects following approximately 2-years of treatment with PF-06252616 on functional assessments compared to historical control. - To characterize the effects of PF-06252616 on muscle strength and functional assessments compared to placebo in subset of subjects who may demonstrate a rapid disease decline and with relatively low variability over a one-year period.;Primary end point(s): Safety: - Incidence of dose limiting or intolerability treatment related AEs by Week 49. - Incidence, severity and causal relationship of treatment emergent AEs (TEAEs) and withdrawals due to TEAEs by Week 49. - Incidence and magnitude of abnormal laboratory findings (clinical laboratory tests [hematology, chemistry, GGT, PT, aPTT, creatine kinase, amylase, serum ferritin, serum iron, Total Iron Binding Capacity (TIBC), % transferrin saturation, hormone [luteinizing hormone [LH], follicle stimulating hormone [FSH], thyroxine [T4], thyroid stimulating hormone [TSH], fecal occult and urinalysis) by Week 49. - Abnormal and clinically relevant changes in liver MRI by Week 45 and physical examinations (including nose and throat mucosal exam and Tanner stage), weight, vital signs, | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Strength and Function: - Mean change from baseline as compared to placebo on function tests including, Forced Vital Capacity (FVC), Northstar Ambulatory Assessment (NSAA), range of motion (ROM), Performance of Upper Limb (PUL), 6MWD at Week 17, 33 and 49. Mean change from baseline as compared to placebo on the 4 SC at Week 17 and 33. - Mean change from baseline as compared to placebo on muscle strength by myometry at Week 17, 33 and 49. - In subject randomized to sequence 1, mean change from baseline as compared to historical control on functional tests including, 4SC, FVC, NSAA, PUL, 6MWD at Week 97. - In a pre-specified subset of subjects who may demonstrate a rapid disease decline and with relatively low variability, the mean change from baseline as compared to placebo on function testes including, 4SC, FVC, NSAA, PUL, 6MWD at Week 17, 33 and 49. The definition of this subgroup will be detailed in the Statistical Analysis Plan (SAP). - In a pre-specified subset of subjects who may demonstrate a rapid disease decline, the mean change from baseline as compared to placebo on muscle strength at Week 17, 33 and 49. Pharmacodynamic: - Mean percent change as compared to placebo in muscle volume as measured on MRI by Week 17, 33 and 49. Within subject change from baseline in thigh muscle volume through week 97. - Noncompartmental GDF-8 parameters such as AUCt(GDF-8), AUCt,ss(GDF-8), CGDF-8(0), Cmax,ss(GDF-8), Tmax(GDF-8), Ctrough,ss(GDF-8), and Css,av (GDF-8), may be determined. Pharmacokinetic: - All subjects receiving active drug: Cmax, Tmax, and Ctrough for all visits with PF-06252616 dosing. - All subjects receiving active drug in Period 1 followed by placebo in Period 2 (Sequence 2): terminal t½ for Visit 19 (last dose in Period 1) using concentration data from samples collected during placebo treatment in Period 2. - Subjects with additional PK sampling receiving active drug in Period 1: AUCt and Cav for Visits 3, 9, and | — |
Countries
Australia, Bulgaria, Canada, Italy, Japan, Poland, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer Inc
Outcome results
None listed