Clinical trial NCT02907619: An Open-label Extension Study To Evaluate Safety Of PF-06252616 In Boys With Duchenne Muscular Dystrophy
Official title: A MULTICENTER, OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG TERM SAFETY OF PF-06252616 IN BOYS WITH DUCHENNE MUSCULAR DYSTROPHY
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne muscular dystrophy, myostatin, open-label
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-09-20
Enrollment: 59
Sex: MALE
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Primary purpose: TREATMENT

Brief summary: This study is an open-label extension to protocol B5161002 and will provide an assessment of the long term safety, efficacy, pharmacodynamics and pharmacokinetics of intravenous dosing of PF 06252616 in boys with Duchenne muscular dystrophy. Approximately 105 eligible subjects will be assigned to receive a monthly individualized maximum tolerated dose based on their tolerability profile/data from B5161002. This study will not contain a placebo comparator. Subjects will undergo safety evaluations (Laboratory, cardiac monitoring, physical exams, x-ray, MRI), functional capacity evaluations (4 stair climb, range of motion, strength testing, Northstar Ambulatory Assessment, upper limb functional testing, six minute walk test and pulmonary function tests) and pharmacokinetic testing.


Eligibility criteria: Inclusion Criteria:

1. Subjects with Duchenne muscular dystrophy who enrolled and completed study B5161002.
2. Signed and dated informed consent document (ICD) indicating that the subject's parent or legal guardian/caregiver has been informed of all pertinent aspects of the study.
3. Subjects and their legal guardians/caregivers who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
4. Subject have;

   1. Adequate hepatic function on screening laboratory assessments
   2. GLDH less than 20 units/liter (2 x upper limit of normal \[ULN\])
   3. Iron content estimate on the liver MRI within the normal range.

Exclusion Criteria:

1. Unwilling or unable (eg, metal implants) to undergo examination with closed MRI.
2. All male subjects who are able to father children and are sexually active and at risk for impregnating a female partner, who are unwilling or unable to use a highly effective method of contraception. In addition, all sexually active male subjects who are unwilling or unable to prevent potential transfer of and exposure to drug through semen to their partners by using a condom consistently and correctly. .
3. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are related to Pfizer employees directly involved in the conduct of the study.
4. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation.
5. Participation in other studies involving investigational drug(s), with the exception of B5161002.
6. History of allergic or anaphylactic reaction to a therapeutic or diagnostic protein or additives of this investigational product.

Primary outcomes:
measure: Number of Participants With Dose Reduced or Temporary Discontinuation Due to AEs
timeFrame: 2 Years
measure: Number of Participants With Severe Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 2 Years
measure: Number of Participants Who Discontinued From the Study Due to TEAEs
timeFrame: 2 Years
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology
timeFrame: 2 Years
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Coagulation
timeFrame: 2 Years
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function
timeFrame: 2 Years
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Renal Function
timeFrame: 2 Years
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes
timeFrame: 2 Years
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones
timeFrame: 2 Years
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry
timeFrame: 2 Years
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis
timeFrame: 2 Years
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Fecal Blood
timeFrame: 2 Years
measure: Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline
timeFrame: Baseline, Weeks 13, 25, 37, 49, 61, 73 and 85.
measure: Number of Participants With Significant Results of Physical Examinations Including Nose and Throat Mucosal Examinations
timeFrame: 2 Years
measure: Summary of Pubertal Development by Tanner Stage
timeFrame: Screening, Baseline, Week 49.
measure: Summary of Testicular Volume
timeFrame: Screening, Baseline, Week 49.
measure: Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline
timeFrame: 2 Years
measure: Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - Overall Baseline
timeFrame: 2 Years
measure: Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - B5161004 Baseline
timeFrame: 2 Years
measure: Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - Overall Baseline
timeFrame: 2 Years
measure: Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria
timeFrame: Screening and Week 49.
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - B5161004 Baseline
timeFrame: Baseline and Week 49.
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - Overall Baseline
timeFrame: Baseline, Weeks 49, 97, 146.
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - B5161004 Baseline
timeFrame: Baseline, Week 49.
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - Overall Baseline
timeFrame: Baseline, Weeks 49, 97, 146.
measure: Bone Age to Chronological Age Ratio
timeFrame: Baseline and Week 49.
measure: Whole Body and Spine DXA: Bone Mineral Density Z-Score, Height Adjusted Over Time
timeFrame: Screening (Week 97 visit within parent study B5161002) and Week 49
measure: Number of Participants With Suicidal Ideation or Suicidal Behavior
timeFrame: 2 Years
Secondary outcomes:
measure: Change From Baseline on the 4 Stair Climb (4SC) - B5161004 Baseline
timeFrame: Baseline, Weeks 13, 25, 49, 73.
measure: Change From Baseline on the 4SC - Overall Baseline
timeFrame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
measure: Change From Baseline on the Forced Vital Capacity (FVC) - B5161004 Baseline
timeFrame: Baseline, Weeks 13, 25, 49 and 73.
measure: Change From Baseline on the FVC - Overall Baseline
timeFrame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
measure: Change From Baseline on the Northstar Ambulatory Assessment (NSAA) Score - B5161004 Baseline
timeFrame: Baseline, Weeks 13, 25, 49, 73.
measure: Change From Baseline on the NSAA Score - Overall Baseline
timeFrame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
measure: Change From Baseline on the NSAA - Time to Stand From Supine - B5161004 Baseline
timeFrame: Baseline, Weeks 13, 25, 49, 73.
measure: Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline
timeFrame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
measure: Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - B5161004 Baseline
timeFrame: Baseline, Weeks 13, 25, 49, 73.
measure: Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline
timeFrame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
measure: Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline
timeFrame: Baseline, Weeks 13, 25, 49 and 73.
measure: Change From Baseline on the Ankle ROM - Overall Baseline
timeFrame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
measure: Change From Baseline on the Performance of Upper Limb (PUL) Overall Score - B5161004 Baseline
timeFrame: Baseline, Weeks 13, 25, 49 and 73.
measure: Change From Baseline on the PUL Overall Score - Overall Baseline
timeFrame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
measure: Change From Baseline on the Six Minute Walk Distance (6MWD) - B5161004 Baseline
timeFrame: Baseline, Weeks 13, 25, 49 and 73.
measure: Change From Baseline on the 6MWD - Overall Baseline
timeFrame: Baseline,Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
measure: Change From Baseline on the Forced Expiratory Volume in One Second (FEV1) - B5161004 Baseline
timeFrame: Baseline, Weeks 13, 25, 49 and 73.
measure: Change From Baseline on the Peak Expiratory Flow Rate (PEFR)- B5161004 Baseline
timeFrame: Baseline, Weeks 13, 25, 49 and 73.
measure: Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline
timeFrame: Baseline, Weeks 13, 25, 49, 73.
measure: Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline
timeFrame: Baseline,Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
measure: Serum PF-06252616 (Domagrozumab) Concentration Versus Time Summary
timeFrame: Weeks 1, 25, 49 and 73
measure: Number of Participants With Anti-drug Antibodies (ADA) Development
timeFrame: Weeks 1, 25, 49, 73 and Early Termination
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA/UCLA Neurology
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Pharmacy
state: California
city: Los Angeles
country: United States
facility: UCLA (David Geffen School of Medicine), Department of Orthopedic Surgery
state: California
city: Los Angeles
country: United States
facility: UCLA Clinical & Translational Research Center
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: Iowa City
country: United States
facility: University of Iowa ICTS, Clinical Research Unit
state: Iowa
city: Baltimore
country: United States
facility: Kennedy Krieger Institute Out-patient Center
state: Maryland
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Investigational Drug Service
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Children's Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: (For Drug deliveries) IDS Pharmacy
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis Childrens's Hospital
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center, Lenox Baker Children's Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University, Investigational Drug Pharmacy
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Center for Clinical and Translational Sciences
state: Utah
city: Salt Lake City
country: United States
facility: Utah Center for Advanced Imaging and Research (UCAIR)
state: Utah
city: Salt Lake City
country: United States
facility: Investigational Drug Services
state: Utah
city: Salt Lake City
country: United States
facility: Utah Program for Inherited Neuromuscular Disorder
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah School of Medicine
state: Utah
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: UBC Children's and Women's Health Centre of British Columbia
state: British Columbia
city: London
country: Canada
facility: Children's Hospital- London Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Centre de Readaptation Marie Enfant (CRME)
state: Quebec
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Genova
country: Italy
facility: UOC Farmacia - Istituto Gianna Gaslini,
city: Genova
country: Italy
facility: UOC Medicina Fisica Riabilitativa - Istituto G. Gaslini
city: Genova
country: Italy
facility: UOC Neurologia Pediatrica e Malattie Muscolari Istituto Gianna Gaslini
city: Genova
country: Italy
facility: UOC Radiologia - Istituto Gianna Gaslini,
city: Genova
country: Italy
facility: UOS Dipartimentale Endocrinologia Clinica Sperimentale - Ist.
city: Rome
country: Italy
facility: Dipartimento Pediatrico Universitario-Ospedaliero Endocrinologia
city: Rome
country: Italy
facility: Farmacia Ospedaliera, IRCCS Ospedale Pediatrico Bambino Gesu
city: Rome
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu - Centro Trials
city: Rome
country: Italy
facility: U.O. Malattie Neuromuscolari e Neurodegenerative, IRCCS Ospedale Pediatrico Bambino Gesu
city: Nishinomiya-shi
country: Japan
facility: Hyogo college of medicine hospital
state: Hyogo
city: Kodaira
country: Japan
facility: National Center of Neurology and Psychiatry
state: Tokyo
city: London
country: United Kingdom
facility: Dubowitz Neuromuscular Centre, Institute of Child Health
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Institute of Genetic Medicine,Muscle Team
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Clinical Research Facility
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Royal Victoria Infirmary Research Pharmacy
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Wagner KR, Abdel-Hamid HZ, Mah JK, Campbell C, Guglieri M, Muntoni F, Takeshima Y, McDonald CM, Kostera-Pruszczyk A, Karachunski P, Butterfield RJ, Mercuri E, Fiorillo C, Bertini ES, Tian C, Statland J, Sadosky AB, Purohit VS, Sherlock SP, Palmer JP, Binks M, Charnas L, Marraffino S, Wong BL. Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. Neuromuscul Disord. 2020 Jun;30(6):492-502. doi: 10.1016/j.nmd.2020.05.002. Epub 2020 May 19.