Clinical trial NCT02310763: A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Duchenne Muscular Dystrophy
Official title: A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTIPLE ASCENDING DOSE STUDY TO EVALUATE THE SAFETY, EFFICACY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF-06252616 IN AMBULATORY BOYS WITH DUCHENNE MUSCULAR DYSTROPHY
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne Muscular Dystrophy, myostatin
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-12-08
Enrollment: 121
Sex: MALE
Minimum age (years): 6
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: This is a Phase 2 randomized, 2-period, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, efficacy, PK and PD of PF-06252616 administered to ambulatory boys diagnosed with Duchenne Muscular Dystrophy. Three intravenous (IV) dose levels will be investigated in a within subject dose escalating fashion. Subjects will be randomly assigned to 1 of 3 sequence groups for approximately 96 weeks (2 periods of 48 weeks each). In period 1, two of the sequence groups will receive PF-06252616 and one sequence group will receive placebo. In period 2, the placebo group will switch to PF-06252616 and the two remaining sequence groups will either receive placebo or PF-06252616. Efficacy will be based on an observed mean change from baseline on function (4 stair climb) of PF-06252616 as compared to the placebo at the end of period 1. Period 2 provides an opportunity to evaluate PK. Subjects will receive monthly IV infused doses of either PF-06252616 or placebo and will undergo safety evaluations (Laboratory, cardiac monitoring, physical exams, x-ray, MRI), functional evaluations (pulmonary function testing, 4 stair climb, range of motion, strength testing, Northstar Ambulatory Assessment, upper limb functional testing and the six minute walk test), pharmacokinetic testing and pharmacodynamic testing to evaluate changes in muscle volume (MRI).


Eligibility criteria: Inclusion Criteria:

1. Ambulatory boys age 6 to \<16 years old (at the time of randomization), diagnosed with DMD. Diagnosis must be confirmed in subject's medical history and by genetic testing obtained during routine clinical care for diagnostic purposes as reported from an appropriate regulated laboratory using a clinically validated genetic test (genetic testing is not provided by the sponsor).
2. Subjects who are able to perform the 4 stair climb in \> or = 0.33 but \< or =1.6 stairs/second.
3. Subjects must be receiving glucocorticosteroids for a minimum of 6 months prior to signing informed consent. There should be no significant change (\>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.
4. Adequate hepatic and renal function on screening laboratory assessments.
5. No underlying disposition for iron accumulation on screening laboratory assessments.
6. Iron content estimate on the screening liver MRI is within the normal range.

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 or beta blockers, ARB (angiotensin II receptor antagonist) 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 ot 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).

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49
timeFrame: Study Day 1 to Week 49 visit
measure: Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49
timeFrame: Study Day 1 to Week 49 visit
measure: Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49
timeFrame: Study Day 1 to Week 49 visit
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology
timeFrame: Baseline to Week 49 visit
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation
timeFrame: Baseline to Week 49 visit
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function
timeFrame: Baseline to Week 49 visit
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function
timeFrame: Baseline to Week 49 visit
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes
timeFrame: Baseline to Week 49 visit
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones
timeFrame: Baseline to Week 49 visit
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry
timeFrame: Baseline to Week 49 visit
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis
timeFrame: Baseline to Week 49 visit
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal
timeFrame: Baseline to Week 49 visit
measure: Categorical Summary of Liver Iron Accumulation by Week 49
timeFrame: Screening, Weeks 13, 29 and 45
measure: Number of Participants With Physical Examination Findings Reported as SAEs by Week 49
timeFrame: Baseline to Week 49 visit
measure: Summary of Tanner Stage Rating by Week 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Number of Participants With Vital Signs Findings Reported as SAEs by Week 49
timeFrame: Baseline to Week 49 visit
measure: Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49
timeFrame: Baseline to Week 49 visit
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Compared to Placebo by Week 49
timeFrame: Baseline to Week 49 visit
measure: Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49
timeFrame: Screening and Week 49
measure: Bone Age to Chronological Age Ratio by Week 49
timeFrame: Screening, Weeks 17, 33 and 49
measure: Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49
timeFrame: Baseline to Week 49 visit
measure: Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
Secondary outcomes:
measure: Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline to Week 49 on 4SC for Participants in Sequence 3 Compared to the Natural History Control Group
timeFrame: Baseline, Week 49
measure: Change From Baseline to Week 97 on 4SC for Participants in Sequence 1 Compared to the Natural History Control Group
timeFrame: Baseline, Week 97
measure: Change From Baseline to Week 49 on FVC for Participants in Sequence 3 Compared to the Natural History Control Group
timeFrame: Baseline, Week 49
measure: Change From Baseline to Week 97 on FVC for Participants in Sequence 1 Compared to the Natural History Control Group
timeFrame: Baseline, Week 97
measure: Change From Baseline to Week 49 on NSAA for Participants in Sequence 3 Compared to the Natural History Control Group
timeFrame: Baseline, Week 49
measure: Change From Baseline to Week 97 on NSAA for Participants in Sequence 1 Compared to the Natural History Control Group
timeFrame: Baseline, Week 97
measure: Change From Baseline to Week 49 on 6MWD for Participants in Sequence 3 Compared to the Natural History Control Group
timeFrame: Baseline, Week 49
measure: Change From Baseline to Week 97 on 6MWD for Participants in Sequence 1 Compared to the Natural History Control Group
timeFrame: Baseline, Week 97
measure: Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets
timeFrame: Baseline, Week 17
measure: Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets
timeFrame: Baseline, Week 33
measure: Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets
timeFrame: Baseline, Week 49
measure: Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets
timeFrame: Baseline, Week 17
measure: Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets
timeFrame: Baseline, Week 33
measure: Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets
timeFrame: Baseline, Week 49
measure: Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets
timeFrame: Baseline, Week 17
measure: Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets
timeFrame: Baseline, Week 33
measure: Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets
timeFrame: Baseline, Week 49
measure: Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets
timeFrame: Baseline, Week 17
measure: Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets
timeFrame: Baseline, Week 33
measure: Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets
timeFrame: Baseline, Week 49
measure: Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets
timeFrame: Baseline, Week 17
measure: Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets
timeFrame: Baseline, Week 33
measure: Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets
timeFrame: Baseline, Week 49
measure: Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds)
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds)
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds)
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49
timeFrame: Baseline, Weeks 17, 33 and 49
measure: Change From Baseline in Whole Thigh Muscle Volume Through Week 97
timeFrame: Baseline, Weeks 17, 33, 49 and 97
measure: Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97
timeFrame: Baseline, Weeks 17, 33, 49 and 97
measure: Concentration of Growth Differentiation Factor 8 (GDF-8) at Time 0 (Pre-dose),(C0(GDF-8) )
timeFrame: Predose on Day 1 of Week 1
measure: Trough Serum Concentration of GDF-8 (Ctrough,(GDF-8)) for Participants Receiving Domagrozumab in Period 1
timeFrame: Every 4 weeks on dosing day (at predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 48
measure: Ctrough,(GDF-8) for Participants of Sequence 3 in Period 2
timeFrame: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 49 to Week 96
measure: Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab
timeFrame: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3
measure: Maximum Serum Concentration (Cmax) of Domagrozumab
timeFrame: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3
measure: Time for Cmax (Tmax) of Domagrozumab
timeFrame: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3
measure: Terminal Half-life (t1/2) of Domagrozumab for Participants in Sequence 2 After the Last Dose of Domagrozumab
timeFrame: At predose, end of 2-hour infusion and 6 hours since start of infusion at Week 45
measure: Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab
timeFrame: At predose, end of 2-hour infusion,6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45
measure: Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab
timeFrame: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45
measure: Clearance (CL) of Domagrozumab
timeFrame: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 13, 29 and 45
measure: Volume of Distribution at Steady State (Vss) of Domagrozumab for Participants in Sequence 2 Required for Additional PK Assessment
timeFrame: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Week 45
measure: Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97
timeFrame: Baseline, every 4 weeks from Week 5 to Week 97 visit or early termination
Other outcomes:
measure: Area Under the Curve From Time Zero to Last Quantifiable Serum Concentration (AUClast) of Domagrozumab
timeFrame: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45
Locations:
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)
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Tampa
country: United States
facility: Shriners Hospitals for Children - Tampa
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa ICTS
state: Iowa
city: Fairway
country: United States
facility: KU Clinical Research Center, Clinical and Translational Science Unit(CTSU)
state: Kansas
city: Fairway
country: United States
facility: University of Kansas-Clinical Research Center, Investigational Pharmacy
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Medical Center, Landon Center on Aging
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
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: Saint Louis
country: United States
facility: St Louis Children'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: The 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: University of Utah, Department of Neurology
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah School of Medicine
state: Utah
city: South Brisbane
country: Australia
facility: Lady Cilento Children's Hospital
state: Queensland
city: Sofia
country: Bulgaria
facility: Clinical Densitometry and Bone Metabolic Disease Department, General and Clinical Pathology Clinic
city: Sofia
country: Bulgaria
facility: Hospital Pharmacy, UMHAT Alexandrovska
city: Sofia
country: Bulgaria
facility: Imaging Diagnostic Clinic,UMHAT Alexandrovska
city: Sofia
country: Bulgaria
facility: Neurology Disease Clinic,UMHAT Alexandrovska
city: Sofia
country: Bulgaria
facility: UMHAT Alexandrovska Cardiology Department,Internal Diseases Propaedeutic Clinic
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: UBC Children's and Women's Health Center 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: CHU Sainte-Justine
state: Quebec
city: Genova
country: Italy
facility: UOC Farmacia-Istituto Gianna Gaslini, Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico
city: Genova
country: Italy
facility: UOC Medicina Fisica Riabilitativa
city: Genova
country: Italy
facility: UOC Neurologia Pediatrica e Malattie Muscolari
city: Genova
country: Italy
facility: UOC Radiologia-Istituto Gianna. Gaslini, Istituto Pediatrico di Ricovero e Cura a Carattere
city: Genova
country: Italy
facility: UOS Dipartimentale Endocrinologia Clinica Sperimentale
city: Rome
country: Italy
facility: Dipartimento Pediatrico Universitario-Ospedaliero Endocrinologia
city: Rome
country: Italy
facility: Farmacia Ospedaliera, IRCCS Ospedale Pediatrico Bambino Gesù, Padiglione Sant'Onofrio
city: Rome
country: Italy
facility: Malattie Neuromuscolari e Neurodegenerative, IRCCS Ospedale Pediatrico Bambino Gesù
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesù - Centro Trial, DPUO - Padiglione Salviati
city: Rome
country: Italy
facility: U.O.C Farmacia
city: Rome
country: Italy
facility: U.O.C. Neuropsichiatria Infantile, Fondazione Policlinico
city: Hyogo
country: Japan
facility: Hyogo college of medicine hospital
city: Tokyo
country: Japan
facility: National Center of Neurology and Psychiatry
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie Apteka Szpitalna Blok F
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, I Katedra i Klinika Kardiologii
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, II Zaklad Radiologii Klinicznej
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, Klinika Neurologii
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, Laboratorium Centralne
city: Warszawa
country: Poland
facility: MTZ Clinical Research Sp.z o.o.
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's NHS Foundation Trust
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's NHS Foundation Trust
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: Royal Victoria Infirmary Research Pharmacy
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Clinical Research Facility
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Sherlock SP, Palmer J, Wagner KR, Abdel-Hamid HZ, Tian C, Mah JK, Muntoni F, Guglieri M, Butterfield RJ, Charnas L, Marraffino S. Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy. Sci Rep. 2022 Nov 5;12(1):18762. doi: 10.1038/s41598-022-23072-5.
citation: Wojciechowski J, Purohit VS, Harnisch LO, Dua P, Tan B, Nicholas T. Population PK and PD Analysis of Domagrozumab in Pediatric Patients with Duchenne Muscular Dystrophy. Clin Pharmacol Ther. 2022 Dec;112(6):1291-1302. doi: 10.1002/cpt.2747. Epub 2022 Oct 4.
citation: Muntoni F, Guglieri M, Mah JK, Wagner KR, Brandsema JF, Butterfield RJ, McDonald CM, Mayhew AG, Palmer JP, Marraffino S, Charnas L, Mercuri E. Novel approaches to analysis of the North Star Ambulatory Assessment (NSAA) in Duchenne muscular dystrophy (DMD): Observations from a phase 2 trial. PLoS One. 2022 Aug 23;17(8):e0272858. doi: 10.1371/journal.pone.0272858. eCollection 2022.
citation: Sherlock SP, Palmer J, Wagner KR, Abdel-Hamid HZ, Bertini E, Tian C, Mah JK, Kostera-Pruszczyk A, Muntoni F, Guglieri M, Brandsema JF, Mercuri E, Butterfield RJ, McDonald CM, Charnas L, Marraffino S. Quantitative magnetic resonance imaging measures as biomarkers of disease progression in boys with Duchenne muscular dystrophy: a phase 2 trial of domagrozumab. J Neurol. 2022 Aug;269(8):4421-4435. doi: 10.1007/s00415-022-11084-0. Epub 2022 Apr 8.
citation: Wagner KR, Guglieri M, Ramaiah SK, Charnas L, Marraffino S, Binks M, Vaidya VS, Palmer J, Goldstein R, Muntoni F. Safety and disease monitoring biomarkers in Duchenne muscular dystrophy: results from a Phase II trial. Biomark Med. 2021 Oct;15(15):1389-1396. doi: 10.2217/bmm-2021-0222. Epub 2021 Sep 17.
citation: Sherlock SP, Zhang Y, Binks M, Marraffino S. Quantitative muscle MRI biomarkers in Duchenne muscular dystrophy: cross-sectional correlations with age and functional tests. Biomark Med. 2021 Jun;15(10):761-773. doi: 10.2217/bmm-2020-0801. Epub 2021 Jun 22.
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.