A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Duchenne Muscular Dystrophy

NCT02310763 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: B51610022014-002072-92
• Study Type: interventional
• Target: 121
• Locations: 8 countries
• Sites: 66

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).

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne Muscular Dystrophy, myostatin

Outcome Measures

Primary Outcomes (22)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49

  An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator.

  Study Day 1 to Week 49 visit

• Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49

  An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.

  Study Day 1 to Week 49 visit

• Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49

  An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.

  Study Day 1 to Week 49 visit

• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology

  Hematology evaluation included: hemoglobin, hematocrit, red blood cell (RBC) count, platelets, RBC morphology, white blood cell (WBC) count, absolute lymphocytes, absolute atypical lymphocytes, absolute total neutrophils, absolute total neutrophils count, absolute band cells, absolute basophils, absolute eosinophils, absolute monocytes and absolute myelocytes.

  Baseline to Week 49 visit

• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation

  Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT).

  Baseline to Week 49 visit

• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function

  Liver function evaluation included: total/direct/indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase.

  Baseline to Week 49 visit

• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function

  Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid.

  Baseline to Week 49 visit

• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes

  Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate, bicarbonate, ferritin, transferrin saturation, iron, iron binding capacity and unsaturated iron binding capacity. Number of participants with iron abnormalities was reported in different age groups.

  Baseline to Week 49 visit

• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones

  Hormone evaluations included free thyroxine (T4), thyroid stimulating hormone (TSH), lutenizing hormone (LH), follicle stimulating hormone (FSH), and androstenedione. Numbers of participants with abnormalities of LH, FSH and androstenedione were reported in different age groups.

  Baseline to Week 49 visit

• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry

  Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, and amylase.

  Baseline to Week 49 visit

• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis

  Urinalysis included: urine pH, qualitative urine glucose, qualitative urine ketones, qualitative urine protein, qualitative blood/hemoglobin, urine nitrite, urine leukocytes, urine RBC, urine WBC, urine granular casts, urine hyaline casts, urine urate (uric acid) acidic crystal, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam.

  Baseline to Week 49 visit

• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal

  Number of participants with blood detected in fecal samples is presented.

  Baseline to Week 49 visit

• Categorical Summary of Liver Iron Accumulation by Week 49

  Magnetic resonance imaging (MRI) of Liver was obtained to quantify liver iron accumulation for safety monitoring. MRIs were sent to an independent central radiology imaging facility for calculation of the average transverse relaxation rate (R2\*) value which was used to monitor for iron accumulation in the liver. Number of participants meeting the following criteria is presented as follows: 1) normal: R2\*\<=75Hz at 1.5T or \<=139 Hz at 3.0T; 2) above normal: R2\*\>75Hz and \<=190Hz at 1.5T or R2\* \>139Hz and \<=369Hz at 3.0T; 3) mild overload: R2\*\>190Hz at 1.5T or R2\*\>360Hz at 3.0T.

  Screening, Weeks 13, 29 and 45

• Number of Participants With Physical Examination Findings Reported as SAEs by Week 49

  Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. A targeted nose and throat mucosal exam were also performed to monitor for any signs of mucosal telangiectasias. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which physical examination findings were reported as SAEs.

  Baseline to Week 49 visit

• Summary of Tanner Stage Rating by Week 49

  Tanner staging was performed before the first dose of each dose escalation to monitor for signs of accelerated sexual development. The physical changes in pubertal development (pubic hair, penis and testes) were assessed using the system described by Marshall and Tanner. Stage 1 is preadolescent, Stages 2, 3, and 4 are initiation of puberty and Stage 5 is mature adult. Details about the system can be referred to Tanner JM. Growth at Adolescence. Blackwell Scientific Publications 1962; 2nd edition.

  Baseline, Weeks 17, 33 and 49

• Number of Participants With Vital Signs Findings Reported as SAEs by Week 49

  Vital signs evaluation included supine systolic and diastolic blood pressure (BP), pulse rate, and respiratory rate. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which vital signs findings were reported as SAEs.

  Baseline to Week 49 visit

• Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49

  Number of participants with ECG data meeting the following criteria are presented: 1) corrected QT interval using Fridericia's formula (QTcF interval) \<450msec; 2) QTcF interval \>=450 and \<480msec; 3) QTcF interval \>=480 and \<500msec; 4) QTcF interval\>=500msec; 5) QTcF interval increase from baseline\<30msec; 6) QTcF interval increase from baseline \>=30 and \<60msec; 7) QTcF interval increase from baseline \>=60msec.

  Baseline to Week 49 visit

• Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Compared to Placebo by Week 49

  The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance image (MRI) or echocardiogram. The same method of cardiac imaging was used consistently within a single participant. Cardiac MRIs were read by a central imaging vendor and echocardiograms were read locally at each site. The LVEF values measured by cardiac MRI and echocardiogram are combined in the following presentation. The analysis of covariance (ANCOVA) model was used to analyze the change from baseline for domagrozumab compared to placebo on LVEF. The baseline result, age, use of angiotensin receptor blocker (ARB)/beta blocker/angiotensin converting enzyme (ACE) inhibitor and treatment were included as fixed effects in the model.

  Baseline to Week 49 visit

• Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49

  Bone mineral density (BMD) was evaluated by Dual energy X-ray Absorptiometry (DXA). The height adjusted Z-score presented below is the number of standard deviations which compares the BMD of the participant to the average BMD matched for their age, sex and ethnicity. If the Z-score was -2 standard deviations or lower, the result was "below the expected range for age". If the Z-score was above -2 standard deviations, the result was "within the expected range for age".

  Screening and Week 49

• Bone Age to Chronological Age Ratio by Week 49

  Bone age assessment was evaluated by the ratio of the bone age to the chronological age using the X rays of the hand and wrist. Ratio of bone age to chronological age was calculated by bone age/chronological age at scan date. Chronological age at scan date was calculated by (scan date-date of birth+1)/365.25.

  Screening, Weeks 17, 33 and 49

• Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49

  An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. The Columbia Suicide Severity Rating Scale (C-SSRS) was performed to identify the risk of suicide ideation or behavior. AEs of suicide ideation or behavior were determined by the investigator.

  Baseline to Week 49 visit

• Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49

  The 4SC quantified the time required for a participant to ascend 4 standard steps. Mixed effect model for repeated measures (MMRM) was used to analyze the change from baseline on 4SC for domagrozumab compared to placebo. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

  Baseline, Weeks 17, 33 and 49

Secondary Outcomes (52)

• Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49

  Baseline, Weeks 17, 33 and 49

• Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49

  Baseline, Weeks 17, 33 and 49

• Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49

  Baseline, Weeks 17, 33 and 49

• Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49

  Baseline, Weeks 17, 33 and 49

• Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49

  Baseline, Weeks 17, 33 and 49

Other Outcomes (1)

• Area Under the Curve From Time Zero to Last Quantifiable Serum Concentration (AUClast) of Domagrozumab

  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

Study Arms (2)

PF-06252616

EXPERIMENTAL

3 dose levels (5mg/kg, 20mg/kg and 40 mg/kg) of IV infused PF-06252616 will be investigated within each subject

Biological: PF-06252616

Placebo

PLACEBO COMPARATOR

Matching Placebo

Drug: Placebo

Interventions

PF-06252616 BIOLOGICAL

PF-06252616 IV Infusion, 3 dose levels (5mg/kg, 20 mg/kg and 40 mg/kg) will be investigated within each subject

PF-06252616

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 6 Years - 15 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).
• Subjects who are able to perform the 4 stair climb in \> or = 0.33 but \< or =1.6 stairs/second.
• 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.
• Adequate hepatic and renal function on screening laboratory assessments.
• No underlying disposition for iron accumulation on screening laboratory assessments.
• Iron content estimate on the screening liver MRI is within the normal range.

You may not qualify if:

• Subjects with known cognitive impairment or behavioral issues that would impede the ability to follow instructions.
• History of major surgical procedure within 6 weeks of signing the informed consent or planned surgery during the study.
• 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.
• Presence or history of other musculoskeletal or neurologic disease or somatic disorder not related to DMD including pulmonary and cardiac disease.
• 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.
• 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).
• Documented history of iron overload including hemochromatosis, beta thalassemia major, beta thalassemia intermedia or hemolytic anemia.
• Unwilling or unable (eg, metal implants, requires sedation) to undergo examination with closed MRI without sedation.
• 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.
• 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.
• Current or prior treatment within the past 3 months with androgens or human growth hormone.
• 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).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (66)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Ronald Reagan UCLA Pharmacy

Los Angeles, California, 90095, United States

Location

UCLA (David Geffen School of Medicine)

Los Angeles, California, 90095, United States

Location

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Shriners Hospitals for Children - Tampa

Tampa, Florida, 33612, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Iowa ICTS

Iowa City, Iowa, 52242, United States

Location

KU Clinical Research Center, Clinical and Translational Science Unit(CTSU)

Fairway, Kansas, 66205, United States

Location

University of Kansas-Clinical Research Center, Investigational Pharmacy

Fairway, Kansas, 66205, United States

Location

University of Kansas Medical Center, Landon Center on Aging

Kansas City, Kansas, 66160, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Kennedy Krieger Institute Out-patient center

Baltimore, Maryland, 21205, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Johns Hopkins Investigational Drug Service

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Minnesota Masonic Children's Hospital

Minneapolis, Minnesota, 55455, United States

Location

St Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center,Lenox Baker Children's Hospital

Durham, North Carolina, 27705, United States

Location

Duke University, Investigational Drug Pharmacy

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Center for Clinical and Translational Sciences

Salt Lake City, Utah, 84108, United States

Location

Utah Center for Advanced Imaging and Research (UCAIR)

Salt Lake City, Utah, 84108, United States

Location

Investigational Drug Services

Salt Lake City, Utah, 84112, United States

Location

University of Utah, Department of Neurology

Salt Lake City, Utah, 84112, United States

Location

University of Utah Medical Center

Salt Lake City, Utah, 84132, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

Lady Cilento Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

Clinical Densitometry and Bone Metabolic Disease Department, General and Clinical Pathology Clinic

Sofia, 1431, Bulgaria

Location

Hospital Pharmacy, UMHAT Alexandrovska

Sofia, 1431, Bulgaria

Location

Imaging Diagnostic Clinic,UMHAT Alexandrovska

Sofia, 1431, Bulgaria

Location

Neurology Disease Clinic,UMHAT Alexandrovska

Sofia, 1431, Bulgaria

Location

UMHAT Alexandrovska Cardiology Department,Internal Diseases Propaedeutic Clinic

Sofia, 1431, Bulgaria

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

UBC Children's and Women's Health Center of British Columbia

Vancouver, British Columbia, V6H3V4, Canada

Location

Children's Hospital- London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

UOC Farmacia-Istituto Gianna Gaslini, Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico

Genova, 16147, Italy

Location

UOC Medicina Fisica Riabilitativa

Genova, 16147, Italy

Location

UOC Neurologia Pediatrica e Malattie Muscolari

Genova, 16147, Italy

Location

UOC Radiologia-Istituto Gianna. Gaslini, Istituto Pediatrico di Ricovero e Cura a Carattere

Genova, 16147, Italy

Location

UOS Dipartimentale Endocrinologia Clinica Sperimentale

Genova, 16147, Italy

Location

Dipartimento Pediatrico Universitario-Ospedaliero Endocrinologia

Rome, 00150, Italy

Location

Farmacia Ospedaliera, IRCCS Ospedale Pediatrico Bambino Gesù, Padiglione Sant'Onofrio

Rome, 00165, Italy

Location

Malattie Neuromuscolari e Neurodegenerative, IRCCS Ospedale Pediatrico Bambino Gesù

Rome, 00165, Italy

Location

Ospedale Pediatrico Bambino Gesù - Centro Trial, DPUO - Padiglione Salviati

Rome, 00165, Italy

Location

U.O.C Farmacia

Rome, 00168, Italy

Location

U.O.C. Neuropsichiatria Infantile, Fondazione Policlinico

Rome, 00168, Italy

Location

Hyogo college of medicine hospital

Hyōgo, 663-8501, Japan

Location

National Center of Neurology and Psychiatry

Tokyo, 187-8551, Japan

Location

Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie Apteka Szpitalna Blok F

Warsaw, 02-097, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, I Katedra i Klinika Kardiologii

Warsaw, 02-097, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, II Zaklad Radiologii Klinicznej

Warsaw, 02-097, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, Klinika Neurologii

Warsaw, 02-097, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, Laboratorium Centralne

Warsaw, 02-097, Poland

Location

MTZ Clinical Research Sp.z o.o.

Warsaw, 02-106, Poland

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, L12 2AP, United Kingdom

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, L14 5AB, United Kingdom

Location

Dubowitz Neuromuscular Centre Institute of Child Health

London, WC1N 3JH, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

Institute of Genetic Medicine, Muscle Team

Newcastle upon Tyne, NE1 3BZ, United Kingdom

Location

Clinical Research Facility

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Royal Victoria Infirmary Research Pharmacy

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (8)

• Sherlock SP, McCrady A, Palmer J, Aghamolaey H, Ahlgren A, Widholm P, Dahlqvist Leinhard O, Karlsson M. Relationship Between Quantitative Magnetic Resonance Imaging Measures and Functional Changes in Patients With Duchenne Muscular Dystrophy. Muscle Nerve. 2025 Mar;71(3):343-352. doi: 10.1002/mus.28321. Epub 2024 Dec 23.

  PMID: 39713935 DERIVED

• 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.

  PMID: 36335191 DERIVED

• 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.

  PMID: 36104012 DERIVED

• 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.

  PMID: 35998119 DERIVED

• 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.

  PMID: 35396602 DERIVED

• 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.

  PMID: 34533053 DERIVED

• 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.

  PMID: 34155911 DERIVED

• 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.

  PMID: 32522498 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

domagrozumab

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

This study was terminated because the primary efficacy objective (the efficacy of treatment with domagrozumab based on a mean change from baseline on 4 Stair Climb as compared to placebo following 48 weeks of treatment) was not met.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: December 8, 2014
• Study Start: November 24, 2014
• Primary Completion: April 30, 2018
• Study Completion: November 23, 2018
• Last Updated: December 7, 2020
• Results First Posted: July 23, 2019

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share

Locations

CA (4); GB (7); JP (2); AU (1); IT (11); US (30); PL (6); BU (5)