NCT02310763

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

Terminated Phase 2 Results posted Last updated 7 December 2020

What this trial tests

Phase 2 trial testing PF-06252616 in Duchenne Muscular Dystrophy in 121 participants. Terminated before completion.

Timeline

24 November 2014

Primary endpoint
30 April 2018

23 November 2018

Quick facts

Lead sponsor	Pfizer
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Masking	quadruple
Primary purpose	treatment
Enrollment	121
Start date	24 November 2014
Primary completion	30 April 2018
Estimated completion	23 November 2018
Sites	66 locations across Italy, Japan, United Kingdom, Poland, Canada, Bulgaria, Australia, United States

Drugs / interventions tested

• PF-06252616 — full drug profile →
• Placebo

Conditions studied

• Duchenne Muscular Dystrophy — all drugs for Duchenne Muscular Dystrophy →

Sponsor

Pfizer — full company profile →

Who can join

Adults 6 to 15, male only, with Duchenne Muscular Dystrophy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 Primary · Study Day 1 to Week 49 visit

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

All-causalities TEAE

Group	Value	95% CI
Placebo	38
Domagrozumab 5 mg/kg	66
Domagrozumab 20 mg/kg	57
Domagrozumab 40 mg/kg	59

Treatment-related TEAE

Group	Value	95% CI
Placebo	14
Domagrozumab 5 mg/kg	18
Domagrozumab 20 mg/kg	14
Domagrozumab 40 mg/kg	16

All-causalities serious TEAE

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	1
Domagrozumab 20 mg/kg	1
Domagrozumab 40 mg/kg	1

Treatment-related serious TEAE

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	1

All-causalities severe TEAE

Group	Value	95% CI
Placebo	2
Domagrozumab 5 mg/kg	2
Domagrozumab 20 mg/kg	3
Domagrozumab 40 mg/kg	2

Treatment-related severe TEAE

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	1

Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 Primary · Study Day 1 to Week 49 visit

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.

All-causalities TEAE

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	1

Treatment-related TEAE

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	1

Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 Primary · Study Day 1 to Week 49 visit

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.

All-causalities TEAE

Group	Value	95% CI
Placebo	8
Domagrozumab 5 mg/kg	4
Domagrozumab 20 mg/kg	4
Domagrozumab 40 mg/kg	0

Treatment-related TEAE

Group	Value	95% CI
Placebo	3
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	1
Domagrozumab 40 mg/kg	0

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

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.

Hemoglobin <0.8*lower limit of normal (LLN)

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Hematocrit <0.8*LLN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

RBC count <0.8*LLN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Platelets <0.5*LLN

Group	Value	95% CI
Placebo	1
Domagrozumab 5 mg/kg	1
Domagrozumab 20 mg/kg	1
Domagrozumab 40 mg/kg	1

Platelets >1.75*upper limit of normal (ULN)

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

RBC Morphology >0

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	1
Domagrozumab 40 mg/kg	1

WBC count <0.6*LLN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

WBC count >1.5*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	1
Domagrozumab 20 mg/kg	1
Domagrozumab 40 mg/kg	0

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

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

aPTT >1.1*ULN

Group	Value	95% CI
Placebo	1
Domagrozumab 5 mg/kg	1
Domagrozumab 20 mg/kg	1
Domagrozumab 40 mg/kg	2

PT >1.1*ULN

Group	Value	95% CI
Placebo	13
Domagrozumab 5 mg/kg	6
Domagrozumab 20 mg/kg	3
Domagrozumab 40 mg/kg	7

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

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.

Total bilirubin >1.5*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Direct bilirubin >1.5*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 40 mg/kg	0

Indirect bilirubin >1.5*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 40 mg/kg	0

AST >3*ULN

Group	Value	95% CI
Placebo	39
Domagrozumab 5 mg/kg	80
Domagrozumab 20 mg/kg	76
Domagrozumab 40 mg/kg	74

ALT >3*ULN

Group	Value	95% CI
Placebo	40
Domagrozumab 5 mg/kg	80
Domagrozumab 20 mg/kg	78
Domagrozumab 40 mg/kg	75

GGT >3*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Alkaline phosphatase >3*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Total protein <0.8*LLN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

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

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

BUN >1.3*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Creatinine >1.3*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Uric acid >1.2*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	1
Domagrozumab 20 mg/kg	3
Domagrozumab 40 mg/kg	3

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

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.

Sodium <0.95*LLN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Sodium >1.05*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Potassium <0.9*LLN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Potassium >1.1*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Chloride <0.9*LLN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Chloride >1.1*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Calcium <0.9*LLN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Calcium >1.1*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

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

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.

Free T4 <0.8*LLN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Free T4 >1.2*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

TSH <0.8*LLN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	2
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	1

TSH >1.2*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

LH (15 Days<=Age<7 Years) <0.3 (mIU/mL)

Group	Value	95% CI
Placebo	1
Domagrozumab 5 mg/kg	2
Domagrozumab 20 mg/kg	0

LH (15 Days<=Age<7 Years) >2.8 (mIU/mL)

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0

LH (7 Years<=Age<9 Years) <0.3 (mIU/mL)

Group	Value	95% CI
Placebo	6
Domagrozumab 5 mg/kg	23
Domagrozumab 20 mg/kg	21
Domagrozumab 40 mg/kg	14

LH (7 Years<=Age<9 Years) >2.8 (mIU/mL)

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

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

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

Glucose <0.6*LLN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Glucose >1.5*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	1
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	2

CK >2.0*ULN

Group	Value	95% CI
Placebo	40
Domagrozumab 5 mg/kg	80
Domagrozumab 20 mg/kg	78
Domagrozumab 40 mg/kg	76

Troponin I >3.0*ULN

Group	Value	95% CI
Placebo	11
Domagrozumab 5 mg/kg	12
Domagrozumab 20 mg/kg	10
Domagrozumab 40 mg/kg	13

Amylase >1.5*ULN

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	1

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

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.

Qualitative urine glucose (dipstick) >=1

Group	Value	95% CI
Placebo	1
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Qualitative urine ketones(dipstick) >=1

Group	Value	95% CI
Placebo	3
Domagrozumab 5 mg/kg	3
Domagrozumab 20 mg/kg	5
Domagrozumab 40 mg/kg	6

Qualitative urine protein (dipstick) >=1

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	1
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Qualitative urine blood/hemoglobin (dipstick) >=1

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	2
Domagrozumab 20 mg/kg	1
Domagrozumab 40 mg/kg	0

Urine nitrite (dipstick) >=1

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Urine leukocytes (dipstick): +1

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	1
Domagrozumab 40 mg/kg	1

Urine RBC >=20 (/high power field[HPF])

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

Urine WBC >=20 (/HPF)

Group	Value	95% CI
Placebo	0
Domagrozumab 5 mg/kg	0
Domagrozumab 20 mg/kg	0
Domagrozumab 40 mg/kg	0

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

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

Group	Value	95% CI
Placebo	2
Domagrozumab 5 mg/kg	8
Domagrozumab 20 mg/kg	2
Domagrozumab 40 mg/kg	3

Adverse events — posted to ClinicalTrials.gov

Time frame: 105 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Domagrozumab 5 mg/kg, Period 1

Serious: 1/80 (1%)

Deaths: 0/80

Domagrozumab 20 mg/kg, Period 1

Serious: 1/78 (1%)

Deaths: 0/78

Domagrozumab 40 mg/kg, Period 1

Serious: 1/76 (1%)

Deaths: 0/76

Placebo, Period 1

Serious: 0/40 (0%)

Deaths: 0/40

Domagrozumab 5 mg/kg, Period 2

Serious: 1/38 (3%)

Deaths: 0/38

Domagrozumab 20 mg/kg, Period 2

Serious: 1/38 (3%)

Deaths: 0/38

Domagrozumab 40 mg/kg, Period 2

Serious: 1/66 (2%)

Deaths: 0/66

Placebo, Period 2

Serious: 0/37 (0%)

Deaths: 0/37

Serious adverse events (6 terms)

Reaction	System	Domagrozumab 5 mg/kg, Peri…	Domagrozumab 20 mg/kg, Per…	Domagrozumab 40 mg/kg, Per…	Placebo, Period 1	Domagrozumab 5 mg/kg, Peri…	Domagrozumab 20 mg/kg, Per…	Domagrozumab 40 mg/kg, Per…	Placebo, Period 2
Appendicitis	Infections and infestations	—	—	—	—	—	—	—	—
Femoral neck fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Troponin increased	Investigations	—	—	—	—	—	—	—	—
Superior sagittal sinus thrombosis	Nervous system disorders	—	—	—	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—	—	—	—

Other adverse events (40 terms — click to expand)

Reaction	System	Domagrozumab 5 mg/kg, Peri…	Domagrozumab 20 mg/kg, Per…	Domagrozumab 40 mg/kg, Per…	Placebo, Period 1	Domagrozumab 5 mg/kg, Peri…	Domagrozumab 20 mg/kg, Per…	Domagrozumab 40 mg/kg, Per…	Placebo, Period 2
Fall	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—
Upper resiratory tract infection	Infections and infestations	—	—	—	—	—	—	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Gait inability	General disorders	—	—	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Ear infection	Infections and infestations	—	—	—	—	—	—	—	—
Ligment sprain	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Spinal compression fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—
Infusion site swelling	General disorders	—	—	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Pain	General disorders	—	—	—	—	—	—	—	—
Hordeolum	Infections and infestations	—	—	—	—	—	—	—	—
Lower respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—	—
Scoliosis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Tendon disorder	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Dermatitis contact	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Erythema	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—

Most-reported serious reactions: Appendicitis, Femoral neck fracture, Femur fracture, Troponin increased, Superior sagittal sinus thrombosis, Anxiety.

Data from ClinicalTrials.gov NCT02310763 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Viral vector platforms within the gene therapy landscape.
   Bulcha JT, Wang Y, Ma H, Tai PWL, et al · · 2021 · cited 899× · PMID 33558455 · DOI 10.1038/s41392-021-00487-6
2. Sarcopenia and Muscle Aging: A Brief Overview.
   Dao T, Green AE, Kim YA, Bae SJ, et al · · 2020 · cited 156× · PMID 33397034 · DOI 10.3803/enm.2020.405
3. Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine.
   Chaytow H, Faller KME, Huang YT, Gillingwater TH. · · 2021 · cited 103× · PMID 34337562 · DOI 10.1016/j.xcrm.2021.100346
4. A mouse anti-myostatin antibody increases muscle mass and improves muscle strength and contractility in the mdx mouse model of Duchenne muscular dystrophy and its humanized equivalent, domagrozumab (PF-06252616), increases muscle volume in cynomolgus monkeys.
   St Andre M, Johnson M, Bansal PN, Wellen J, et al · · 2017 · cited 78× · PMID 29121992 · DOI 10.1186/s13395-017-0141-y
5. Myostatin/Activin Receptor Ligands in Muscle and the Development Status of Attenuating Drugs.
   Rodgers BD, Ward CW. · · 2022 · cited 68× · PMID 34520530 · DOI 10.1210/endrev/bnab030
6. Recent advances in innovative therapeutic approaches for Duchenne muscular dystrophy: from discovery to clinical trials.
   Shimizu-Motohashi Y, Miyatake S, Komaki H, Takeda S, et al · · 2016 · cited 68× · PMID 27398133
7. Myostatin inhibition in combination with antisense oligonucleotide therapy improves outcomes in spinal muscular atrophy.
   Zhou H, Meng J, Malerba A, Catapano F, et al · · 2020 · cited 60× · PMID 32031328 · DOI 10.1002/jcsm.12542
8. Drug development progress in duchenne muscular dystrophy.
   Deng J, Zhang J, Shi K, Liu Z. · · 2022 · cited 57× · PMID 35935842 · DOI 10.3389/fphar.2022.950651