Pfizer B5161002

Principal Investigator: Russell Butterfield
Keywords: Anti-myostatin , DMD , DUCHENNE MUSCULAR DYSTROPHY , MUSCULAR DYSTROPHY , DUCHENNE , MYOSTATIN Department: Pediatric Administration
IRB Number: 00080422 Co Investigator: Nicholas Johnson
Specialty: Neurology
Sub Specialties: Muscular Dystrophy
Recruitment Status: Recruiting

Contact Information

Brianna Jensen

Brief Summary

1. Primary Safety and Efficacy

a. To determine the safety and tolerability of multiple ascending repeat IV doses of

PF-06252616 in ambulatory boys with DMD. Safety will be based on incidence of

abnormal and clinically relevant laboratory findings, physical examinations, weight,

vital signs, electrocardiogram (ECG), left ventricular ejection fraction (LVEF) by

cardiac magnetic resonance imaging (MRI) with gadolinium or echocardiogram (if

cardiac MRI is not available at the site), liver MRI, dual energy x-ray absorptiometry

(DXA) (bone mineral density), x-ray (bone age) and Columbia Suicide Severity

Rating Scale (C-SSRS) parameters by Week 49. Cardiac MRI with gadolinium is the

preferred method for cardiac imaging. If the subject has a contraindication to

gadolinium, cardiac MRI without gadolinium will be acceptable. Echocardiogram

may be substituted if it is not possible to perform cardiac MRI (if cardiac MRI is not

available at the site).

b. To demonstrate the efficacy of treatment with IV doses of PF-06252616 based on an
observed mean change from baseline on function (4 Stair Climb) as compared to
placebo following 49 weeks of treatment.

2. Secondary
a. To characterize the effects of PF-06252616 on muscle strength and other functional
assessments compared to placebo.

b. To evaluate the PD activity of PF-06252616 based on the percent change of muscle
volume from baseline as compared to placebo.

c. To evaluate the PD profile of PF-06252616 based on GDF-8 (myostatin) modulation
in blood.

d. To characterize the PK profile of PF-06252616.

e. To evaluate the immunogenicity of PF-06252616.

f. To characterize the long-term effects following approximately 2-years of treatment with PF-06252616 on functional assessments compared to historical control. 

g. To characterize the effects of PF-06252616 on muscle strength and functional assessments compared to placebo in subset of subjects who may demonstrate a rapid disease decline and with relatively low variability over a one-year period.

3. Exploratory
a. To evaluate biomarkers that may be informative in demonstrating the pharmacologic
effect of PF-06252616.

b. To evaluate biomarkers that may be informative for monitoring hepatic liver injury in
the setting of dystrophic muscle.

c. To evaluate the Functional Health Status.

d. To evaluate long term safety of PF-06252616 in subjects treated for >1 year.

e. To evaluate duration of treatment response following withdrawal and/or continuation
of treatment for >1 year.

f. To evaluate response in a delayed treatment group (Sequence Group 3, Period 2).

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the


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). Results must confirm the presence of a

mutation in the dystrophin gene(s) which is clinically consistent with the diagnosis of


2. Subjects who are able to perform the 4 stair climb in 0.33 but 1.6 stairs/second at


3. Evidence of a personally signed and dated informed consent and assent (where

appropriate) document indicating that the subject and a legally acceptable

representative/parent(s)/legal guardian have been informed of all pertinent aspects of

the study.

4. Subjects and their legal guardians who are willing and able to comply with scheduled

visits, treatment plan, laboratory tests, and other study procedures. Subjects will be

required to provide assent in compliance with local regulations and IRB requirements.

5. 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.

6. Adequate hepatic and renal function on screening laboratory assessments:

 GGT  upper limit of normal (ULN).

 Alkaline phosphatase  ULN.

 Total Bilirubin  ULN.

 Serum Albumin  LLN.

 Serum creatinine  ULN.

7. No underlying disposition for iron accumulation on screening laboratory assessments:

 Serum Iron 1.2 x ULN.

 Serum Ferritin 140 ng/mL.

 % Transferrin Saturation 50%.

8. No underlying disposition for bleeding disorder on screening laboratory assessments:

 PT/INR 1.25 x ULN.

 aPTT 1.25x ULN.

 Fecal occult blood is negative. If the fecal occult blood is positive due to known

pre-exiting medical condition (eg, any cause of rectal bleeding; hemorrhoids, anal

fissure) that is not considered to be clinically significant by the investigator, the

subject may be included.

9. Iron content estimate on the screening liver MRI is within the normal range as

determined by R2* value (R2*75 Hz at 1.5 T or R2*139 Hz at 3.0 T).

*Note: The 4 stair climb is expressed as a velocity in the inclusion criteria rather than a time

in seconds in an attempt to reduce the risk of subjects purposefully manipulating their

performance at screening in order to enroll. To determine eligibility subjects must have a

4 SC that is 2.5s but 12s on the screening assessment. It is not necessary to calculate the


Exclusion Criteria

Subjects with any of the following characteristics/conditions will not be included in the


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,  blockers, ARB (angiotensin II receptor 

blocker) or aldosterone blocker/thiazide diuretic; however they must have initiated

treatment more than 3 months prior to screening to ensure stable therapy.

6. Evidence or history of clinically significant hematological, renal, endocrine,

pulmonary, gastrointestinal, cardiovascular (including uncontrolled hypertension),

hepatic, neurologic, or allergic disease (including drug allergies, but excluding

untreated, asymptomatic, seasonal allergies at time of dosing).

7. Documented history of iron overload including hemochromatosis, beta thalassemia

major, beta thalassemia intermedia or hemolytic anemia.

8. Unwilling or unable (eg, metal implants, requires sedation) to undergo examination

with closed MRI without sedation.

9. Participation in other studies involving investigational drug(s) for a minimum of

30 days or within 5 half-lives (whichever is longer) prior to signing the informed

consent and/or during study participation.

10. Current or prior treatment with anti-myostatin, exon skipping, nonsense mutation

targeted therapies ever or more than 30 days of treatment with utrophin modifiers and

treatment with utrophin modifiers within 30 days prior to signing the informed

consent and/or during study participation.

11. Current or prior treatment within the past 3 months with androgens or human growth


12. Current treatment with immunosuppressant therapies (other than glucocorticoid

steroids), aminoglycosides (eg, gentamicin), multi-vitamins with iron and iron

supplements and other investigational therapies (including idebenone).

13. History of allergic or anaphylactic reaction to a therapeutic or diagnostic protein or

additives of this investigational product (histidine, sucrose, edetic acid

[ethylenediaminetetraacetic acid], and polysorbate 80).

14. Have suicidal ideation and behavior associated with actual intent and/or method

and/or plan and/or action (eg, self-harming behaviors) in the past 6 months based on

the Columbia-Suicide Severity Rating Scale (C-SSRS Children’s Baseline/Screening

Appendix 1) or at baseline (C-SSRS Children’s Since Last Visit Appendix 2).

15. Subjects who, in the opinion of the investigator, are biologically capable of having

children and are sexually active who are unwilling or unable to use a condom to

prevent potential transfer of exposure to drug through semen; male subjects of

childbearing potential, with their female partners at risk for pregnancy, who are

unwilling or unable to use a highly effective method of contraception as outlined in

this protocol (in addition to the condom to prevent potential transfer of drug through

semen) for the duration of the study and through completion on final study visit. 

16. 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.

17. Other severe acute or chronic medical or psychiatric condition or laboratory

abnormality that may increase the risk associated with study participation or

investigational product administration or may interfere with the interpretation of

study results and, in the judgment of the investigator, would make the subject

inappropriate for entry into this study.

Note: Screening results considered by the investigator to be transient and inconsistent with

the subject’s clinical condition may be repeated once during the screening period for

confirmation of eligibility. The reason for repeating the assessment should be documented.