A Trial of PF-06252616 in Ambulatory Participants With LGMD2I

NCT02841267 | Completed Phase 1 Results

• 1 other identifier: WI203720
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The investigational product PF 06252616, a humanized anti myostatin monoclonal antibody that neutralizes myostatin (GDF8) is in development for the treatment of Limb Girdle Muscular Dystrophy 2I (LGMD2I) to preserve and/or improve muscle function. This study will provide the clinical assessment of the safety, tolerability, Pharmacokinetics and Pharmacodynamics of PF 06252616 following repeat IV doses in ambulatory adults with LGMD2I.

Conditions

LGMD2I

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose Limiting or Intolerability Treatment Related Adverse Events

  Adverse events include subject-reported symptoms as well as clinically-significant changes in laboratory testing, vital signs, and suicide screening (based on the Columbia Suicide Severity Rating Scale).

  Baseline through 64 weeks

Secondary Outcomes (10)

• Maximum Observed Serum Concentration at Steady State (Cmax, ss) of GDF-8

  Day 337 and Day 393 for Cohort 1; Day 113 and 169 for Cohorts 2 and 3

• Minimum Observed Serum Trough Concentration at Steady State (Ctrough,ss) of GDF-8

  Day 337 and Day 393 for Cohort 1; Day 113 and 169 for Cohorts 2 and 3

• Maximum Observed Serum Concentration (Cmax) of PF-06252616

  Day 113 and Day 169

• Minimum Observed Serum Trough Concentration (Ctrough) of PF-06252616

  Day 113 and Day 169

• Immunogenicity: Incidence of Anti-drug Antibody

  Baseline through 96 weeks

Study Arms (3)

Low Dose, Cohort 1

ACTIVE COMPARATOR

4 subjects will be enrolled in cohort 1 and will receive an initial dose of 5mg/kg PF 06252616 IV every 4 weeks. Following 32 weeks of treatment and a safety review, if no stopping rules have been met, subjects will be receive an additional 32 weeks of treatment with 40 mg/kg PF 06252616 IV every 4 weeks.

Drug: PF 06252616

Middle dose, Cohort 2

ACTIVE COMPARATOR

8 subjects will be enrolled in cohort 2 and receive 20 mg/kg of PF 06252616 IV every 4 weeks for 32 weeks.

Drug: PF 06252616

High dose, Cohort 3

ACTIVE COMPARATOR

8 subjects will be enrolled in cohort 3 and receive 40 mg/kg of PF06252616 IV every 4 weeks for 32 weeks.

Drug: PF 06252616

Interventions

PF 06252616 DRUG

High dose, Cohort 3; Low Dose, Cohort 1; Middle dose, Cohort 2

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients age ≥ 18
• Diagnosis of LGMD2I as defined by clinical presentation consistent with LGMD2I and FKRP gene testing showing biallelic alterations known or likely to be pathogenic. 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).
• Ability to walk/run 10m
• Ability to rise from chair
• Adequate hepatic and renal function on screening laboratory assessments
• Iron content estimate on the screening liver MRI within the normal range as determined by R2\* value (R2\* ≤ 139 Hz at 3.0T).
• Participant must provide written informed consent for participating in study.
• Participant must possess the ability, per the Principal Investigator (PI), to understand and comply with protocol instruction for the entire duration of the study.

You may not qualify if:

• Known cognitive impairment or behavioral issues that would impede the ability to provide informed consent or to follow study 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 consent. Prior lower limb fractures must be fully healed and at least 3 months from injury dates.
• Previous treatment with another investigational product within 30 days or 5 half-lives, (whichever is longer) prior to consenting.
• Corticosteroid treatment within 3 months prior to consenting.
• Compromised cardiac function (left ventricular ejection fraction \<50%).
• Unwilling or unable (e.g. metal implants, requires sedation) to undergo examination with closed MRI without sedation.
• History of allergic or anaphylactic reaction to a therapeutic or diagnostic protein.
• Female subjects who are pregnant or nursing.
• Subjects who, are biologically capable of having children who are unwilling or unable to use highly effective methods of contraception (as outlined in this protocol) during sexual activity for the duration of the study and through completion of final study visit.
• Predisposition to iron accumulation. (Serum iron \>1.2 X ULN, serum ferritin \>1.2 ULNN).
• Underlying disposition for bleeding disorder on screening laboratory assessment (PT/INR\>1.25 X ULN, aPTT \> 1.25 ULN, fecal occult blood is positive)
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, neurologic, or allergic disease.
• Unwillingness or inability to comply with the requirements of this protocol (in the opinion of the PI) including, but not limited to, the presence of any condition (physical, mental, or social) that is likely to affect the participant's ability to return for study visits or adhere to the visit schedule.

Sponsors & Collaborators

• Kathryn Wagner: lead
• Pfizer: collaborator

Study Sites (1)

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• Leung DG, Bocchieri AE, Ahlawat S, Jacobs MA, Parekh VS, Braverman V, Summerton K, Mansour J, Bibat G, Morris C, Marraffino S, Wagner KR. Longitudinal functional and imaging outcome measures in FKRP limb-girdle muscular dystrophy. BMC Neurol. 2020 May 19;20(1):196. doi: 10.1186/s12883-020-01774-5.

  PMID: 32429923 DERIVED

MeSH Terms

Conditions

Muscular Dystrophy, Limb-Girdle, Type 2I

Results Point of Contact

• Title: Dr. Kathryn R. Wagner
• Organization: Hugo W. Moser Research Institute at Kennedy Krieger Inc.

wagnerk@kennedykrieger.org

443-923-9525

Study Officials

• Kathryn R Wagner, MD/PhD

  Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Center for Genetic Muscle Disorders

Study Record Dates

• First Submitted: July 12, 2016
• First Posted: July 22, 2016
• Study Start: July 1, 2016
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: October 19, 2020
• Results First Posted: October 19, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)