A Three-Month, Open-Label, Randomized, Dose-escalation Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of VAL-1221 Versus Myozyme®/Lumizyme® in Patients With Late-Onset GSD-II (Pompe Disease) Followed by Open-Label Treatment With VAL-1221 in All Patients

Status: Terminated

Location: See all (3) locations...

Intervention Type: Drug

Study Type: Interventional

Study Phase: Phase 1/Phase 2

SUMMARY

This Phase I/II open-label, randomized, dose-escalation study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of VAL-1221 versus Myozyme®/Lumizyme® in participants with late-onset glycogen storage disease-II (GSD-II) (Pompe disease)

Eligibility

Participation Requirements

Sex: All

Minimum Age: 18

Healthy Volunteers: No

View:

• Participant is able and willing to provide informed consent prior to any study procedures are performed

• Diagnosis of GSDII based on one of the following:

• Endogenous cultured skin fibroblast GAA activity less than (<) 40 percent (%) of adult normal level

• Endogenous whole blood or dried blood spot GAA activity in deficiency range

• Genetic analysis showing pathogenic variants in both alleles

• Onset of Pompe disease-related symptoms after 1 year of age

• Previously treated with Myozyme or Lumizyme for at least 12 months and on a stable regimen for the past 6 months

• Sexually active participants who are willing to use an acceptable method of contraception (abstinence, oral contraceptives, barrier method with spermicide, surgical sterilization, implanted or injectable contraceptives with a stable dose for at least 1 month prior to Baseline, hormonal intra-uterine device [IUD] inserted at least 1 month prior to Baseline) during the study and for 30 days after completion of treatment

• If participant is female and not considered to be of childbearing potential, she is at least 2 years post-menopause, has undergone a tubal ligation, a total hysterectomy or bilateral oophorectomy

• If participant is female and of childbearing potential, she has a negative serum pregnancy test during screening and Baseline and must be willing to undergo pregnancy testing at specific intervals during the study

• Participant meets at least one of the following criteria: greater than (>) 30% and <80% predicted upright forced volume capacity (FVC) or participant is able to walk >20% but <80% predicted normal on 6-minute walk test with or without use of assistive devices

• Able to comply with protocol requirements

Locations

United States

California

University of California, Irvine

Orange

North Carolina

Duke University Medical Center

Durham

Other Locations

United Kingdom

National Hospital for Neurology and Neurosurgery

London

Time Frame

Start Date: June 21, 2017

Completion Date: March 25, 2020

Participants

Target number of participants: 12

Treatments

Experimental: VAL-1221 3 mg/kg

Part 1: Participants will receive VAL-1221 3 mg/kg IV infusion every other week for 12 weeks, inclusive, for a total of 7 infusions.~Part 2: Participants from Part 1 of the study who were randomized to VAL-1221 3 mg/kg can enter Part 2 of the study and receive VAL-1221 at a dose of 3 mg/kg IV infusion every other week. The dose can be increased by the Investigator to 10 mg/kg and further to 30 mg/kg (after at least 12 weeks of dosing at 10 mg/kg), depending upon the pharmacodynamics, efficacy, and safety data.

Experimental: VAL-1221 10 mg/kg

Part 1: Participants will receive VAL-1221 10 mg/kg IV infusion every other week for 12 weeks, inclusive, for a total of 7 infusions.~Part 2: Participants from Part 1 of the study who were randomized to VAL-1221 10 mg/kg can enter Part 2 of the study and receive VAL-1221 at a dose of 10 mg/kg IV infusion every other week. The dose can be increased by the Investigator to 30 mg/kg IV infusion, depending upon the pharmacodynamics, efficacy, and safety data.

Experimental: VAL-1221 30 mg/kg

Part 1: Participants will receive VAL-1221 30 mg/kg IV every other week for 12 weeks, inclusive, for a total of 7 infusions.~Part 2: Participants from Part 1 of the study who were randomized to VAL-1221 30 mg/kg can enter Part 2 of the study and receive VAL-1221 at a dose of 30 mg/kg IV inufsion every other week.

Active Comparator: rhGAA

Part 1: Participants will be maintained on their current dose and regimen of Myozyme or Lumizyme.~Part 2: Participants from Part 1 of the study who were randomized to rhGAA can enter Part 2 of the study and receive VAL-1221 either 3 mg/kg, 10 mg/kg, or 30 mg/kg (based on the dose of VAL-1221 in respective cohorts to which they were randomized in Part 1) IV infusion every other week.

Authors

Priya Kishnani, Tahseen Mozaffar, Robin Lachmann

Related Therapeutic Areas

Pompe Disease

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