VAL-1221 Delivered Intravenously in Ambulatory and Ventilator-free Participants With Late-Onset Pompe Disease

NCT ID: NCT02898753

Last Updated: 2020-06-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-21
• Study Completion Date: 2020-03-25

Brief 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)

Detailed Description

Part 1 comprises 3 sequential cohorts of 4 patients each randomized to treatment with either VAL-1221 (at 3, 10, or 30 mg/kg) or positive control (rhGAA). Patients randomized to VAL-1221 will receive 7 intravenous (IV) infusions of VAL-1221 (one infusion every other week) over 12 weeks. Control patients will continue receiving their accustomed dose and regimen of Myozyme®. Part 2 is an uncontrolled extension to evaluate long-term effects of VAL-1221 given by IV infusion once every other week at doses up to 40 mg/kg.

Conditions

Pompe Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

VAL-1221

Intervention Type: DRUG

VAL-1221 3, 10, or 30 mg/kg as per the dose and schedule specified in the arm group description

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.

Group Type: EXPERIMENTAL

VAL-1221

Intervention Type: DRUG

VAL-1221 3, 10, or 30 mg/kg as per the dose and schedule specified in the arm group description

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.

Group Type: EXPERIMENTAL

VAL-1221

Intervention Type: DRUG

VAL-1221 3, 10, or 30 mg/kg as per the dose and schedule specified in the arm group description

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.

Group Type: ACTIVE_COMPARATOR

VAL-1221

Intervention Type: DRUG

VAL-1221 3, 10, or 30 mg/kg as per the dose and schedule specified in the arm group description

RhGAA

Intervention Type: DRUG

Active comparator

Interventions

VAL-1221

VAL-1221 3, 10, or 30 mg/kg as per the dose and schedule specified in the arm group description

Intervention Type: DRUG

RhGAA

Active comparator

Intervention Type: DRUG

Other Intervention Names

Myozyme; Lumizyme

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• Cardiac involvement in first year of life
• Anti-GAA antibody titers >1:51,200 at two time points
• Prior use of chaperone therapy for GSD-II within the last 12 months
• Use of immunosuppressive medication other than glucocorticoids within 6 months prior to study enrollment
• Use of invasive ventilatory assistance other than Bilevel Positive Airway Pressure (BiPAP) at night or during periods of rest
• Has received any investigational medication or has enrolled in any study involving investigational drugs or therapies within 30 days prior to first dose of study drug
• Start of or change in usual regimen of albuterol or respiratory muscle training within 30 days prior to first dose of study drug
• History of sensitivity to any of the constituents of the study drug
• Participant is breastfeeding or planning to become pregnant or to breastfeed during the study or is currently breastfeeding
• Participant has a medical condition or circumstance that, in the opinion of the investigator, might compromise the participant's ability to comply with the protocol or the participant's well-being or safety
• Participant has any condition that, in the view of the investigator, places the participant at high risk of poor treatment compliance or of not completing the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Valerion Therapeutics, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hal Landy, MD

Role: STUDY_DIRECTOR

Valerion Therapeutics, LLC

Locations

University of California, Irvine

Orange, California, United States

Duke University Medical Center

Durham, North Carolina, United States

National Hospital for Neurology and Neurosurgery

London, , United Kingdom

Countries

United States; United Kingdom

Other Identifiers

VAL1221-201-16

Identifier Type: -

Identifier Source: org_study_id