Clinical Trial: VAL-1221 Delivered Intravenously in Ambulatory and Ventilator-free Patients With Late-Onset Pompe Disease

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Three-Month, Randomized, Parallel Active Control, Single and Repeat Dose, Dose-escalation Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of VAL-1221 D

Brief Summary: Phase I/II study enrolling up to 16 patients in a three-month, Randomized, Parallel Active Control, Single and Repeat Dose, Dose-escalation Study of the Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD) and Preliminary Efficacy of VAL-1221 Delivered Intravenously (IV) in Ambulatory and Ventilator-free Patients with Late-Onset GSD-II (Pompe Disease) Study

Detailed Summary:

Patients will be enrolled in a consecutive manner and randomized to either treatment with VAL-1221 or positive control (rhGAA) in cohorts of patients each: Cohort 1: VAL-1221 1 mg/kg IV (n=3) every other week or control (n=1) Cohort 2: VAL-1221 3 mg/kg IV (n=3) every other week or control (n=1) Cohort 3: VAL-1221 10 mg/kg IV (n=3) every other week or control (n=1)

Each patient randomized to VAL-1221 will receive 7 every other week IV infusions of VAL-1221 over 12 weeks. VAL-1221 cohorts will be enrolled in a sequential fashion. Patients randomized to rhGAA will be maintained on their current dose and regimen of Myozyme or Lumizyme.

The first patient in each cohort to receive VAL-1221 will be followed for any safety concerns (including infusion related reactions) for a minimum of 48 hours before the remaining VAL-1221-treated patients in the cohort receive infusions.

Once all patients in a cohort have been enrolled and the Data Safety Monitoring Board (DSMB) has reviewed at least one month of safety data in all patients, the next cohort may begin enrollment and treatment. A final assessment will occur approximately 2 weeks after the last dose of VAL-1221 to collect additional safety data. Safety will be assessed continuously throughout the study.

All patients who complete the study, including those maintained on rhGAA, will be offered inclusion in an extension study once the optimal dose of VAL-1221 has been determined.

Sponsor: Valerion Therapeutics, LLC

Current Primary Outcome:

• Incidences of treatment-emergent adverse events [ Time Frame: Baseline through 14 week follow-up ]
  Safety and tolerability of VAL-1221 will be determined by assessing treatment-emergent adverse events
• Immunogenicity outcome measure - incidences of anti-VAL-1221 antibodies [ Time Frame: Baseline through 14 week follow-up ]
  Changes from Baseline in antibody formation to VAL-1221
• Immunogenicity outcome measure - incidences of GAA antibodies [ Time Frame: Baseline through 14 week follow-up ]
  Changes from Baseline in GAA antibodies

Original Primary Outcome:

• Incidences of treatment-emergent adverse events [ Time Frame: Baseline through 24 month follow-up ]
  Safety and tolerability of VAL-1221 will be determined by assessing treatment-emergent adverse events
• Immunogenicity outcome measure - incidences of anti-VAL-1221 antibodies [ Time Frame: Baseline through 24 month follow-up ]
  Changes from Baseline in antibody formation to VAL-1221
• Immunogenicity outcome measure - incidences of GAA antibodies [ Time Frame: Baseline through 24 month follow-up ]
  Changes from Baseline in GAA antibodies

Current Secondary Outcome:

• Pharmacokinetics Outcome Measure of VAL-1221 given IV [ Time Frame: Day 1 through 14 week follow-up ]
  PK will be assessed by measuring serum levels of VAL-1221
• Pharmacodynamics Outcome Measure of VAL-1221 given IV [ Time Frame: Changes from Baseline to Weeks 12 ]
  Changes in urinary hex4 excretion, muscle glycogen and GAA activity
• Change from Baseline in the presence and activity of GAA on muscle biopsy [ Time Frame: Baseline to Week 12 ]
  GAA activity will be measure by biochemical methods to assess changes in GAA activity present in the muscle
• Change from Baseline in the amount of glycogen on muscle biopsy [ Time Frame: Baseline to Week 12 ]
  Glycogen content will be measured biochemically and histologically to determine the changes in glycogen present in the muscle

Original Secondary Outcome:

• Pharmacokinetics Outcome Measure of VAL-1221 given IV [ Time Frame: Baseline Weeks 2 and 24 ]
  PK will be assessed by measuring serum levels of VAL-1221
• Pharmacodynamics Outcome Measure of VAL-1221 given IV [ Time Frame: Changes from Baseline to Weeks 12 and 24 ]
  Changes in urinary hex4 excretion, muscle glycogen and GAA activity

Information By: Valerion Therapeutics, LLC

Dates:
Date Received: September 8, 2016
Date Started: March 2017
Date Completion: March 2018
Last Updated: March 15, 2017
Last Verified: March 2017