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

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ClinicalTrials.gov Identifier: NCT02898753
Recruitment Status : Active, not recruiting
First Posted : September 13, 2016
Last Update Posted : October 12, 2018
Sponsor:
Information provided by (Responsible Party):
Valerion Therapeutics, LLC

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)

Condition or disease Intervention/treatment Phase
Pompe Disease Drug: VAL-1221 Drug: RhGAA Phase 1 Phase 2

Detailed Description:
The study will be conducted in two parts. Part 1 is a 3-month active control phase which comprises 3 sequential cohorts of 4 participants each randomized to treatment with either VAL-1221 (at 3, 10, or 30 milligrams/kilogram [mg/kg]) or positive control (recombinant human acid alpha-glucosidase [rhGAA]). Eligible participants who complete Part 1, including those maintained on rhGAA, will be offered inclusion in Part 2 of the study. Part 2 is a 9-month uncontrolled extension to evaluate long-term effects of VAL-1221 given by intravenous (IV) infusion once every other week at doses up to 30 mg/kg.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 21, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
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.

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

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.

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

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.

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

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.

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

Drug: RhGAA
Active comparator
Other Names:
  • Myozyme
  • Lumizyme




Primary Outcome Measures :
  1. Number of Treatment-related Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline of Study Part 1 though Month 24 of Study Part 2 ]
  2. Number of Participants With Infusion-Associated Reactions to VAL-1221 [ Time Frame: Baseline of Study Part 1 though Month 24 of Study Part 2 ]
  3. Percentage of Participants with Anti-VAL-1221 Antibodies [ Time Frame: Baseline of Study Part 1 though Month 24 of Study Part 2 ]
  4. Percentage of Participants with GAA Antibodies [ Time Frame: Baseline of Study Part 1 though Month 24 of Study Part 2 ]

Secondary Outcome Measures :
  1. Pharmacokinetics of VAL-1221 in Plasma: Maximum Observed Concentration (Cmax) [ Time Frame: Part 1: Pre-infusion, end of infusion (EOI) (infusion duration 1 mg/kg/hour), at 0.25, 0.5, 1, 2, 4, 12, 24, 48 and 336 hours after EOI on Days 1, 2, 3 and Week 12; Part 2: Pre-infusion on Weeks 12, 14, 16, 18, 20, 22, Months 6, 9, 12 ]
  2. Pharmacokinetics of VAL-1221 in Plasma: Time to Reach Maximum Concentration (Tmax) [ Time Frame: Part 1: Pre-infusion, end of infusion (EOI) (infusion duration 1 mg/kg/hour), at 0.25, 0.5, 1, 2, 4, 12, 24, 48 and 336 hours after EOI on Days 1, 2, 3 and Week 12; Part 2: Pre-infusion on Weeks 12, 14, 16, 18, 20, 22, Months 6, 9, 12 ]
  3. Pharmacokinetics of VAL-1221 in Plasma: Area Under the Concentration Time Curve (AUC) [ Time Frame: Part 1: Pre-infusion, end of infusion (EOI) (infusion duration 1 mg/kg/hour), at 0.25, 0.5, 1, 2, 4, 12, 24, 48 and 336 hours after EOI on Days 1, 2, 3 and Week 12; Part 2: Pre-infusion on Weeks 12, 14, 16, 18, 20, 22, Months 6, 9, 12 ]
  4. Pharmacokinetics of VAL-1221 in Plasma: Terminal Elimination Half-Life ( t1/2) [ Time Frame: Part 1: Pre-infusion, end of infusion (EOI) (infusion duration 1 mg/kg/hour), at 0.25, 0.5, 1, 2, 4, 12, 24, 48 and 336 hours after EOI on Days 1, 2, 3 and Week 12; Part 2: Pre-infusion on Weeks 12, 14, 16, 18, 20, 22, Months 6, 9, 12 ]
  5. Pharmacokinetics of VAL-1221 in Plasma: Apparent Total Body Clearance (CL) [ Time Frame: Part 1: Pre-infusion, end of infusion (EOI) (infusion duration 1 mg/kg/hour), at 0.25, 0.5, 1, 2, 4, 12, 24, 48 and 336 hours after EOI on Days 1, 2, 3 and Week 12; Part 2: Pre-infusion on Weeks 12, 14, 16, 18, 20, 22, Months 6, 9, 12 ]
  6. Pharmacokinetics of VAL-1221 in Plasma: Apparent Volume (V) [ Time Frame: Part 1: Pre-infusion, end of infusion (EOI) (infusion duration 1 mg/kg/hour), at 0.25, 0.5, 1, 2, 4, 12, 24, 48 and 336 hours after EOI on Days 1, 2, 3 and Week 12; Part 2: Pre-infusion on Weeks 12, 14, 16, 18, 20, 22, Months 6, 9, 12 ]
  7. Change from Baseline in Urinary Hexose Tetrasaccharide (hex4) Excretion at Week 12, Months 6, 9, and 12 [ Time Frame: Baseline of Study Part 1, Week 12 of Study Part 1, Months 6, 9, and 12 of Study Part 2 ]
  8. Change from Baseline in Serum Creatine Kinase (CK) at Week 12, Months 6, 9, and 12 [ Time Frame: Baseline of Study Part 1, Week 12 of Study Part 1, Months 6, 9, and 12 of Study Part 2 ]
  9. Change from Baseline in the Amount of Acid Alpha Glucosidase (GAA) Activity Present in Muscle at Week 12 [ Time Frame: Baseline of Study Part 1, Week 12 of Study Part 1 ]
  10. Change from Baseline in the Muscle Glycogen Content at Week 12 [ Time Frame: Baseline of Study Part 1, Week 12 Study Part 1 ]
  11. Change from Baseline in Creatinine Excretion at Months 6, 9, and 12 [ Time Frame: Baseline of Study Part 1, Months 6, 9, and 12 of Study Part 2 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02898753


Locations
United States, California
University of California, Irvine
Orange, California, United States, 92868
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United Kingdom
National Hospital for Neurology and Neurosurgery
London, United Kingdom, WC1N 3BG
Sponsors and Collaborators
Valerion Therapeutics, LLC
Investigators
Study Director: Hal Landy, MD Valerion Therapeutics, LLC

Responsible Party: Valerion Therapeutics, LLC
ClinicalTrials.gov Identifier: NCT02898753     History of Changes
Other Study ID Numbers: VAL1221-201-16
First Posted: September 13, 2016    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Valerion Therapeutics, LLC:
GSD-II
Pompe Disease
Glycogen Storage Diseases
GAA

Additional relevant MeSH terms:
Glycogen Storage Disease Type II
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Glycogen Storage Disease
Carbohydrate Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases