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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02898753
• Date of registration: 08/09/2016
• Prospective Registration: Yes
• Primary sponsor: Valerion Therapeutics, LLC
• Public title: VAL-1221 Delivered Intravenously in Ambulatory and Ventilator-free Participants With Late-Onset Pompe Disease
• Scientific 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
• Date of first enrolment: June 21, 2017
• Target sample size: 12
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02898753
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United Kingdom, United States

Contacts

• Name: Hal Landy, MD
• Affiliation: Valerion Therapeutics, LLC

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pompe Disease

Intervention(s)

Drug: RhGAA

Drug: VAL-1221

Primary Outcome(s)

Number of Participants With Infusion-Associated Reactions to VAL-1221 [Time Frame: Baseline of Study Part 1 though Month 24 of Study Part 2]

Number of Treatment-related Treatment-emergent Adverse Events (TEAEs) [Time Frame: Baseline of Study Part 1 though Month 24 of Study Part 2]

Percentage of Participants with Anti-VAL-1221 Antibodies [Time Frame: Baseline of Study Part 1 though Month 24 of Study Part 2]

Percentage of Participants with GAA Antibodies [Time Frame: Baseline of Study Part 1 though Month 24 of Study Part 2]

Secondary Outcome(s)

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 12, 24, and 36 of Study Part 2]

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 12, 24, 36]

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 12, 24, 36]

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 12, 24, 36]

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 12, 24, 36]

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]

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 12, 24, 36]

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 12, 24, and 36 of Study Part 2]

Change from Baseline in Creatinine Excretion at Months 6, 9, and 12 [Time Frame: Baseline of Study Part 1, Months 12, 24, 36 of Study Part 2]

Change from Baseline in the Muscle Glycogen Content at Week 12 [Time Frame: Baseline of Study Part 1, Week 12 Study Part 1]

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 12, 24, 36]

Secondary ID(s)

VAL1221-201-16

Source(s) of Monetary Support

Please refer to primary and secondary sponsors