A Study of VV-14303 for the Treatment of Metabolic Dysfunction-associated Steatohepatitis (MASH)

Official title

A Phase 1/2, First-in-Human, Multi-Arm, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Efficacy of VV-14303, an Adeno-associated Virus Vector-mediated Fibroblast Growth Factor 21 (FGF21) Gene Therapy, in Adults With Metabolic Dysfunction-associated Steatohepatitis (MASH)

Overview

A Study of VV-14303 for the Treatment of Metabolic dysfunction-associated steatohepatitis (MASH)

Detailed description

A Phase 1/2, First-in-Human, Multi-Arm, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of VV-14303, an Adeno-associated Virus Vector-mediated Fibroblast Growth Factor 21 (FGF21) Gene Therapy, in Adults with Metabolic dysfunction associated steatohepatitis (MASH) (the RESTORE Study)

Interventions

• Genetic VV-14303
  will be administered via ultrasound guided intramuscular injections

Primary outcome measures

• Incidence and severity of adverse events, abnormal clinical laboratory values, abnormal physical exams, abnormal vital signs, abnormal ECGs, and abnormal imaging [Time frame: 52 Weeks]
• Number of participants with improvement in overall metabolic health, as assessed by changes in serum biomarker levels [Time frame: 6 weeks]
• Changes in liver fat content as assessed by Magnetic Resonance Proton Density Fat Fraction (MRI-PDFF) as assessed by FibroScan® [Time frame: 26 Weeks]
• Change in liver fat content as assessed by controlled attenuation parameter (CAP) as assessed by FibroScan® [Time frame: 26 weeks]

Secondary outcome measures (7)

• Efficacy associated with VV-14303 in participants with MASH [Time frame: Week 26 and 52]
• Efficacy associated with VV-14303 in participants with MASH [Time frame: Week 26 and 52]
• Efficacy associated with VV-14303 in participants with MASH [Time frame: 52 Weeks]
• Efficacy associated with VV-14303 in participants with MASH [Time frame: 52 Weeks]
• Part 1: Efficacy associated with VV-14303 in participants with MASH [Time frame: 26 Weeks]
• Part 1: Efficacy associated with VV-14303 in participants with MASH [Time frame: 26 Weeks]
• Concentration of adeno-associated virus (AAV) vector-mediated transgene product in serum [Time frame: 52 Weeks]

Eligibility criteria

Inclusion criteria

• Participant is capable of providing signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol
• Must be 18 to 75 years of age (inclusive) at Screening
• Body Mass Index (BMI) of 25 to <40 kg/m2 (inclusive)
• Male participants must agree to use a highly effective contraception during the Treatment Period and at least 12 months after administration of VV-14303. Female participants must not be a woman of child-bearing potential (WOCBP)
• Biopsy-confirmed MASH
• Previous history or presence of ≥2 of the following metabolic risk factors: obesity (BMI ≥25 kg/m²), hypertension (blood pressure \[BP\] ≥140/90 mmHg or on antihypertensive medication), dyslipidemia (triglycerides ≥150 mg/dL or high-density lipoprotein cholesterol \[HDL-C\] <40 mg/dL in men/<50 mg/dL in women or on lipid-lowering therapy), type 2 diabetes mellitus
• Must be willing to refrain from the donation of blood, plasma, platelets, eggs, or sperm during the 12-month post-treatment follow-up period

Exclusion criteria

• Presence of alternate and/or additional liver disease etiologies at Screening, including but not limited to chronic viral hepatitis, autoimmune hepatitis
• Use of treatments for metabolic syndrome management, including oral antidiabetic drugs (OADs) (e.g., metformin), incretin mimetics (GLP-1 receptor agonists or GLP-1/gastric inhibitory polypeptide \[GIP\] agonists) or other glucose-lowering agents that has not been stable for at least 6 months prior to Screening
• Use of Resmetirom that has not been stable for at least 6 months prior to Screening visit
• Any medical, cognitive, or psychiatric condition that, in the opinion of the Investigator, could contraindicate the use of the investigational drug, make consistent study assessment and follow-up over the 12-month Post-Treatment Follow-up Period unlikely, or would make the participant an unsafe study candidate.
• Type 1 diabetes, or poorly controlled type 2 diabetes (HbA1c > 8.0% at Screening)
• History of major trauma to the muscle(s) intended for IM injection meeting any of the following criteria:

• Within 6 months prior to Screening, or
• At any timepoint prior to Screening with continued neurologic or musculoskeletal symptoms
• Prior participation in any systemic experimental treatment or receiving any other systemic investigational treatment including within 6 weeks or 5 half-lives of the active ingredient (whichever is longer) prior to the start of Screening
• Any vaccination or planned vaccination 30 days prior to dosing, or planned vaccination 8 weeks post dosing
• Previously received AAV or adenoviral therapy or participation in any previous gene therapy trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• Kriya Clinical Trial Site — Chandler
• Kriya Clinical Trial Site — Lady Lake

New Zealand · 1 center

• Kriya Clinical Trial Site — Auckland

Identifiers

NCT: NCT07732400 · KRIYA-497-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗