Metabolic Dysfunction-associated Steatohepatitis (MASH)
Conditions
Brief summary
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
GENETICVV-14303
will be administered via ultrasound guided intramuscular injections
Sponsors
Kriya Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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: 1. Within 6 months prior to Screening, or 2. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events, abnormal clinical laboratory values, abnormal physical exams, abnormal vital signs, abnormal ECGs, and abnormal imaging | 52 Weeks | Safety of VV-14303 in participants with MASH |
| Number of participants with improvement in overall metabolic health, as assessed by changes in serum biomarker levels | 6 weeks | Evaluate safety and efficacy of VV-14303 in participants with MASH in Part 1 |
| Changes in liver fat content as assessed by Magnetic Resonance Proton Density Fat Fraction (MRI-PDFF) as assessed by FibroScan® | 26 Weeks | Efficacy of VV-14303 in participants with MASH in Part 2 |
| Change in liver fat content as assessed by controlled attenuation parameter (CAP) as assessed by FibroScan® | 26 weeks | Efficacy of VV-14303 in participants with MASH in Part 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy associated with VV-14303 in participants with MASH | Week 26 and 52 | Liver stiffness as measured by change from Baseline transient elastography as assessed by FibroScan® |
| Part 1: Efficacy associated with VV-14303 in participants with MASH | 26 Weeks | Mean changes in liver fat content as assessed by MRI-PDFF as assessed by FibroScan® |
| Concentration of adeno-associated virus (AAV) vector-mediated transgene product in serum | 52 Weeks | Pharmacokinetics of VV-14303 transgene product |
Countries
New Zealand, United States
Contacts
CONTACTVP, Medical Affairs
Outcome results
None listed