Overview
This is a 2-part study evaluating ATV-1601 in participants with moderate to severe HHT. Part 1 is a randomized, double-blind, placebo-controlled study evaluating 3 dosing regimens of ATV-1601. Patients completing Part 1 may participate in the Part 2 open-label extension to receive ATV-1601.
Description
Part 1: This is a Phase 1/2 proof-of-concept, double-blind, multicenter, placebo-controlled study to evaluate the safety, pharmacokinetics and efficacy of 3 oral dosing regimens of ATV-1601. Participants who meet eligibility requirements will be randomized in a double-blind manner to one of 3 doses of ATV-1601 or placebo. Participants will receive double-blind study treatment for a 16-week period.
Part 2: Eligible participants who complete Part 1 may enroll in an open-label extension study to receive up to 2 years of additional treatment. All participants in the open-label extension will receive ATV-1601. Once the recommended Phase 2 dose (RP2D) is determined based on Part 1, all participants in Part 2 will have the option to switch to the RP2D.
Eligibility
Inclusion Criteria:
- Ability to provide informed consent prior to any study-specific procedures
- Confirmed diagnosis of hereditary hemorrhagic telangiectasia (HHT) based on Curaçao criteria
- Moderate to severe HHT with an ESS ≥ 4
- Anemia at Screening and/or requirement for at least 1 red-cell unit (RUE) in the previous 6 months
- Adequate hematologic, renal, and hepatic function per protocol-defined laboratory criteria
- Use highly effective contraception during the study and for a protocol-defined period after last dose
Exclusion Criteria:
- Clinically significant abnormalities of glucose metabolism including diagnosed Type 1 or uncontrolled Type 2 diabetes
- Chronic cardiac disease, or cardiac rhythm abnormalities
- History of significant cardiovascular, hepatic, renal, or hematologic disease not related to HHT that may confound study results
- Use of prohibited concomitant medications within a protocol-defined washout period prior to first dose (including strong CYP modulators and certain herbal supplements)
- Recent (within 6 weeks) major surgery or local ablative procedures, or procedures on nasal telangiectasias
- Prior AKT inhibitor
- Pregnant or breastfeeding women
Additional Criteria for Open-Label Extension:
- Participants must complete the double-blind treatment period (Part 1)
