Harmony-HHT: ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)

A Randomized, Placebo-Controlled, Double-Blind, Proof-of-Concept Study of ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)

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.

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.

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)