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| ID | Type | Description | Link |
|---|---|---|---|
| Harmony-HHT | Other Identifier | Atavistik Bio Inc |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: 60 mg QD | Experimental | Active drug, once daily |
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| Part 1: 100 mg QD | Experimental | Active drug, once daily |
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| Part 1: 60 BID | Experimental | Active drug, twice daily |
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| Part 1: Placebo | Experimental | Control Arm |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ATV-1601 | Drug | Administered orally, daily |
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| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Safety and tolerability | Number and severity of treatment-emergent adverse events (TEAEs) and study drug-related TEAEs | 16 weeks |
| Part 2: Safety and tolerability | Type, incidence, severity, timing, seriousness and relatedness of AEs and laboratory abnormalities | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Change in Epistaxis duration | 28-day total duration compared to baseline | 16 weeks |
| Part 1: Epistaxis frequency | 28-day frequency of nosebleeds compared to baseline |
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Inclusion Criteria:
Exclusion Criteria:
Additional Criteria for Open-Label Extension:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Contact | 857-285-5400 | Studydirector@atavistikbio.com |
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| ID | Term |
|---|---|
| D013683 | Telangiectasia, Hereditary Hemorrhagic |
| D001165 | Arteriovenous Malformations |
| D014652 | Vascular Diseases |
| D020141 | Hemostatic Disorders |
| D006402 | Hematologic Diseases |
| D004194 | Disease |
| D013684 | Telangiectasis |
| D006474 | Hemorrhagic Disorders |
| D002318 | Cardiovascular Diseases |
| D054079 | Vascular Malformations |
| ID | Term |
|---|---|
| D006425 | Hemic and Lymphatic Diseases |
| D018376 | Cardiovascular Abnormalities |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| D002214 | Capsules |
| ID | Term |
|---|---|
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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Participants will be randomized to one of 3 doses of ATV-1601 or placebo
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| Placebo | Drug | Administered orally, daily |
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| 16 weeks |
| Part 1: Epistaxis intensity | 28-day average epistaxis intensity (6-point scale) of nosebleeds compared to baseline | 16 weeks |
| Part 1: Intensity-weighted epistaxis duration | 28-day intensity-weighted duration of nosebleeds | 16 weeks |
| Part 1: Epistaxis Severity Score (ESS) | The Epistaxis Severity Score (ESS) is a validated 6-question instrument with scores ranging from 0 to 10, where higher scores indicate more severe epistaxis symptoms. | 16 weeks |
| Part 1: Change in Hemoglobin | Hemoglobin levels compared to baseline | 16 weeks |
| Part 1: Change in Parenteral iron use | Amount of parenteral iron administered compared to 16-weeks prior to treatment initiation | 16 weeks |
| Part 1: Change in Blood transfusion requirements | Amount of packed red blood cell (PRBC) transfusions and rate of transfusion independence compared to 16-weeks prior to treatment initiation | 16 Weeks |
| Part 1: Pharmacokinetics - Maximum observed concentration (Cmax) | Maximum plasma concentration | 16 Weeks |
| Part 1: Pharmacokinetics - Area under the concentration-time curve over the dosing interval (AUCtau) | Systemic exposure of ATV-1601 over the dosing interval | 16 Weeks |
| Part 1: Pharmacokinetics - Area under the concentration-time curve extrapolated to infinity (AUCinf) | Total systemic exposure of ATV-1601 extrapolated to infinite time | 16 Weeks |
| Part 1: Pharmacokinetics - Time to maximum concentration (Tmax) | Time to reach maximum plasma concentration | 16 Weeks |
| Part 1: Pharmacokinetics - minimum concentration (Cmin) | Pre-dose trough plasma concentration | 16 Weeks |
| Part 1: Pharmacokinetics - Half-life (t½) | Time required for plasma concentration to decrease by half | 16 Weeks |
| Part 2: Epistaxis duration | 28-day total duration every 4 weeks | Up to 2 years |
| Part 2: Epistaxis frequency | Total number of nosebleeds every 4 weeks | Up to 2 years |
| Part 2: Epistaxis Severity Score (ESS) | Severity of nosebleeds using a score of 0-10 automatically calculated based on responses to 6 questions. | At 12 weeks and every 12 weeks thereafter up to study completion |
| Part 2: Change in Hemoglobin | Hemoglobin levels compared to baseline | Monthly during Part 2 |
| Part 2: Parenteral iron use | Total amount of parenteral iron infused (mg) compared to baseline (12 weeks prior to treatment initiation | At 12 weeks and every 12 weeks thereafter up to study completion |
| Part 2: Blood transfusion requirements | Total number of packed red blood cell (PRBC) transfusions (units) compared to baseline | At 12 weeks and every 12 weeks thereafter during part 2 |
| Part 2: Transfusion independence | Proportion of participants who do not require PRBC transfusions | At 12 weeks and every 12 weeks thereafter during part 2 |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |