NCT05261711

AB1 in Adult Patients with Sickle Cell Disease (SCD)

A Phase 1/2, Open-Label, Dose Escalating Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AB1 in Adult Patients with Sickle Cell Disease (SCD)

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: Nirmish Shah · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Not accepted

Summary

This will be an open-label, dose escalating study with a starting dose of 2mg. Up to 6 additional cohorts will be enrolled at subsequently higher doses of 4mg, 8mg, 10mg, 12mg, 16mg, and 32mg. In each dose escalation cohort, each dose will be taken orally, once daily, for 8 weeks.

Detailed description

This will be an open-label, dose escalating study with a starting dose of 2mg. Up to 4 additional cohorts will be enrolled at subsequently higher doses of 4mg, 8mg, 16mg, and 32mg. * Cohort 1 - Two (2) patients will be enrolled at the 2mg dose level for 8 weeks of treatment. After both patients have received at least 4 weeks of treatment, if there are no adverse events ≥Grade 2 that are related (possibly, probably, or definitely) to the study drug, then the study will proceed to the next dose level. Note that if ≥Grade 2 toxicity is seen at this dose level, the study drug regimen may be modified (eg, twice or thrice weekly versus daily dosing). * Cohort 2 - Two (2) patients will be enrolled at the 4mg dose level for 8 weeks of treatment. After both patients have received at least 4 weeks of treatment, if there are no adverse events ≥Grade 2 that are related to the study drug, then the study will proceed to the next dose level. * Cohort 3 - Three (3) patients will be enrolled at the 8mg dose level for 8 weeks of treatment. After all patients have received at least 4 weeks of treatment, if \<2 patients experience a related adverse event ≥Grade 2, then the study will proceed to the next dose level. (If ≥2 patients experience a related adverse event ≥Grade 2, the previous cohort will be expanded.) * Cohort 4 - Three (3) patients will be enrolled at the 10mg dose level for 8 weeks of treatment. After all patients have received at least 4 weeks of treatment, if \<2 patients experience a related adverse event ≥Grade 2, then the study will proceed to the next dose level. (If ≥2 patients experience a related adverse event ≥Grade 2, the previous cohort will be expanded.) * Cohort 5 - Three (3) patients will be enrolled at the 12mg dose level for 8 weeks of treatment. After all patients have received at least 4 weeks of treatment, if \<2 patients experience a related adverse event ≥Grade 2, then the study will proceed to the next dose level. (If ≥2 patients experience a related adverse event ≥Grade 2, the previous cohort will be expanded.) * Cohort 6 - Three (3) patients will be enrolled at the 16mg dose level for 8 weeks of treatment. After all patients have received at least 4 weeks of treatment, if \<2 patients experience a related adverse event ≥Grade 2, then the study will proceed to the next and final dose level. (If ≥2 patients experience a related adverse event ≥Grade 2, the previous cohort will be expanded.) * Cohort 7 - Three (3) patients will be enrolled at the 32mg dose level for 8 weeks of treatment. * An additional cohort may be explored at the 24mg dose level if deemed appropriate based on safety and activity parameters. If there are any adverse events Grade ≥2 that are related (possibly, probably, or definitely) to study drug, at the 4mg cohort or in ≥2 patients in any subsequent cohort, the dose may be reduced to the previous cohort and an additional 3-6 patients (total of up to 9) may be enrolled into that cohort. Additionally, if Hbf levels increase \>15% (expressed as a percentage of total Hb) in any cohort, the cohort can be expanded to an additional 3 to 6 patients as well as continue to the next cohort if safety parameters have been met. In the expansion cohort, patients will receive study drug treatment for an additional 4 weeks (total of 12 weeks).. Approximately 6 to 39 patients may be enrolled for the entire study. Patients are eligible to enroll in a higher cohort of the study after a minimum of one-month washout from AB1 dosing, if their HbF levels return to baseline (\<15%) and the investigator deems the patient eligible.

Conditions

• Sickle Cell Disease

Interventions

Type	Name	Description
DRUG	AB1	This will be an open-label, dose escalating study with a starting dose of 2mg. Up to 6 additional cohorts will be enrolled at subsequently higher doses of 4mg, 8mg, 10 mg, 12 mg, 16mg, and 32mg. Each dose will be taken orally, once daily, for 8 weeks

Timeline

• Start date: 2022-12-05
• Primary completion: 2024-10-01
• Completion: 2024-10-01
• First posted: 2022-03-02
• Last updated: 2024-12-04

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study