AB1 in Adult Patients with Sickle Cell Disease (SCD)

NCT05261711 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: Pro00110179
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (2)

• Number of adverse events/serious adverse events as measured by patient report/medical records

  From the time of consent up to 12 months

• Number of ≥Grade 2 study related adverse events as measured by patient report/medical record

  Adverse events that cause enough discomfort to interfere with usual daily activity; may warrant therapeutic intervention

  From the time of consent up to 12 months

Secondary Outcomes (11)

• Change in Cmax as measured by blood test

  Baseline, week4, week8, week10

• Change in tmax as measured by blood test

  Baseline, week4, week8, week10

• Change in t1/2 as measured by blood test

  Baseline, week4, week8, week10

• Change in AUC o-t as measured by blood test

  Baseline, week4, week8, week10

• Change in dose normalized AUC o-inf as measured by blood test

  Baseline, week4, week8, week10

Study Arms (1)

AB1

EXPERIMENTAL

AB1 is the investigational product in this study taken orally, once daily, for 8 weeks. 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.

Drug: AB1

Interventions

AB1 DRUG

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

AB1

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Written, informed consent
• Age 18 to 45 years of age, inclusive at screening
• Confirmed SS or S-b0-thalassemia SCD
• Sickle crisis rate of 2-10 within the past year with no crisis in the last 28 days
• HbF \<8.6% of total Hb at screening
• Regular compliance with comprehensive care and previous therapy -

You may not qualify if:

• Experienced severe sepsis or septic shock within the previous 12 weeks
• Febrile illness in the 1 week prior to baseline visit
• Acute complications due to SCD (i.e., hospitalization, acute pain, or acute chest syndrome) in the 28 days prior to screening visit
• Plans for hospitalization, surgery, or other major procedures during the duration of the study or between screening and baseline
• ALT ≥2X the upper limit of normal or albumin \<2.0 mg/dL or direct (conjugated) bilirubin ≥ 1.5 mg/dl\*
• Serum creatinine \>2.9 mg/dL and calculated creatinine clearance \<30 mL/min# \*
• Platelet count \>800 x 109/L OR \<150 x 109/L\*
• Absolute neutrophil count \<1.5 x 109/L\*
• Currently pregnant or breastfeeding
• Female of active childbearing potential$ who is unwilling or unable to adhere to the contraception requirements specified in the protocol
• Male with female partner(s) of childbearing potential$ who is unwilling or unable to adhere to the contraception requirements specified in the protocol
• Altered mental status or recurrent seizures requiring anti-seizure medications
• Moribund or any concurrent disease (e.g., hepatic, renal, cardiac, metabolic) of such severity that death within 24 weeks is likely
• Concurrent diagnosis of malignancy including MDS, leukemia, or an abnormal karyotype
• Known Vitamin-B12, folate, or iron deficiency

Sponsors & Collaborators

• Nirmish Shah: lead

Study Sites (3)

Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Nirmish Shah, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: February 20, 2022
• First Posted: March 2, 2022
• Study Start: December 5, 2022
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: December 4, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)