Sickle Cell DiseasePhase 1/2(SCD)NCT05261711
AB1 in Adult Patients With Sickle Cell Disease (SCD)
A Phase 1/2 study testing AB1 in people with Sickle Cell Disease, run by Nirmish Shah at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- AB1
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 3 sitesUnited States
- Study dates
- 5 Dec 2022to 1 Oct 2024
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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 -
Who cannot join
- 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# *
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- 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
- New York Heart Association (NYHA) class III/IV status
- Eastern Co-operative Oncology Group (ECOG) performance status ≥3
- Participant is on chronic transfusion therapy (e.g., for history of TIA or stroke) and medically contraindicated to discontinue transfusions (unless multiple allo-antibodies prevent the patient from getting transfusions as scheduled)
- Blood transfusion in the 28 days prior to screening visit or between screening and baseline visits
- Known history of illicit drug or alcohol abuse within the past 12 months.
- Current treatment with Oxbryta or Adakveo (must be off therapy for 30 days for Oxbryta with no plans to restart and off therapy for 3 months for Adakveo with no plans to restart)
- Other experimental or investigational drug therapy in the past 28 days -
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Augusta University Medical Center
Augusta, Georgia, 30912
Duke University Medical Center
Durham, North Carolina, 27710
East Carolina University
Greenville, North Carolina, 27834
About this study
Official title: 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)
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.
Read the 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
- Being tested
- AB1
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AB1Drug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: AB1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Adverse Events/Serious Adverse Events as Measured by Patient Report/Medical Records
Measured: From the time of consent up to 12 months
Number of Participants With ≥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
Measured: From the time of consent up to 12 months
Secondary outcomes (11)
Change in Cmax as Measured by Blood Test
Cmax is defined as the highest concentration a drug achieves in the bloodstream.
Measured: Baseline, week 4, week 8, week 10
Change in Tmax as Measured by Blood Test
Tmax is defined as the time required to reach Cmax.
Measured: Baseline, week 4, week 8, week 10
Change in T1/2 (Half Life) as Measured by Blood Test
T1/2 (half life) is defined as the time required for the plasma concentration of a drug to decrease by half during the elimination phase.
Measured: Baseline, week 4, week 8, week 10
Change in AUC O-t as Measured by Blood Test
AUC o-t (Area Under the Curve from time zero to the last measurable concentration) measures a drug's total exposure in the bloodstream over a specific duration.
Measured: Baseline, week 4, week 8, week 10
Change in Dose Normalized AUC O-inf as Measured by Blood Test
AUC o-inf (Area Under the Curve from time zero to infinity) is a vital metric that quantifies total drug exposure in the bloodstream. It represents the total amount of an administered drug that enters systemic circulation, from the moment it is given until it is completely eliminated from the body.
Measured: Baseline, week 4, week 8, week 10
Change in Clearance (CL) as Measured by Blood Test
Clearance (CL) is the fundamental parameter measuring how efficiently the body removes a drug from systemic circulation. It represents the volume of plasma completely cleared of a drug per unit of time.
Measured: Baseline, week 4, week 8, week 10
Change in Volume of Distribution (Vz) as Measured by Blood Test
Volume of distribution (Vz) represents the apparent volume of distribution during the terminal phase. It relates the amount of drug in the body to the plasma concentration specifically during the drug's elimination phase.
Measured: Baseline, week 4, week 8, week 10
Change in Vss (Volume of Distribution at Steady State) as Measured by Blood Test
Vss (Volume of Distribution at Steady State) is a core pharmacokinetic parameter that defines the theoretical volume a drug would occupy if it were uniformly distributed at its steady-state concentration. It represents the actual blood and tissue volume the drug penetrates without being skewed by the terminal elimination phase.
Measured: Baseline, week 4, week 8, week 10
Change in Percentage of Total Percentage of Total Hemoglobin (HB) as Measured by HPLC (High-Performance Liquid Chromatography)
Reported as the percent change from baseline to week 10.
Measured: Screening, baseline, week 2, week 4, week 6, week 8, week 10, week 12
Change in Percentage of F-cells Measured by Flow Cytometry
Reported as the percent change from baseline to week 10.
Measured: Screening, baseline, week 2,week 4, week 6, week 8, week 10, week 12
Change in Percent Reticulocytes as Measured by Blood Tests
Measured: Screening, baseline, week 2,week 4, week 6, week 8, week 10, week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2022
- Study start5 Dec 2022
- Primary completion1 Oct 2024
- Study completion1 Oct 2024
Why it stopped: Study is terminated prior to its planned completion as anticipated by the protocol due to enrollment completion. Data clean up and analysis is being performed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nirmish Shah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nirmish Shah, Duke University
- Investigators
- Nirmish Shah, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05261711
- Sponsor's protocol ID
- Pro00110179
- Acronym
- (SCD)
- Status last verified
- Sep 2026
- First submitted
- 20 Feb 2022
- Last updated
- 15 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No