Back to resultsAB1 in Adult Patients With Sickle Cell Disease (SCD) ((SCD))
Primary Purpose
Sickle Cell Disease
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AB1
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease
Eligibility Criteria
Inclusion Criteria:
- 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 -
Exclusion Criteria:
- 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
- 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 -
Sites / Locations
- Augusta University Medical CenterRecruiting
- Duke University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AB1
Arm Description
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 with additional cohorts enrolled at subsequently higher doses of 4mg, 8mg, 16mg, and 32mg.
Outcomes
Primary Outcome Measures
Number of adverse events/serious adverse events as measured by patient report/medical records
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
Secondary Outcome Measures
Change in Cmax as measured by blood test
Change in tmax as measured by blood test
Change in t1/2 as measured by blood test
Change in AUC o-t as measured by blood test
Change in dose normalized AUC o-inf as measured by blood test
Change in CL as measured by blood test
Change in Vz as measured by blood test
Change in Vss as measured by blood test
Change in percentage of total percentage of total hemoglobin (HB) as measured by HPLC
Change in percentage of F-cells measured by flow cytometry
Change in percent reticulocytes as measured by blood tests
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05261711
Brief Title
AB1 in Adult Patients With Sickle Cell Disease (SCD)
Acronym
(SCD)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 5, 2022 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Nirmish Shah
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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. 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 1 that are related (possibly, probably, or definitely) to the study drug, then the study will proceed to the next dose level.
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 1 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 1, then the study will proceed to the next dose level.
Cohort 4 - 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 1, then the study will proceed to the next and final dose level.
Cohort 5 - Three (3) patients will be enrolled at the 32mg dose level for 8 weeks of treatment.
Additional cohorts may be explored at 12 and 24mg dose levels if deemed appropriate based on safety and activity parameters.
If there are any adverse events >Grade 1 that are related (possibly, probably, or definitely) to study drug, at the 4mg cohort or >2 patients in any subsequent cohort, the dose may be decreased to that for the previous cohort and an additional 3 patients (up to a total of 5 or 6) may be enrolled into that previous cohort. Additionally, if HbF levels, as a percent of total Hb, increase to >15% in any cohort, the cohort can be expanded by an additional 3 patients, as well as continuing to the next cohort if safety parameters have been met.
Approximately 6 to 30 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 (<8.6%) and the investigator deems the patient eligible.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model 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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AB1
Arm Type
Experimental
Arm Description
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 with additional cohorts enrolled at subsequently higher doses of 4mg, 8mg, 16mg, and 32mg.
Intervention Type
Drug
Intervention Name(s)
AB1
Intervention 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. Each dose will be taken orally, once daily, for 8 weeks
Primary Outcome Measure Information:
Title
Number of adverse events/serious adverse events as measured by patient report/medical records
Time Frame
From the time of consent up to 12 months
Title
Number of ≥Grade 2 study related adverse events as measured by patient report/medical record
Description
Adverse events that cause enough discomfort to interfere with usual daily activity; may warrant therapeutic intervention
Time Frame
From the time of consent up to 12 months
Secondary Outcome Measure Information:
Title
Change in Cmax as measured by blood test
Time Frame
Baseline, week4, week8, week10
Title
Change in tmax as measured by blood test
Time Frame
Baseline, week4, week8, week10
Title
Change in t1/2 as measured by blood test
Time Frame
Baseline, week4, week8, week10
Title
Change in AUC o-t as measured by blood test
Time Frame
Baseline, week4, week8, week10
Title
Change in dose normalized AUC o-inf as measured by blood test
Time Frame
Baseline, week4, week8, week10
Title
Change in CL as measured by blood test
Time Frame
Baseline, week4, week8, week10
Title
Change in Vz as measured by blood test
Time Frame
Baseline, week4, week8, week10
Title
Change in Vss as measured by blood test
Time Frame
Baseline, week4, week8, week10
Title
Change in percentage of total percentage of total hemoglobin (HB) as measured by HPLC
Time Frame
Screening, baseline, week2,week4, week6, week8, week10, week12
Title
Change in percentage of F-cells measured by flow cytometry
Time Frame
Screening, baseline, week2,week4, week6, week8, week10, week12
Title
Change in percent reticulocytes as measured by blood tests
Time Frame
Screening, baseline, week2,week4, week6, week8, week10, week12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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 -
Exclusion Criteria:
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
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 -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nirmish Shah, MD
Phone
919-668-5128
Email
nirmish.shah@duke.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Lindsey Muller
Phone
919-684-6180
Email
lindsey.muller@duke.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nirmish Shah, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Augusta University Medical Center
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Girindra Raval, MBBS
Phone
706-721-2505
Email
GRAVAL1@augusta.edu
First Name & Middle Initial & Last Name & Degree
LaTanya Bowman, RN, BSN
Phone
(706) 723-4332
Email
LBOWMAN@augusta.edu
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nirmish Shah, MD
Phone
919-668-5178
Email
nirmish.shah@duke.edu
First Name & Middle Initial & Last Name & Degree
Lindsey Muller
Phone
919-684-6180
Email
lindsey.muller@duke.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
AB1 in Adult Patients With Sickle Cell Disease (SCD)
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