Sickle-Beta Zero Thalassemia, Sickle Cell Disease
Conditions
Keywords
Homozygous Sickle Cell Disease S/Beta 0 Thalassemia
Brief summary
The purpose of this study is to determine the safety and clinical effects of SCD-101 when given to adults with sickle cell disease.
Detailed description
This is single site, dose- escalation study of SCD-101 in participants with homozygous sickle cell disease (S/S) or S/beta 0 Thalassemia. All participants will be monitored for safety, tolerability, and dose-limiting toxicities. The study is divided into two parts. Part A is an open-label, non-randomized, non-placebo-controlled dose escalation study with a 28-day treatment phase and 14-day follow-up phase with five cohorts . Part B is a randomized, placebo-controlled, confirmatory 2x2 crossover cohort with a 28 day washout between periods, and a 28-day follow-up phase.
Interventions
DRUGSCD-101
Administered as gelatin capsules
Sponsors
State University of New York - Downstate Medical Center
Invenux, LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
2x2 crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, 18-55 years of age 2. Homozygous sickle cell disease or S/beta 0 thalassemia 3. Hemoglobin F ≤10% 4. Hemoglobin ≥ 6.0 g/dL and ≤ 9.5 g/dL 5. Female participants of child bearing potential and male participants whose partner is a female of child bearing potential must be willing to use approved contraception during the trial and for 3 months following the end of treatment. Only barrier methods or complete abstinence are acceptable for this study. Participants using hormonal contraception (including morning-after-pill) and IUD are excluded unless willing/able to change to an acceptable form of contraception. 6. Ability to adhere to the study visit schedule and other protocol requirements 7. Ability to understand and the willingness to sign an informed consent document
Exclusion criteria
1. Red blood cell transfusion within 3 months of enrollment 2. Hydroxyurea treatment within 6 months of enrollment 3. Painful or other acute sickle cell event that required a hospitalization within 4-weeks of enrollment 4. AST and/or ALT \>3x upper limit of normal and/or creatinine \>2x upper limit of normal or any other significant renal or hepatic impairment 5. Estimated creatinine clearance (CrCl) \< 60 mL/min (Cockcroft- Gault formula) at screening. 6. QTc interval of \>470 msec at trial entry and participant with congenital long QT syndrome. 7. No other significant sickle cell or non-sickle cell illness that would confound the results of the trial 8. Any condition that, in the view of the investigator, places the participant at risk because of participation in the trial, or may influence the result of the trial or the participant's ability to participate in the trial 9. Participant pregnant or nursing an infant or planning pregnancy during the course of the trial 10. History of allergic reactions attributed to sorghum or compounds of similar chemical or biologic composition (such as Nicosan, Niprisan, Jobelyn or Xickle). 11. Other investigational drug use within 3 months of enrollment 12. PROMIS Fatigue Questionnaire 8a T-score ˂ 44.3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine the safety, tolerability, and dose limiting toxicities of escalating doses of SCD-101, assessed by frequency and severity of adverse events (AEs), and changes in vital signs, 12-lead ECGs and laboratory assessments as compared to baseline | From the time the participant is administered the first dose through the final follow-up (18 weeks) |
Secondary
| Measure | Time frame |
|---|---|
| Determine the effect of escalating doses of SCD-101 on the mean change in hemoglobin form base line | From the time the participant is accessed at baseline through the final follow-up (18 weeks) |
| Determine the effect of escalating doses of SCD-101 on the mean change in percent reticulocytes from baseline | From the time the participant is accessed at baseline through the final follow-up (18 weeks) |
| Determine the effect of escalating doses of SCD-101 on the mean change from baseline in red blood cell hemolysis as measured by lactate dehydrogenase (LDH) and indirect bilirubin. | From the time the participant is accessed at baseline through the final follow-up (18 weeks) |
| Determine the effect of escalating doses of SCD-101 on the mean change from baseline in fatigue as measured by the PROMIS fatigue questionnaire | From the time the participant is accessed at baseline through the final follow-up (18 weeks) |
| Determine the effect of escalating doses of SCD-101 on the mean change from baseline in the percent of venous circulating sickle red blood cells | From the time the participant is accessed at baseline through the final follow-up (18 weeks) |
| Determine the effect of escalating doses of SCD-101 on the mean change from baseline in functional capacity as measured by the 6-Minute Walk Test | From the time the participant is accessed at baseline through the final follow-up (18 weeks) |
Other
| Measure | Time frame |
|---|---|
| Part B: Exploratory Outcome Measure the mean change from baseline in pain interference as measured by the PROMIS pain interference questionnaire | From the time the participant is accessed at baseline through the final follow-up (18 weeks) |
| Part B: Exploratory Outcome Measure the mean change from baseline in patient reported daily pain as measured by a Numeric Rating Scale (NRS 0-10) | From the time the participant is accessed at baseline through the final follow-up (18 weeks) |
| Part B: Exploratory Outcome Measure the mean change from baseline in analgesic usage as measured by patient medication diary | From the time the participant is accessed at baseline through the final follow-up (18 weeks) |
| Part B: Exploratory Outcome Measure the mean:change from baseline in exercise and sleep activity as measured by wrist actigraphy | From the time the participant is accessed at baseline through the final follow-up (18 weeks) |
| Part B: Exploratory Outcome Measure the mean:change from baseline in plasma inflammatory cytokines as measured by ELISA | From the time the participant is accessed at baseline through the final follow-up (18 weeks) |
| Part B: Exploratory Outcome Measure the mean change from baseline in sleep interference as measured by the PROMIS sleep interference questionnaire | From the time the participant is accessed at baseline through the final follow-up (18 weeks) |
Countries
United States
Outcome results
None listed