Dose-Escalation Study of SCD-101 in Sickle Cell Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Part A: Phase IB, Single Site, Dose-Escalation of SCD-101 and Part B: Randomized, Double-Blind, Placebo-Controlled Crossover of SCD-101 in Adults With Homozygous Sickle Cell Disease or S/Beta 0 Thalassemia.

Conditions
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Sickle Cell Disease, Sickle-Beta Zero Thalassemia

Intervention / Treatment
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* Drug: SCD-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18-55 years of age Homozygous sickle cell disease or S/beta 0 thalassemia Hemoglobin F ≤10% Hemoglobin ≥ 6.0 g/dL and ≤ 9.5 g/dL 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. Ability to adhere to the study visit schedule and other protocol requirements Ability to understand and the willingness to sign an informed consent document Exclusion Criteria: Red blood cell transfusion within 3 months of enrollment Hydroxyurea treatment within 6 months of enrollment Painful or other acute sickle cell event that required a hospitalization within 4-weeks of enrollment 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 Estimated creatinine clearance (CrCl) < 60 mL/min (Cockcroft- Gault formula) at screening. QTc interval of >470 msec at trial entry and participant with congenital long QT syndrome. No other significant sickle cell or non-sickle cell illness that would confound the results of the trial 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 Participant pregnant or nursing an infant or planning pregnancy during the course of the trial History of allergic reactions attributed to sorghum or compounds of similar chemical or biologic composition (such as Nicosan, Niprisan, Jobelyn or Xickle). Other investigational drug use within 3 months of enrollment PROMIS Fatigue Questionnaire 8a T-score ˂ 44.3

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 2x2 crossover
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCD-101<br>SCD-101 dosed TID for 28-days | Drug: SCD-101<br>* Administered as gelatin capsules<br>|
| Placebo Comparator: Placebo<br>Placebo dosed TID for 28-days | Drug: SCD-101<br>* Administered as gelatin capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Homozygous Sickle Cell Disease S/Beta 0 Thalassemia