Back to resultsDose-Escalation Study of SCD-101 in Sickle Cell Disease
Primary Purpose
Sickle Cell Disease, Sickle-Beta Zero Thalassemia
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SCD-101
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease focused on measuring Homozygous Sickle Cell Disease S/Beta 0 Thalassemia
Eligibility Criteria
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
Sites / Locations
- King's County Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
SCD-101
Placebo
Arm Description
SCD-101 dosed TID for 28-days
Placebo dosed TID for 28-days
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Determine the effect of escalating doses of SCD-101 on the mean change in hemoglobin form base line
Determine the effect of escalating doses of SCD-101 on the mean change in percent reticulocytes from baseline
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.
Determine the effect of escalating doses of SCD-101 on the mean change from baseline in fatigue as measured by the PROMIS fatigue questionnaire
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
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
Full Information
NCT ID
NCT02380079
First Posted
February 23, 2015
Last Updated
March 20, 2023
Sponsor
Invenux, LLC
Collaborators
State University of New York - Downstate Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT02380079
Brief Title
Dose-Escalation Study of SCD-101 in Sickle Cell Disease
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 2015 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Invenux, LLC
Collaborators
State University of New York - Downstate Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease, Sickle-Beta Zero Thalassemia
Keywords
Homozygous Sickle Cell Disease S/Beta 0 Thalassemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
2x2 crossover
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
SCD-101
Arm Type
Experimental
Arm Description
SCD-101 dosed TID for 28-days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo dosed TID for 28-days
Intervention Type
Drug
Intervention Name(s)
SCD-101
Intervention Description
Administered as gelatin capsules
Primary Outcome Measure Information:
Title
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
Time Frame
From the time the participant is administered the first dose through the final follow-up (18 weeks)
Secondary Outcome Measure Information:
Title
Determine the effect of escalating doses of SCD-101 on the mean change in hemoglobin form base line
Time Frame
From the time the participant is accessed at baseline through the final follow-up (18 weeks)
Title
Determine the effect of escalating doses of SCD-101 on the mean change in percent reticulocytes from baseline
Time Frame
From the time the participant is accessed at baseline through the final follow-up (18 weeks)
Title
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.
Time Frame
From the time the participant is accessed at baseline through the final follow-up (18 weeks)
Title
Determine the effect of escalating doses of SCD-101 on the mean change from baseline in fatigue as measured by the PROMIS fatigue questionnaire
Time Frame
From the time the participant is accessed at baseline through the final follow-up (18 weeks)
Title
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
Time Frame
From the time the participant is accessed at baseline through the final follow-up (18 weeks)
Title
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
Time Frame
From the time the participant is accessed at baseline through the final follow-up (18 weeks)
Other Pre-specified Outcome Measures:
Title
Part B: Exploratory Outcome Measure the mean change from baseline in sleep interference as measured by the PROMIS sleep interference questionnaire
Time Frame
From the time the participant is accessed at baseline through the final follow-up (18 weeks)
Title
Part B: Exploratory Outcome Measure the mean change from baseline in pain interference as measured by the PROMIS pain interference questionnaire
Time Frame
From the time the participant is accessed at baseline through the final follow-up (18 weeks)
Title
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)
Time Frame
From the time the participant is accessed at baseline through the final follow-up (18 weeks)
Title
Part B: Exploratory Outcome Measure the mean change from baseline in analgesic usage as measured by patient medication diary
Time Frame
From the time the participant is accessed at baseline through the final follow-up (18 weeks)
Title
Part B: Exploratory Outcome Measure the mean:change from baseline in exercise and sleep activity as measured by wrist actigraphy
Time Frame
From the time the participant is accessed at baseline through the final follow-up (18 weeks)
Title
Part B: Exploratory Outcome Measure the mean:change from baseline in plasma inflammatory cytokines as measured by ELISA
Time Frame
From the time the participant is accessed at baseline through the final follow-up (18 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Muthu, MD
Organizational Affiliation
King's County Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
King's County Hospital
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
11515714
Citation
Wambebe C, Khamofu H, Momoh JA, Ekpeyong M, Audu BS, Njoku OS, Bamgboye EA, Nasipuri RN, Kunle OO, Okogun JI, Enwerem MN, Audam JG, Gamaniel KS, Obodozie OO, Samuel B, Fojule G, Ogunyale O. Double-blind, placebo-controlled, randomised cross-over clinical trial of NIPRISAN in patients with Sickle Cell Disorder. Phytomedicine. 2001 Jul;8(4):252-61. doi: 10.1078/0944-7113-00040.
Results Reference
background
PubMed Identifier
12100171
Citation
Iyamu EW, Turner EA, Asakura T. In vitro effects of NIPRISAN (Nix-0699): a naturally occurring, potent antisickling agent. Br J Haematol. 2002 Jul;118(1):337-43. doi: 10.1046/j.1365-2141.2002.03593.x.
Results Reference
background
PubMed Identifier
12956772
Citation
Iyamu EW, Turner EA, Asakura T. Niprisan (Nix-0699) improves the survival rates of transgenic sickle cell mice under acute severe hypoxic conditions. Br J Haematol. 2003 Sep;122(6):1001-8. doi: 10.1046/j.1365-2141.2003.04536.x.
Results Reference
background
Citation
Swift, RA, Nathan, S, Tripathi, P, Chen, Q, Asakura,T (2009, September). Research Preview on Improving Nicosan™/Xickle™: A Phyto-Medicine for the Treatment of Sickle Cell Disease. Paper presented at the meeting of the Sickle Cell Disease Association of America, Orlando, FL.
Results Reference
background
PubMed Identifier
28096387
Citation
Li Q, Henry ER, Hofrichter J, Smith JF, Cellmer T, Dunkelberger EB, Metaferia BB, Jones-Straehle S, Boutom S, Christoph GW, Wakefield TH, Link ME, Staton D, Vass ER, Miller JL, Hsieh MM, Tisdale JF, Eaton WA. Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease. Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E689-E696. doi: 10.1073/pnas.1619054114. Epub 2017 Jan 17.
Results Reference
derived
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Dose-Escalation Study of SCD-101 in Sickle Cell Disease
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