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

Tracking Information
First Submitted Date ICMJE	February 23, 2015
First Posted Date ICMJE	March 5, 2015
Last Update Posted Date	March 19, 2018
Study Start Date ICMJE	February 2015
Estimated Primary Completion Date	October 2018 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 11, 2017)	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 (16 weeks) ]
Original Primary Outcome Measures ICMJE; (submitted: March 4, 2015)	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 clinic visit, for a total of 6 weeks ]
Change History	Complete list of historical versions of study NCT02380079 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 11, 2017)	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) ]; 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) ]; 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) ]; 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) ]; 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) ]
Original Secondary Outcome Measures ICMJE; (submitted: March 4, 2015)	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 clinic visit, for a total of 8 weeks ]; 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 clinic visit, for a total of 8 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 direct bilirubin. [ Time Frame: From the time the participant is accessed at baseline through the final follow-up clinic visit, for a total of 8 weeks ]; Exploratory Outcome Measure: Change from baseline of the ex-vivo percent of red blood cells that sickle under hypoxic conditions [ Time Frame: From the time the participant is accessed at baseline through the final follow-up clinic visit, for a total of 8 weeks ]; Exploratory Outcome Measure: Change from baseline in fatigue as measured by the PROMIS fatigue questionnaire score [ Time Frame: From the time the participant is accessed at baseline through the final follow-up clinic visit, for a total of 8 weeks ]
Current Other Outcome Measures ICMJE; (submitted: April 11, 2017)	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) ]; 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) ]; 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) ]; 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) ]; 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) ]; 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) ]
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Dose-Escalation Study of SCD-101 in Sickle Cell Disease
Official Title ICMJE	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.
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.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Randomized; Intervention Model: Crossover Assignment; Intervention Model Description: 2x2 crossover Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Sickle Cell Disease; Sickle-Beta Zero Thalassemia
Intervention ICMJE	Drug: SCD-101; Administered as gelatin capsules
Study Arms	Experimental: SCD-101 SCD-101 dosed TID for 28-days Intervention: Drug: SCD-101; Placebo Comparator: Placebo Placebo dosed TID for 28-days Intervention: Drug: SCD-101
Publications *	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.; 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.; 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.; 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.; 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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: April 11, 2017)	60
Original Estimated Enrollment ICMJE; (submitted: March 4, 2015)	24
Estimated Study Completion Date	December 2018
Estimated Primary Completion Date	October 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 55 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Robert Swift, PhD 970-567-8676 sponsor@invenux.com Contact: Carolyn O' Reilly, BA 303-639-1157 carolyn@invenux.com
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT02380079
Other Study ID Numbers ICMJE	INVX-SCD-101-11
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement	Plan to Share IPD: No
Responsible Party	Invenux, LLC
Study Sponsor ICMJE	Invenux, LLC
Collaborators ICMJE	State University of New York - Downstate Medical Center
Investigators ICMJE	Principal Investigator: Peter Gillette, MD King's County Hospital
PRS Account	Invenux, LLC
Verification Date	March 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP