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

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.

The purpose of this study is to determine the safety and clinical effects of SCD-101 when given to adults with sickle cell disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Sickle Cell Disease; Sickle-Beta Zero Thalassemia
• Intervention / Treatment: Drug: SCD-101

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: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Robert Swift, PhD; Phone Number: 970-206-4622; Email: sponsor@invenux.com
• Study Contact Backup: Name: Carolyn O' Reilly, BA; Phone Number: 303-639-1157; Email: carolyn@invenux.com

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11203
      • King's County Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SCD-101; SCD-101 dosed TID for 28-days	Drug: SCD-101; Administered as gelatin capsules
Placebo Comparator: Placebo; Placebo dosed TID for 28-days	Drug: SCD-101; Administered as gelatin capsules

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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)
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)

Collaborators and Investigators

• Sponsor: Invenux, LLC
• Collaborators: State University of New York - Downstate Medical Center
• Investigators: Principal Investigator: John Muthu, MD, King's County Hospital

Publications and helpful links

General 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. doi: 10.1078/0944-7113-00040.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: February 23, 2015
• First Submitted That Met QC Criteria: March 4, 2015
• First Posted (Estimate): March 5, 2015

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Homozygous Sickle Cell Disease S/Beta 0 Thalassemia
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Thalassemia
• Other Study ID Numbers: INVX-SCD-101-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No