## Protocol Section
### Identification Module
**NCT ID:** 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.

#### Organization Study ID Info
**ID:** INVX-SCD-101-11
#### Organization
**Class:** INDUSTRY
**Full Name:** Invenux, LLC
### Status Module
#### Completion Date
**Date:** 2023-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-03-21

**Type:** ACTUAL

**Last Update Submit Date:** 2023-03-20

**Overall Status:** ACTIVE_NOT_RECRUITING

#### Primary Completion Date
**Date:** 2023-11

**Type:** ESTIMATED

#### Start Date
**Date:** 2015-02

**Type:** ACTUAL

**Status Verified Date:** 2023-03

#### Study First Post Date
**Date:** 2015-03-05
**Type:** ESTIMATED
**Study First Submit Date:** 2015-02-23
**Study First Submit QC Date:** 2015-03-04
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** State University of New York - Downstate Medical Center

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Invenux, LLC

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Sickle Cell Disease

- Sickle-Beta Zero Thalassemia

**Keywords:**

- Homozygous Sickle Cell Disease S/Beta 0 Thalassemia

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

**Intervention Model Description:** 2x2 crossover

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** SCD-101 dosed TID for 28-days

**Intervention Names:**

- Drug: SCD-101

**Label:** SCD-101

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Placebo dosed TID for 28-days

**Intervention Names:**

- Drug: SCD-101

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Placebo

- SCD-101

**Description:** Administered as gelatin capsules

**Name:** SCD-101

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Measure:** 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)

**Measure:** 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)

**Measure:** 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)

**Measure:** 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)

**Measure:** 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)

**Measure:** 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)

#### Primary Outcomes

**Measure:** 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 Outcomes

**Measure:** 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)

**Measure:** 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)

**Measure:** 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)

**Measure:** 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)

**Measure:** 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)

**Measure:** 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)

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 55 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Brooklyn

**Country:** United States

**Facility:** King's County Hospital

**State:** New York

**Zip:** 11203

#### Overall Officials

**Official 1:**

**Affiliation:** King's County Hospital

**Name:** John Muthu, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**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.

**PMID:** 11515714

**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.

**PMID:** 12100171

**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.

**PMID:** 12956772

**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.

**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.

**PMID:** 28096387

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000000745

- Term: Anemia, Hemolytic, Congenital

- ID: D000000743

- Term: Anemia, Hemolytic

- ID: D000000740

- Term: Anemia

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000006453

- Term: Hemoglobinopathies

- ID: D000030342

- Term: Genetic Diseases, Inborn

### Condition Browse Module - Browse Branches

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16557

- Name: Thalassemia

- Relevance: HIGH

- As Found: Thalassemia

- ID: M4085

- Name: Anemia, Sickle Cell

- Relevance: HIGH

- As Found: Sickle Cell Disease

- ID: M4070

- Name: Anemia

- Relevance: LOW

- As Found: Unknown

- ID: M9547

- Name: Hemolysis

- Relevance: LOW

- As Found: Unknown

- ID: M4073

- Name: Anemia, Hemolytic

- Relevance: LOW

- As Found: Unknown

- ID: M4075

- Name: Anemia, Hemolytic, Congenital

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9539

- Name: Hemoglobinopathies

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: T5622

- Name: Thalassemia

- Relevance: HIGH

- As Found: Thalassemia

- ID: T5229

- Name: Sickle Cell Anemia

- Relevance: HIGH

- As Found: Sickle Cell Disease

### Condition Browse Module - Meshes

- ID: D000000755

- Term: Anemia, Sickle Cell

- ID: D000013789

- Term: Thalassemia

### Misc Info Module

- Version Holder: 2024-05-24
