A Sickle CEll Disease ComplicatioN Trial (ASCENT)

A Phase 3, Prospective, Randomized, Double-Blind, Placebo Controlled, Multi-center Study of SC411 for Sickle Cell Disease

The objective of this study is to assess the efficacy of SC411 in reducing the number of sickle cell crisis (SCC) events in sickle cell disease (SCD) subjects receiving SC411 compared to those subjects receiving placebo.

Study Overview

• Status: Unknown
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: SC411; Drug: Placebo

Detailed Description

This Phase 3, prospective, randomized, double-blinded, placebo-controlled, multi-center study will enroll approximately 210 subjects at up to 70 sites in the United States. Participation will consist of a Screening Period, followed by a minimum 12-month Treatment Period. SC411 is administered orally as a soft gel mini capsule.

This study will enroll subjects aged ≥5 to ≤17 years who have a diagnosis of SCD that includes the phenotypes hemoglobin SS homozygous (HbSS), hemoglobin SC (HbSC), and hemoglobin S/β°-thalassemia (HbS/ β°-thalassemia); and have had at least 2 but no more than 10 documented SCC events (as defined above) within 12 months prior to the Screening Visit.

• Study Type: Interventional
• Enrollment (Anticipated): 210
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Uche Sampson, MD; Phone Number: 615-678-2336; Email: usampson@micellebio.com
• Study Contact Backup: Name: George Steinfels, PhD; Phone Number: 301-742-5656; Email: gsteinfels@micellebio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients who meet all of the following criteria will be eligible to participate in the study:

1. 1. Aged ≥ 5 years and ≤ 17 years at screening;
2. Has been diagnosed with SCD (that includes the genotypes HbSS, HbSC, and HbS/β°-thalassemia, documented by hemoglobin HPLC or electrophoresis);
3. Has had between ≥ 2 to ≤10 episodes of acute SCC (as defined above) within 12 months of the Screening Visit. At least one crisis must have been managed in a hospital, clinic, or emergency room. For at least 2 of the episodes, the site must obtain the documentation created in a medical record at the time of the event.
4. Must not be receiving HU or L-Glutamine, or if receiving HU and/or L-Glutamine must be at a stable weight-based treatment regimen (mg/kg), for at least 3 months prior to the Screening Visit with the intent to continue at a weight-based dose level at the discretion of the treating physician for the duration of the study, other than for safety reasons. If taking HU and/or L-glutamine, subjects must have had at least one SCC event (as previously defined) while on HU and/or L-Glutamine.
5. Has a parent or guardian who is able to give written informed consent, and the potential pediatric subject must be able to provide assent in a manner approved by the Institutional Review Board (IRB) and comply with the requirements of the study; and
6. If post pubertal in the opinion of the Investigator, must agree to use a reliable method of birth control (e.g., barrier, birth control pills, abstinence) during the study and for 1 month following the last dose of study drug.

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from participation in the study:

1. A known allergy or hypersensitivity to fish or shellfish;
2. A known allergy or hypersensitivity to soy;
3. Inability to swallow capsules;
4. History of treatment with SC411;
5. Confirmed diagnosis of chronic pain or chronic opioid use: Defined as pain experienced ≥3 days per week over a 6-month period or daily opioid use for pain management;
6. Active infection with Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C;
7. Prothrombin time > 1.5 x ULN at screening;
8. Required regular anticoagulation or chronic aspirin therapy;
9. Moderate thrombocytopenia, defined as platelets < 80,000/µL at screening;
10. History of stroke or Moyamoya syndrome;
11. Abnormal results on most recent transcranial Doppler (TCD) evaluation;
12. Received blood transfusion or blood products in the 2 months prior to the Screening Visit or on chronic blood transfusion;
13. Chronic renal insufficiency, defined as a eGFR < 30ml/min at screening as estimated by the Schwartz equation (Appendix H), or requiring peritoneal or hemodialysis;
14. Abnormal liver function tests (ALT > 3.0 x ULN) at screening;
15. Received any organ transplant;
16. Has a recent acute illness or other concomitant chronic medical or psychiatric condition that in the opinion of the Investigator would compromise participation in the study, prevent adherence to the protocol or confound the evaluation of the study outcome;
17. Is pregnant or lactating, or has the intention of becoming pregnant during the study (if a female of child-bearing potential or partner of a female of child-bearing potential and sexually active and not willing to use an effective means of birth control);
18. Is currently taking or has been treated with any form of omega-3 fatty acid or fish oil supplement within 30 days of the Screening Visit, or intends to do so during the course of the study;
19. Has been treated with any investigational product within 30 days of the Screening Visit or intends to receive an investigational product during the course of this study; and
20. There are factors that, in the judgment of the Investigator, would make it difficult for the patient to comply with the requirements of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SC411; Omega-3 docosahexaenoic acid, soft gelatin capsule, administered once a day on a per weight basis.	Drug: SC411; Soft gelatin capsule; Other Names: Docosahexaenoic acid (DHA)
PLACEBO_COMPARATOR: Placebo; Soybean oil, soft gelatin capsule, administered once a day on a per weight basis.	Drug: Placebo; Soft gelatin capsule; Other Names: Soybean Oil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the efficacy of SC411 in reducing the number of sickle cell crisis (SCC) events in subjects compared to placebo will be measured by counting the number of sickle cell crises that occur after randomization.	Assessment of the efficacy of SC411 in reducing the number of sickle cell crisis (SCC) events in subjects compared to placebo will be measured by counting the number of sickle cell crises that occur after randomization. The primary objective of this study is to assess the efficacy of orally administered SC411 in reducing the number of sickle cell crisis (SCC) events in sickle cell disease (SCD) subjects compared to placebo. A SCC event will be defined as either an acute painful crisis or an acute chest syndrome.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the effect of SC411 compared to placebo by measuring the time until the patient's first sickle cell event.	Evaluation of days to the first event from randomization for each patient.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the the number of visits to a medical facility (hospital, clinic, or emergency room) for SCC event or complications of SCD.	Evaluation of the effect of SC411 compared to placebo by measuring the the number of visits to a medical facility (hospital, clinic, or emergency room) for SCC event or complications of SCD.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the number of days with electronic diary (eDiary)-recorded opioid or non opioid analgesic use at home to manage sickle cell pain.	To evaluate the effect of SC411 compared to placebo by measuring the number of days with electronic diary (eDiary)-recorded opioid or non opioid analgesic use at home to manage sickle cell pain.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the number of crisis-free days.	To evaluate the effect of SC411 compared to placebo by measuring the number of crisis-free days. A crisis-free day is defined as any day with a zero entry on the eDiary pain intensity scale.	52 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the effect of SC411 compared to placebo by measuring the time to second SCC event among subjects who had experienced at least one crisis while enrolled in the study.	To evaluate the effect of SC411 compared to placebo by measuring the time to second SCC event among subjects who had experienced at least one crisis while enrolled in the study.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the number of complications of SCD.	To evaluate the effect of SC411 compared to placebo by measuring the number of complications of SCD.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the Parent/guardian eDiary-recorded school attendance.	To evaluate the effect of SC411 compared to placebo by measuring the Parent/guardian eDiary-recorded school attendance.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the percent of days free of eDiary-recorded sickle cell pain out of total number of Treatment Period days.	To evaluate the effect of SC411 compared to placebo by measuring the percent of days free of eDiary-recorded sickle cell pain out of total number of Treatment Period days.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the subjects eDiary-recorded sickle cell pain score on the days that pain is recorded analyzed over time for intensity and diminution.	To evaluate the effect of SC411 compared to placebo by measuring the subjects eDiary-recorded sickle cell pain score (scale from 0-10) on the days that pain is recorded analyzed over time for intensity and diminution.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the subjects eDiary-recorded sickle cell pain score on the days during a SCC event analyzed over time for intensity and diminution.	To evaluate the effect of SC411 compared to placebo by measuring the subjects eDiary-recorded sickle cell pain score (from 0-10) on the days during a SCC event analyzed over time for intensity and diminution.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the number of hospitalization days due to SCC events.	To evaluate the effect of SC411 compared to placebo by measuring the number of hospitalization days due to SCC events. -	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the number of hospitalizations due to SCC events.	To evaluate the effect of SC411 compared to placebo by measuring the number of hospitalizations due to SCC events.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the number of acute painful crisis events.	To evaluate the effect of SC411 compared to placebo by measuring the number of acute painful crisis events.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the number of acute chest syndrome events.	To evaluate the effect of SC411 compared to placebo by measuring the number of acute chest syndrome events.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the number of simple and exchange blood transfusions.	To evaluate the effect of SC411 compared to placebo by measuring the number of simple and exchange blood transfusions.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in hemoglobin.	To evaluate the effect of SC411 compared to placebo by measuring the changes in hemoglobin.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in hematocrit.	To evaluate the effect of SC411 compared to placebo by measuring the changes in hematocrit.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in hemoglobin phenotype.	To evaluate the effect of SC411 compared to placebo by measuring the changes in hemoglobin phenotype.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in white blood cells.	To evaluate the effect of SC411 compared to placebo by measuring the changes in white blood cells.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in blood platelets.	To evaluate the effect of SC411 compared to placebo by measuring the changes in blood platelets.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in the RBC membrane omega-3 fatty acids index.	To evaluate the effect of SC411 compared to placebo by measuring the changes in the RBC membrane omega-3 fatty acids index (arachidonic acid, docosahexaenoic acid, and eicosapentaenoic acid).	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in the reticulocyte count.	To evaluate the effect of SC411 compared to placebo by measuring the changes in the reticulocyte count.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in lactate dehydrogenase.	To evaluate the effect of SC411 compared to placebo by measuring the changes in lactate dehydrogenase.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in haptoglobin.	To evaluate the effect of SC411 compared to placebo by measuring the changes in haptoglobin.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in indirect bilirubin.	To evaluate the effect of SC411 compared to placebo by measuring the changes in indirect bilirubin.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in high sensitivity C-reactive protein.	To evaluate the effect of SC411 compared to placebo by measuring the changes in high sensitivity C-reactive protein.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in D-dimer.	To evaluate the effect of SC411 compared to placebo by measuring the changes in D-dimer.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in whole blood adhesion to vascular cell adhesion molecule-1.	To evaluate the effect of SC411 compared to placebo by measuring the changes in whole blood adhesion to vascular cell adhesion molecule-1.	52 weeks
Evaluation of the effect of SC411 compared to placebo by measuring the changes in E-selectin.	To evaluate the effect of SC411 compared to placebo by measuring the changes in E-selectin.	52 weeks

Collaborators and Investigators

• Sponsor: Micelle BioPharma Inc
• Investigators: Study Chair: Carton Dampier, MD, Emory University; Study Chair: Matt Heeney, MD, Harvard University; Study Chair: Beng Fuh, MD, East Carolina University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2019
• Primary Completion (ANTICIPATED): December 1, 2020
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: November 11, 2015
• First Submitted That Met QC Criteria: November 12, 2015
• First Posted (ESTIMATE): November 13, 2015

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2019
• Last Update Submitted That Met QC Criteria: January 30, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: hemoglobin SS; hemoglobin SC; hemoglobin S/β°-thalassemia
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: OMEG-411-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No