Efficacy and Safety of SIL-8301 for Control of Hemolysis in a Uniform Sickle Cell Disease Endotype (RESCUE)

A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Determine Efficacy and Safety of SIL-8301 in Sickle Cell Disease (SCD) Patients With a Predominantly Hemolytic Phenotype

SIL-8301 (senicapoc) is being developed for the chronic treatment of patients with sickle cell disease in both adults and children. The purpose of this study is to compare the effects of senicapoc to placebo in patients with sickle cell disease that have had fewer than 2 acute sickle-related painful crises per year over the preceding 2 years, and have a predominantly hemolytic phenotype, defined as presence or history of at least one hemolytic complication and a baseline Hb of 9 g/dL or less, despite receiving hydroxyurea (an oral drug used for treatment of sickle cell disease) as standard of care. Participants will take senicapoc or matching placebo daily and continue on hydroxyurea as prescribed for up to 24 weeks.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease; Sickle Cell Anemia; Sickle Cell Anaemia
• Intervention / Treatment: Drug: Senicapoc; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Head of Clinical Operations; Phone Number: (978) 245-7397; Email: trials@biossil.ai

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Recruiting
      • The Hospital for Sick Children
    • Toronto, Ontario, Canada
      • Not yet recruiting
      • University Health Network, Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada
      • Not yet recruiting
      • McGill University Health Centre
    • Montreal, Quebec, Canada
      • Not yet recruiting
      • Centre Hospitalier de l'Université de Montréal (CHUM)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented diagnosis of sickle cell disease
• 16-35 years of age
• Hb ≤ 9.0 g/dL
• History of no more than 1 acute SCD-related painful crises requiring a visit to a medical facility per year within the preceding 2 years
• History of at least one hemolytic complication
• Current treatment with hydroxyurea

Exclusion Criteria:

• Receipt of senicapoc in a previous investigational study
• Current Red Blood Cell (RBC) transfusion or exchange transfusion program
• History of pulmonary hypertension
• Active cardiovascular, neurologic, endocrine, hepatic, or renal disorders
• Diagnosis of cancer (except non-melanoma skin cancer in situ, cervical cancer in situ, or breast cancer in situ) within the last 5 years
• History of liver disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Senicapoc (SIL-8301); 20 mg twice daily for 4 days, followed by 10 mg once daily for up to 24 weeks	Drug: Senicapoc; 10 mg tablets; administered at a loading dose of 20 mg twice daily for 4 days, followed by a maintenance dose of 10 mg once daily for up to 24 weeks; Other Names: SIL-8301
Placebo Comparator: Placebo; Matching placebo tablets twice daily for 4 days, followed by once daily for up to 24 weeks	Drug: Placebo; Tablets similar in size and color; matching administration schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hb response rate	Proportion of participants achieving an increase in Hb of > 1 g/dL from baseline	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with a Hb increase of > 2g/dL from baseline		24 Weeks
Percent change from baseline in urine albumin-creatinine ratio (uACR)		24 Weeks
Change from baseline in the 6-minute walk test (6mwt)		24 Weeks
Sickle cell disease complication rate	Proportion of participants experiencing at least one new or worsening hemolytic complication at any time during the study	24 Weeks
Proportion of participants with at least one category of improvement from baseline in Clinician and Patient Global Impression of Change		24 Weeks
Frequency of acute sickle cell-related painful crises		28 Weeks
Incidence of AEs, SAEs, and sickle cell disease related AEs		28 Weeks
Change from baseline in Hb (g/dL)		24 Weeks
Change from baseline in lactate dehydrogenase (LDH) (u/L)		24 Weeks
Change from baseline in indirect bilirubin (µmol/L)		24 Weeks
Change from baseline in reticulocyte count (%)		24 Weeks
Change from baseline in participant reported quality of life assessment overall score and subscale domain scores of the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-ME)	The ASCQ-ME is a patient-reported outcome measurement system that evaluates and monitors the physical, mental, and social well-being of patients with SCD. For each subscale, there are 5 questions using a 5 point Likert scale. Scores for each subscale range from 0 to 100, where lower scores connote worse disease impact.	24 Weeks
Change from baseline in overall score and subscale domain scores of the Participant-Reported Outcomes Measurement Information System (PROMIS)	The PROMIS-29 assessment for adult participants assesses depressive symptoms, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities. The PROMIS Pediatric-25 assessment for participants <18 years of age assesses depressive symptoms, anxiety, physical function and mobility, pain interference, fatigue, and peer relationships. For both PROMIS assessments, a higher score indicates worse symptoms except for higher physical function values which indicate better physical function.	24 Weeks

Collaborators and Investigators

• Sponsor: Biossil Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): August 13, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: November 13, 2025
• First Submitted That Met QC Criteria: December 1, 2025
• First Posted (Actual): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): August 17, 2026
• Last Update Submitted That Met QC Criteria: August 13, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Anemia; Hematologic Diseases; Genetic Diseases, Inborn; Anemia, Sickle Cell; Hemoglobinopathies; Anemia, Hemolytic; senicapoc; Hemic and Lymphatic Diseases; Anemia, Hemolytic, Congenital; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Anaemia, Sickle Cell
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Anemia, Sickle Cell; Anemia; Hematologic Diseases; Hemoglobinopathies; Anemia, Hemolytic; Anemia, Hemolytic, Congenital; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; senicapoc
• Other Study ID Numbers: SIL-8301-001

Drug and device information, study documents

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