Dose-Finding Study of SC411 in Children With Sickle Cell Disease

Status: Recruiting
Phase:
DFCI Protocol ID:

This is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study of SC411 in children with sickle cell disease (SCD). The primary objective of the study is to evaluate the safety and tolerability of three different doses of SC411 compared to a placebo. All patients will undergo eight weeks of oral study treatment and a four-week safety follow-up period. Patients will be randomized to one of three dose levels of SC411 or placebo.

Conducting Institutions:

Children's Hospital Boston, Dana-Farber Cancer Institute

Overall PI:

Matthew Heeney, MD, Children's Hospital Boston

Site-responsible Investigators:

Contacts:

Children's Hospital Boston: Ashley Cronkright, Ashley.Cronkright@childrens.harvard.edu

Eligibility Criteria

Inclusion Criteria:

  1. Aged greater than or equal to 5 years and less than or equal to 17 years at
     screening;

  2. Has been diagnosed with SCD that includes the genotypes HbSS, hemoglobin SC, and
     HbS/beta-thalassemia. Hemoglobin genotyping must be previously documented by either
     hemoglobin high-performance liquid chromatography [HPLC] or electrophoresis at time
     of Screening. If a patient does not have documented hemoglobin genotyping at the time
     of Screening, or has received a blood transfusion within the two months prior to the
     Screening Visit, hemoglobin genotyping should be documented by hemoglobin HPLC;

  3. Has had at least two and no more than ten documented episodes of clinical sickle cell
     crises within 12 months prior to the Screening Visit. A sickle cell crisis is defined
     as an episode of vaso-occlusive event:

       -  Painful crisis defined as new onset of pain that lasts two or more hours for
  which there is no explanation other than vaso-occlusion, and which requires
  therapy with oral or parenteral opioids, non-steroidal anti-inflammatory drugs,
  or other analgesics prescribed by a healthcare provider in a medical setting
  such as a hospital, clinic, or emergency room visit, or documented telephone
  management (Ballas, 2010; Heeney, 2016; Jacob, 2005); and

       -  Acute chest syndrome defined as acute illness characterized by a new segmental
  pulmonary infiltrate on a chest x-ray, and fever (greater than or equal to
  38.5°C) or respiratory symptoms such as hypoxia, chest pain, tachypnea,
  wheezing, or cough (Ballas, 2010);

  4. Is either not on hydroxyurea at the Screening Visit and does not plan on receiving it
     during the course of the study or has received hydroxyurea for a minimum of 6 months
     and, except for safety reasons, will remain on the same weight-based dose of
     hydroxyurea from screening throughout the duration of the study;

  5. Parent or guardian is able to give written informed consent, and the potential
     pediatric patient is able to provide assent in a manner approved by the Institutional
     Review Board (IRB) and comply with the requirements of the study other than for
     safety reasons; and

  6. If sexually active, agrees to use a reliable method of birth control (eg, barrier,
     birth control pills, abstinence) during the study and for one month following the
     last dose of study drug.

Exclusion Criteria:

  1. Has a significant medical condition that required hospitalization (other than sickle
     cell crisis) within two months of the Screening Visit;

  2. Has a known allergy or hypersensitivity to fish or shellfish;

  3. Has a known allergy or hypersensitivity to soy;

  4. Is planning to initiate, terminate, or alter the dosing of hydroxyurea while on
     study, other than for safety reasons;

  5. Has chronic daily use (more than 30 consecutive days during the last six months prior
     to enrollment) of opioid analgesia for any reason;

  6. Has a diagnosis of chronic pain or chronic pain syndrome (eg, chronic pain from the
     repeated vaso-occlusive events, chronic pain from avascular necrosis);

  7. Has a history of Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C
     infection;

  8. Has a history of documented episode(s) of priapism within 12 months of the Screening
     Visit;

  9. Has a history of atrial or ventricular arrhythmia;

 10. Has an international normalized ratio (INR) >2.0, or is on regular anticoagulation
     therapy, or has a history of a known bleeding diathesis;

 11. Has thrombocytopenia (platelets less than 80,000) or is on chronic acetylsalicylic
     acid therapy;

 12. Has increased risk of stroke: documented abnormal or "high conditional" transcranial
     Doppler (TCD) mean velocity (TCD V) by STOP criteria (Adams, 1998) within the
     preceding year or has a history of known cerebrovascular disease:

       -  "High conditional" = TCD V greater than or equal to 185 to 199 cm/sec, or TCDi V
  greater than or equal to 170 to 184 cm/sec, or TCD maximum V greater than or
  equal to 250 cm/sec; or

       -  Abnormal = TCD V greater than or equal to 200 cm/sec, or abnormal high TCDi V
  greater than or equal to 185 cm/sec, or TCD maximum V greater than or equal to
  250 cm/sec;

 13. Has received a blood transfusion or exchange transfusion in the two months prior to
     the Screening Visit or three months prior to randomization or has hemoglobin A (HbA)
     levels greater than 15% at the Screening Visit;

 14. Has renal insufficiency (creatinine greater than 1.5 times upper limit of normal
     [ULN], or requiring peritoneal dialysis or hemodialysis);

 15. Has liver dysfunction (ALT greater than 2.0 times ULN);

 16. Has other concomitant chronic medical or psychiatric condition that, in the opinion
     of the Investigator, would compromise participation in the study 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 patient participating in the
     study);

 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 during the course of the
     study;

 19. Has been treated with an experimental anti-sickling medication/treatment within 30
     days of the Screening Visit or during the course of the study;

 20. Is currently taking or has been treated with any investigational drug for any disease
     within 30 days of the Screening Visit or during the course of the study;

 21. Is currently enrolled in an investigational drug or device study and/or has
     participated in such a study within 30 days of the Screening Visit or during the
     course of the study; or

 22. There are factors that would, in the judgment of the Investigator, make it difficult
     for the patient to comply with the requirements of the study (eg, inability to
     swallow capsules due to past history of stroke, or poor compliance).

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