L-citrulline Injection in Patients Aged 6-21 Years Old with Sickle Cell Disease Presenting with Vaso-Occlusive Crisis (VOC)

Trial details

Who runs it

Asklepion Pharmaceuticals, LLC

Trial code

NCT04852172

Record updated

19 September 2024

Original description

The purpose of this study is to determine if intravenous L-citrulline can abrogate an active vaso-occlusive crisis in sickle cell disease, resulting in decreased pain, reduction or elimination of opiate usage, and reduction or elimination of hospital admission. The applicant is developing intravenous L-citrulline (Turnobi™) for treatment of sickle cell disease (SCD). The current development program targets treatment of sickle cell-associated vaso-occlusive crisis (VOC) specifically. The aim of Part 1 is to identify the optimum dose regimens for the Part 2 of the trial which is a double-blind, placebo controlled adaptive 'pick-the-winner' design. This study will allow assignment of more subjects to the better treatment arm/s based on emerging data. The study, initially, will evaluate efficacy and tolerability of incremental doses of intravenous (IV) L-citrulline (Turnobi™) in patients with SCD while receiving standard of care therapy for VOC.Read full original descriptionShow less

A Phase I/IIA Open-label Dose-Finding Study with Subsequent Double-blind, Placebo-controlled, Randomized Study of L-citrulline in Sickle Cell Disease Presenting to Emergency Department (ED) in Vaso Occlusive Crisis (VOC) in Children, Adolescents and Young Adults (6 to 21 Years)

The purpose of this study is to determine if intravenous L-citrulline can abrogate an active vaso-occlusive crisis in sickle cell disease, resulting in decreased pain, reduction or elimination of opiate usage, and reduction or elimination of hospital admission. The applicant is developing intravenous L-citrulline (Turnobi™) for treatment of sickle cell disease (SCD). The current development program targets treatment of sickle cell-associated vaso-occlusive crisis (VOC) specifically. The aim of Part 1 is to identify the optimum dose regimens for the Part 2 of the trial which is a double-blind, placebo controlled adaptive 'pick-the-winner' design. This study will allow assignment of more subjects to the better treatment arm/s based on emerging data. The study, initially, will evaluate efficacy and tolerability of incremental doses of intravenous (IV) L-citrulline (Turnobi™) in patients with SCD while receiving standard of care therapy for VOC.

Inclusion: Sickle cell disease (all genotypes); Children, adolescents and young adults between ages 6 to 21 years; In a steady disease state and not in the midst of any acute complication other than VOC due to sickle cell disease at study entry; For female of childbearing potential, a negative urine pregnancy test and using an adequate method of contraception, or denies sexual activity; Subjects or parents or legal guardian of the subject who are willing and able to sign and provide consent and assent (where appropriate for the age of the child).

Exclusion: >6 hospital admissions in the prior year; Systemic steroid therapy within the last 48 hours; Medications that are known to be contra-indicated with use of L-citrulline; Received any blood products within 3 weeks of the screening visit; History of opioid dependence/substance abuse; Has been on a clinical trial of a new therapy for sickle cell disease within the last 3 months; Presence of any other complication related to sickle cell disease such as splenic sequestration, hepatic sequestration, stroke, avascular necrosis of the hip/shoulder, acute priapism, renal dysfunction, dactylitis, acute chest syndrome and other major medical conditions or organ dysfunction; History of red blood cell transfusion within the last 30 days; Presence of acute chest syndrome, sepsis, bacterial infection, hemodynamic instability; History of allergic reaction to L-citrulline product; History of diabetes; Severe anemia (hemoglobin <6 g/dL); Serum creatinine levels:; Age 6 to 13 years >0.9 mg/dL; Age 14 to 17 years >1.0 mg/dL; Age >18 years >1.5 mg/dL; Subjects with a baseline prothrombin time International Normalized ratio (INR) >2.0; Subjects with inability to have parental assent given (ages 6 to 17 years) or consent (ages 18 through 21 years); Note: Parents or legal guardians can provide consent for subjects who are unable to provide assent (eg, sleepy or preoccupied by their pain); Current pain lasting >3 days; Pregnancy or lactation (subjects must have a negative urine pregnancy test); Report of fever (>38°C) within last 48 hours; Unreliable venous access; The PI considers that the subject will be unable to comply with the study requirements.

ClinicalTrials.gov NCT04852172