L-Citrulline for Sickle Cell Disease

Recruiting at 5 trial locations

Overseen By Gurdyal Kalsi, MD, MFPM (Hon)

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Asklepion Pharmaceuticals, LLC

Must not be taking: Steroids, Nitrates, Sildenafil, others

Disqualifiers: Sepsis, Stroke, Severe anemia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 1 day

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to learn more about a possible new treatment for pain episodes (called vaso-occlusive crises or VOCs) in children, teens, and young adults with sickle cell disease (SCD). The study will include about 120 participants between the ages of 6 and 21 who come to the emergency department (ED) with a VOC. A VOC is a painful episode that happens with no clear cause and no signs of infection or major problems with organs like the liver or kidneys. Before joining the study, patients and their families may be asked to learn about it and give permission (called consent or assent) while at a regular clinic visit. If that hasn't happened yet, the consent/assent process will happen at the emergency department when the patient comes in for care. If the patient meets all the study requirements, they can join the treatment part of the study. Participants will be randomly assigned (like flipping a coin) to receive either: L-citrulline, the study drug, or A placebo, which looks the same but has no active ingredients. Everyone has an equal chance of getting either one. The study drug is given through an IV. It starts with one larger dose, followed by a steady infusion for up to 12 hours. All patients in the study will still receive the usual pain treatment (called standard of care), which may include opioids. However, some patients may need fewer opioids if the study treatment helps with their pain. If any medicines are not allowed during the study, the doctor will explain this during the consent process. Patients can go home once: Their pain is controlled with oral (by mouth) pain medicine, They're eating and drinking well, and They've been given a personal pain management plan to use at home. After leaving the hospital, the study team will follow up with patients by phone about 2 days later (within a 12-hour window), again around Day 7, and again around Day 30 to check how they're doing.

Research Team

Suvankar Majumdar, MD

Principal Investigator

Center for Cancer and Blood Disorders, Children's National Hospital

Eligibility Criteria

This trial is for children and young adults aged 6-21 with Sickle Cell Disease experiencing a pain episode known as vaso-occlusive crisis. They must be able to give consent or have a guardian who can, and should not be taking any medications that are disallowed in the study.

Inclusion Criteria

Patients or parents or legal guardian of the patient who are willing and able to sign and provide consent and assent (where appropriate for the age of the child)

I am between 6 and 21 years old.

My condition is stable and I have no acute issues except for pain crises due to sickle cell.

Exclusion Criteria

I haven't used medications like nitrates or sildenafil in the last 30 days.

I am unable to give consent due to my age.

History of allergic reaction to L-citrulline product or dextrose

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive either L-citrulline or placebo intravenously, with a bolus dose followed by a continuous infusion for up to 12 hours

1 day

In-patient hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up calls around Day 2, Day 7, and Day 30

30 days

3 follow-up calls

Treatment Details

Interventions

• L-citrulline

Trial Overview The trial tests if L-citrulline, an IV-administered drug, can reduce pain during sickle cell crises compared to a placebo. Participants will also receive standard pain treatments and are randomly assigned to either the drug or placebo group.

Participant Groups

Group I: L-citrulline Intravenous Treatment Arm Experimental Treatment 1 Intervention

Participants randomized to this arm will receive intravenous (IV) L-citrulline, a naturally occurring amino acid being investigated for its potential to treat vaso-occlusive crises (VOCs) in sickle cell disease. The study drug will be administered as a 50 mg/kg IV bolus, followed by a continuous infusion at 9 mg/kg/hour for up to 12 hours. The investigational product is provided as an isotonic solution in vials containing L-citrulline 50 mg/mL. Treatment will begin within 120 minutes of informed consent/assent and following the initial dose of opioid or ketamine, but prior to any subsequent doses. All participants will continue to receive standard-of-care (SoC) pain management per site protocol, which may be adjusted based on clinical response to study treatment.

Group II: Placebo Placebo Group 1 Intervention

Participants randomized to this arm will receive a placebo intravenous (IV) treatment designed to match the appearance and administration schedule of L-citrulline. The placebo will be given as a single bolus dose followed by a continuous infusion for up to 12 hours. All participants will continue to receive standard of care pain management for sickle cell disease, consistent with the treating site's protocol and adjusted as needed based on the patient's clinical condition.

Who Is Running the Clinical Trial?

Asklepion Pharmaceuticals, LLC

Lead Sponsor

Trials

6

Recruited

450+