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

NCT04852172 | Terminated Phase 1 FDA Drug

• 1 other identifier: CIT-SCD-001-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Acute Vaso Occlusive Crisis (VOC)

Outcome Measures

Primary Outcomes (9)

• Dose Optimization (Part 1)

  During Part 1 of the study four cohorts will be enrolled. Cohorts will be squentially completed. Each cohort has a different dosing schema.

  Collected from enrollment to end of study over 18 months

• To determine the how the study medication is processed by the body.

  About 5 milliliters of blood will be collected before study medication is administered and then every 15 minutes to measure how much study drug is in your blood stream. The blood sample collected will be analyzed for Pharmacokinetic parameters Peak of drug in the blood will be measured

  Collected from enrollment to Emergency room Discharge, Approximability 7 Hours

• To determine the how the study medication is processed by the body.

  About 5 milliliters of blood will be collected before study medication is administered and then every 15 minutes to measure how much study drug is in your blood stream. The blood sample collected will be analyzed for Pharmacokinetic parameters Trough of drug in the blood will be measured

  Collected from enrollment to Emergency room Discharge, Approximability 7 Hours

• To determine the how the study medication is processed by the body.

  About 5 milliliters of blood will be collected before study medication is administered and then every 15 minutes to measure how much study drug is in your blood stream. The blood sample collected will be analyzed for Pharmacokinetic parameters of steady state concentration (Cmax) of drug in the blood will be measured

  Collected from enrollment to Emergency room Discharge, Approximability 7 Hours

• To determine the how the study medication is processed by the body.

  About 5 milliliters of blood will be collected before study medication is administered and then every 15 minutes to measure how much study drug is in your blood stream. The blood sample collected will be analyzed for Pharmacokinetic parameters of AUC of drug in the blood will be measured

  Collected from enrollment to Emergency room Discharge, Approximability 7 Hours

• Change in Visual Analogue Scale (VAS) pain score

  Please note that scale info should be entered in the outcome measure description field: at least 2-point decrease or 30% change in pain intensity VAS or Faces Pain Scale score RANGE from 0 (No pain) to 100 (Maximum Pain) (for subjects 6 to 7 years old) when compared with baseline value; assessed every 15 minutes

  Collected from enrollment to end of study over 18 months

• Change from baseline in amount of overall opioid use

  Opioid consumption will be recorded from baseline to end of study.

  Collected from enrollment to end of study over 18 months

• Discharge from ED/hospital within 7 hours

  Time spent in the ED/hospital will be collected

  Collected from enrollment to end of study over 18 months

• Assessment of safety

  The rate of reported AE analysis and Lab abnormalities for each cohort

  Collected from enrollment to end of study over 18 months

Secondary Outcomes (4)

• Preliminary assessment of pain change measured

  Collected from enrollment to end of study (2-Days)

• Preliminary assessment of change of opioid use overall

  Collected from enrollment to end of study (30 Days)

• Time to clinical resolution of VOC

  Collected from enrollment to end of study (30 Days)

• Duration or length of hospital stay

  Collected from enrollment to end of study (30-Days)

Study Arms (6)

Arm 1 (L-citrulline)

ACTIVE COMPARATOR

25 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours

Drug: L-citrulline

Arm 2 (L-citrulline)

ACTIVE COMPARATOR

50 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours

Drug: L-citrulline

Arm 3 (L-citrulline)

ACTIVE COMPARATOR

100 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours

Drug: L-citrulline

Arm 4 (L-citrulline)

ACTIVE COMPARATOR

100 mg/kg bolus + 11 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours

Drug: L-citrulline

Part 2 Arm 1 (L-citrulline)

ACTIVE COMPARATOR

Subjects will be randomized to 2 of the doses selected from Part 1 and placebo in a 1:1:1 ratio. L-citrulline will be administered to the active arm.

Drug: L-citrulline

Part 2 Arm 2 D5 1/2NS

PLACEBO COMPARATOR

Subjects will be randomized to 2 of the doses selected from Part 1 and placebo in a 1:1:1 ratio.

Other: D5 1/2NS

Interventions

L-citrulline DRUG

L-citrulline is a naturally occurring amino acid. It is produced by, and normally present in, the human body.

Also known as: L-CIT, CIT

Arm 1 (L-citrulline); Arm 2 (L-citrulline); Arm 3 (L-citrulline); Arm 4 (L-citrulline); Part 2 Arm 1 (L-citrulline)

D5 1/2NS OTHER

Saline

Also known as: Saline

Part 2 Arm 2 D5 1/2NS

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• Current pain lasting \>3 days
• \>6 hospital admissions in the prior year
• 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
• Severe anemia (hemoglobin \<6 g/dL)
• History of red blood cell transfusion within the last 30 days
• Systemic steroid therapy within the last 48 hours
• Pregnancy or lactation (subjects must have a negative urine pregnancy test)
• 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
• Report of fever (\>38°C) within last 48 hours
• Presence of acute chest syndrome, sepsis, bacterial infection, hemodynamic instability

Sponsors & Collaborators

• Asklepion Pharmaceuticals, LLC: lead

Study Sites (2)

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

The University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

MeSH Terms

Interventions

Citrulline; serum P-component; Sodium Chloride

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Gurdyal Kalsi, MD, MFPM

  Asklepion Pharmaceuticals, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind placebo controlled (Part 2)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: April 21, 2021
• Study Start: April 29, 2021
• Primary Completion: February 29, 2024
• Study Completion: February 29, 2024
• Last Updated: September 19, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)