We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04852172
Recruitment Status : Recruiting
First Posted : April 21, 2021
Last Update Posted : January 30, 2023
Sponsor:
Information provided by (Responsible Party):
Asklepion Pharmaceuticals, LLC

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.

Condition or disease Intervention/treatment Phase
Acute Vaso Occlusive Crisis (VOC) Drug: L-citrulline Other: D5 1/2NS Phase 1 Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blind placebo controlled (Part 2)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : April 29, 2021
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : July 1, 2023


Arm Intervention/treatment
Active Comparator: Arm 1 (L-citrulline)
25 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours
Drug: L-citrulline
L-citrulline is a naturally occurring amino acid. It is produced by, and normally present in, the human body.
Other Name: L-CIT, CIT

Active Comparator: Arm 2 (L-citrulline)
50 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours
Drug: L-citrulline
L-citrulline is a naturally occurring amino acid. It is produced by, and normally present in, the human body.
Other Name: L-CIT, CIT

Active Comparator: Arm 3 (L-citrulline)
100 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours
Drug: L-citrulline
L-citrulline is a naturally occurring amino acid. It is produced by, and normally present in, the human body.
Other Name: L-CIT, CIT

Active Comparator: Arm 4 (L-citrulline)
100 mg/kg bolus + 11 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours
Drug: L-citrulline
L-citrulline is a naturally occurring amino acid. It is produced by, and normally present in, the human body.
Other Name: L-CIT, CIT

Active Comparator: Part 2 Arm 1 (L-citrulline)
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
L-citrulline is a naturally occurring amino acid. It is produced by, and normally present in, the human body.
Other Name: L-CIT, CIT

Placebo Comparator: Part 2 Arm 2 D5 1/2NS
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
Saline
Other Name: Saline




Primary Outcome Measures :
  1. Dose Optimization (Part 1) [ Time Frame: Collected from enrollment to end of study over 18 months ]
    During Part 1 of the study four cohorts will be enrolled. Cohorts will be squentially completed. Each cohort has a different dosing schema.

  2. To determine the how the study medication is processed by the body. [ Time Frame: Collected from enrollment to Emergency room Discharge, Approximability 7 Hours ]
    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

  3. To determine the how the study medication is processed by the body. [ Time Frame: Collected from enrollment to Emergency room Discharge, Approximability 7 Hours ]
    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

  4. To determine the how the study medication is processed by the body. [ Time Frame: Collected from enrollment to Emergency room Discharge, Approximability 7 Hours ]
    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

  5. To determine the how the study medication is processed by the body. [ Time Frame: Collected from enrollment to Emergency room Discharge, Approximability 7 Hours ]
    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

  6. Change in Visual Analogue Scale (VAS) pain score [ Time Frame: Collected from enrollment to end of study over 18 months ]
    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

  7. Change from baseline in amount of overall opioid use [ Time Frame: Collected from enrollment to end of study over 18 months ]
    Opioid consumption will be recorded from baseline to end of study.

  8. Discharge from ED/hospital within 7 hours [ Time Frame: Collected from enrollment to end of study over 18 months ]
    Time spent in the ED/hospital will be collected

  9. Assessment of safety [ Time Frame: Collected from enrollment to end of study over 18 months ]
    The rate of reported AE analysis and Lab abnormalities for each cohort


Secondary Outcome Measures :
  1. Preliminary assessment of pain change measured [ Time Frame: Collected from enrollment to end of study (2-Days) ]
    The standard of care Visual Analog Scale (VAS) pain scale will be administered at baseline then every 15 minutes after the start of study

  2. Preliminary assessment of change of opioid use overall [ Time Frame: Collected from enrollment to end of study (30 Days) ]
    The standard of care will be followed for pain management. the amount of opioids consumed will be collected.

  3. Time to clinical resolution of VOC [ Time Frame: Collected from enrollment to end of study (30 Days) ]
    Time to clinical resolution of VOC depicted by sustained VAS score; assessed every 15 minutes

  4. Duration or length of hospital stay [ Time Frame: Collected from enrollment to end of study (30-Days) ]
    Data collected from the ED visit through day 30 follow-up will look at reoccurrence of admission.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Sickle cell disease (all genotypes)
  2. Children, adolescents and young adults between ages 6 to 21 years
  3. 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
  4. For female of childbearing potential, a negative urine pregnancy test and using an adequate method of contraception, or denies sexual activity
  5. 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 Criteria:

  1. Current pain lasting >3 days
  2. >6 hospital admissions in the prior year
  3. History of opioid dependence/substance abuse
  4. Has been on a clinical trial of a new therapy for sickle cell disease within the last 3 months
  5. 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
  6. Severe anemia (hemoglobin <6 g/dL)
  7. History of red blood cell transfusion within the last 30 days
  8. Systemic steroid therapy within the last 48 hours
  9. Pregnancy or lactation (subjects must have a negative urine pregnancy test)
  10. Serum creatinine levels:

    1. Age 6 to 13 years >0.9 mg/dL
    2. Age 14 to 17 years >1.0 mg/dL
    3. Age >18 years >1.5 mg/dL
  11. Report of fever (>38°C) within last 48 hours
  12. Presence of acute chest syndrome, sepsis, bacterial infection, hemodynamic instability
  13. 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).

  14. History of allergic reaction to L-citrulline product
  15. Medications that are known to be contra-indicated with use of L-citrulline
  16. History of diabetes.
  17. Subjects with a baseline prothrombin time International Normalized ratio (INR) >2.0.
  18. Received any blood products within 3 weeks of the screening visit.
  19. Unreliable venous access
  20. The PI considers that the subject will be unable to comply with the study requirements.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04852172


Contacts
Layout table for location contacts
Contact: Gurdyal Kalsi, MD, MFPM 410-736-3750 gurdyal.kalsi@asklepionpharm.com
Contact: Heather Hill +1 433.839.5726 heather.hill@asklepionpharm.com

Locations
Layout table for location information
United States, District of Columbia
Children's National Hospital Recruiting
Washington, District of Columbia, United States, 20010
Contact: Suvankar Majumdar, MD       smajumdar@childrensnational.org   
Contact: Kara Hom       khom@childrensnational.org   
United States, Mississippi
The University of Mississippi Medical Center Recruiting
Jackson, Mississippi, United States, 39216
Contact: Matthew W Maready, MD, FAAP, FACEP    6019842195    mmaready@umc.edu   
Contact: Stephanie Moore, BSN,RN, NRP    6014967812    smoore13@umc.edu   
Sponsors and Collaborators
Asklepion Pharmaceuticals, LLC
Investigators
Layout table for investigator information
Study Director: Gurdyal Kalsi, MD, MFPM Asklepion Pharmaceuticals, LLC
Layout table for additonal information
Responsible Party: Asklepion Pharmaceuticals, LLC
ClinicalTrials.gov Identifier: NCT04852172    
Other Study ID Numbers: CIT-SCD-001-01
First Posted: April 21, 2021    Key Record Dates
Last Update Posted: January 30, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn