Acute Vaso Occlusive Crisis (VOC)Phase 1/2NCT04852172
L-citrulline Injection in Patients Aged 6-21 Years Old with Sickle Cell Disease Presenting with Vaso-Occlusive Crisis (VOC)
A Phase 1/2 study testing L-citrulline and D5 1/2NS in people with Acute Vaso Occlusive Crisis (VOC), run by Asklepion Pharmaceuticals, LLC at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 21 years
- Conditions the study is for
- Acute Vaso Occlusive Crisis (VOC)
- What is being tested?
- L-citrulline and D5 1/2NS
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- 29 Apr 2021to 29 Feb 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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).
Who cannot join
- 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)
Show all 24Show fewer
- 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
- 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).
- History of allergic reaction to L-citrulline product
- Medications that are known to be contra-indicated with use of L-citrulline
- History of diabetes.
- Subjects with a baseline prothrombin time International Normalized ratio (INR) >2.0.
- Received any blood products within 3 weeks of the screening visit.
- Unreliable venous access
- The PI considers that the subject will be unable to comply with the study requirements.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The University of Mississippi Medical Center
Jackson, Mississippi, 39216
Children's National Hospital
Washington D.C., District of Columbia, 20010
About this study
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)
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 the detailed description
Overall Design:
This is a study in children, adolescents, and young adults (6 to 21 years) with SCD presenting to an emergency department (ED) with VOC. Children below age 6 are likely to be recruited in a subsequent phase, once proof of concept is established on optimized dose regimen. Eligible subjects will have documented SCD. Intravenous L citrulline (Turnobi™) or placebo will be administered in addition to standard of care VOC therapy to children, adolescents, and young adults presenting with SCD VOC - defined as painful episode without other apparent causes of pain and without significant organ dysfunction or signs of systemic infection.
This is a single center study, conducted in 2 parts:
Part 1: This is an open-label, ascending dose part of the study. After obtaining the informed consent/assent, the enrolled subjects will be in the ED for up to 7 hours where L-citrulline will be administered as depicted in the dosing panel below. Each dose will be administered sequentially until 5 subjects per dose cohort are accrued.
Dosing panels in Part 1:
25 mg/kg bolus + 9 mg/kg/hr infusion; 50 mg/kg bolus + 9 mg/kg/hr infusion; 100 mg/kg bolus + 9 mg/kg/hr infusion; 100 mg/kg bolus + 11 mg/kg/hr infusion;
After each panel of 5 have been dosed, response to a dose is determined by the Principal Investigator (PI) with the internal review committee based primarily on analgesic effects assessed by review of Visual Analogue Scale (VAS) score, opioid dosing, and tolerability.
If the dose panel is assessed safe and 3 of 5 subjects in a cohort respond to the treatment, the current dose arm will continue to accrue a total of 10 subjects. If the dose panel is assessed as safe; however, fewer than 3 of the 5 subjects respond, the current dose arm will be stopped, and the subjects will be recruited to the next dosing panel.
Two additional panels of 5 to 10 subjects receiving doses outside these ranges may be accrued at the request of the internal review committee if determined necessary to achieve the study's objectives. As long as supported by emerging data, the subjects in these additional panels may receive a lower or higher bolus injection but no greater than 150 mg/kg bolus and/or a lower or higher infusion dose but no greater than 15 mg/kg/hour. Up to 60 subjects may be enrolled in Part 1 of the study with a likely sample size of approximately 40 subjects.
Part 1 of the study is intended to select up to 2 effective and tolerated dose regimens for Part 2 of the study.
Part 2: The optimal dose regimens (at least1 but probably 2) selected from Part 1 will be analyzed in a randomized, double-blind, placebo-controlled adaptive pick-the-winner design. This will allow assignment of more subjects to the better treatment arm/s based on emerging data. Efficacy will be based primarily on analgesic effect assessed by VAS/opioid dose composite, admission or not, and tolerability based on adverse drug reactions by the internal review committee.
A total of 60 subjects will take part in Part 2. Subjects will be randomized to 2 of the doses selected from Part 1 and placebo in a 1:1:1 ratio. After 30 subjects (10 per treatment arm) have been randomized, an interim analysis will be performed. If the higher dose is providing markedly more pain relief than the lower dose - with no safety issues - then the lower dose will be dropped. Otherwise, if efficacy and safety look similar, the lower dose will be retained, and the higher dose will be dropped. In other words, the most successful active treatment arm will be chosen for further study versus placebo. The internal review committee will be responsible for making this decision. Subsequently, 30 more patients will be randomized in a 1:1 fashion in the remaining 2 study arms (15 patients each). In the unlikely case that the placebo arm demonstrates superior response to both active treatment arms, the interval review committee will recommend discontinuing the study.
If after 30 subjects, it is determined by the internal review committee that 1 of the 2 doses is significantly more effective in subjects with particular characteristics, the less effective L-citrulline dose regimen can be dropped for those subjects, eg, if those with more severe VOC only respond to the higher dose but those with less severe VOC respond equally well to either dose, subjects with severe VOC will be adaptively allocated into a separate stratum and randomized only to the higher dose or placebo.
All subjects in both Part 1 and Part 2 will receive standard of care for analgesia per SCD pain management protocol consistent with the Children's national ED guidance guided individualized care plan irrespective of treatment with study treatment or placebo. The end of the study is defined as the date of the last visit of the last subject in the study or last scheduled procedure the last subject in the study.
- Conditions
- Acute Vaso Occlusive Crisis (VOC)
- Being tested
- L-citrulline, D5 1/2NS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-citrullineDrug
Also called L-CIT, CIT
L-citrulline is a naturally occurring amino acid. It is produced by, and normally present in, the human body.
D5 1/2NSOther
Also called Saline
Saline
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (L-citrulline) | Active comparator | 25 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours Receives: 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 Receives: 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 Receives: 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 Receives: 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. Receives: 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. Receives: Other: D5 1/2NS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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
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
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
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
Measured: 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.
Measured: 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
Measured: 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
Measured: Collected from enrollment to end of study over 18 months
Secondary outcomes (4)
Preliminary assessment of pain change measured
The standard of care Visual Analog Scale (VAS) pain scale will be administered at baseline then every 15 minutes after the start of study
Measured: Collected from enrollment to end of study (2-Days)
Preliminary assessment of change of opioid use overall
The standard of care will be followed for pain management. the amount of opioids consumed will be collected.
Measured: Collected from enrollment to end of study (30 Days)
Time to clinical resolution of VOC
Time to clinical resolution of VOC depicted by sustained VAS score; assessed every 15 minutes
Measured: Collected from enrollment to end of study (30 Days)
Duration or length of hospital stay
Data collected from the ED visit through day 30 follow-up will look at reoccurrence of admission.
Measured: Collected from enrollment to end of study (30-Days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2021
- Study start29 Apr 2021
- Primary completion29 Feb 2024
- Study completion29 Feb 2024
Why it stopped: Impacted by viraemia resulting in higher than expected admissions
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Vaso Occlusive Crisis (VOC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asklepion Pharmaceuticals, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gurdyal Kalsi, MD, MFPM, Study director, Asklepion Pharmaceuticals, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04852172
- Sponsor's protocol ID
- CIT-SCD-001-01
- Status last verified
- Aug 2023
- First submitted
- 18 Mar 2021
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04852172
- Acronym / sponsor ID
- CIT-SCD-001-01
- Conditions
- Acute Vaso Occlusive Crisis (VOC)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Impacted by viraemia resulting in higher than expected admissions
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Asklepion Pharmaceuticals, LLCIndustry (pharma, biotech, devices)
- Study start
- 29 Apr 2021 (actual)
- Primary completion
- 29 Feb 2024 (actual)
- Study completion
- 29 Feb 2024 (actual)
- First posted
- 21 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Overall Design:
This is a study in children, adolescents, and young adults (6 to 21 years) with SCD presenting to an emergency department (ED) with VOC. Children below age 6 are likely to be recruited in a subsequent phase, once proof of concept is established on optimized dose regimen. Eligible subjects will have documented SCD. Intravenous L citrulline (Turnobi™) or placebo will be administered in addition to standard of care VOC therapy to children, adolescents, and young adults presenting with SCD VOC - defined as painful episode without other apparent causes of pain and without significant organ dysfunction or signs of systemic infection.
This is a single center study, conducted in 2 parts:
Part 1: This is an open-label, ascending dose part of the study. After obtaining the informed consent/assent, the enrolled subjects will be in the ED for up to 7 hours where L-citrulline will be administered as depicted in the dosing panel below. Each dose will be administered sequentially until 5 subjects per dose cohort are accrued.
Dosing panels in Part 1:
25 mg/kg bolus + 9 mg/kg/hr infusion; 50 mg/kg bolus + 9 mg/kg/hr infusion; 100 mg/kg bolus + 9 mg/kg/hr infusion; 100 mg/kg bolus + 11 mg/kg/hr infusion;
After each panel of 5 have been dosed, response to a dose is determined by the Principal Investigator (PI) with the internal review committee based primarily on analgesic effects assessed by review of Visual Analogue Scale (VAS) score, opioid dosing, and tolerability.
If the dose panel is assessed safe and 3 of 5 subjects in a cohort respond to the treatment, the current dose arm will continue to accrue a total of 10 subjects. If the dose panel is assessed as safe; however, fewer than 3 of the 5 subjects respond, the current dose arm will be stopped, and the subjects will be recruited to the next dosing panel.
Two additional panels of 5 to 10 subjects receiving doses outside these ranges may be accrued at the request of the internal review committee if determined necessary to achieve the study's objectives. As long as supported by emerging data, the subjects in these additional panels may receive a lower or higher bolus injection but no greater than 150 mg/kg bolus and/or a lower or higher infusion dose but no greater than 15 mg/kg/hour. Up to 60 subjects may be enrolled in Part 1 of the study with a likely sample size of approximately 40 subjects.
Part 1 of the study is intended to select up to 2 effective and tolerated dose regimens for Part 2 of the study.
Part 2: The optimal dose regimens (at least1 but probably 2) selected from Part 1 will be analyzed in a randomized, double-blind, placebo-controlled adaptive pick-the-winner design. This will allow assignment of more subjects to the better treatment arm/s based on emerging data. Efficacy will be based primarily on analgesic effect assessed by VAS/opioid dose composite, admission or not, and tolerability based on adverse drug reactions by the internal review committee.
A total of 60 subjects will take part in Part 2. Subjects will be randomized to 2 of the doses selected from Part 1 and placebo in a 1:1:1 ratio. After 30 subjects (10 per treatment arm) have been randomized, an interim analysis will be performed. If the higher dose is providing markedly more pain relief than the lower dose - with no safety issues - then the lower dose will be dropped. Otherwise, if efficacy and safety look similar, the lower dose will be retained, and the higher dose will be dropped. In other words, the most successful active treatment arm will be chosen for further study versus placebo. The internal review committee will be responsible for making this decision. Subsequently, 30 more patients will be randomized in a 1:1 fashion in the remaining 2 study arms (15 patients each). In the unlikely case that the placebo arm demonstrates superior response to both active treatment arms, the interval review committee will recommend discontinuing the study.
If after 30 subjects, it is determined by the internal review committee that 1 of the 2 doses is significantly more effective in subjects with particular characteristics, the less effective L-citrulline dose regimen can be dropped for those subjects, eg, if those with more severe VOC only respond to the higher dose but those with less severe VOC respond equally well to either dose, subjects with severe VOC will be adaptively allocated into a separate stratum and randomized only to the higher dose or placebo.
All subjects in both Part 1 and Part 2 will receive standard of care for analgesia per SCD pain management protocol consistent with the Children's national ED guidance guided individualized care plan irrespective of treatment with study treatment or placebo. The end of the study is defined as the date of the last visit of the last subject in the study or last scheduled procedure the last subject in the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
- 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).
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (L-citrulline) | Active comparator | Drug: L-citrulline25 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours |
| Arm 2 (L-citrulline) | Active comparator | Drug: L-citrulline50 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours |
| Arm 3 (L-citrulline) | Active comparator | Drug: L-citrulline100 mg/kg bolus + 9 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours |
| Arm 4 (L-citrulline) | Active comparator | Drug: L-citrulline100 mg/kg bolus + 11 mg/kg/hr continuous infusion of L-citrulline for up to 7 hours |
| Part 2 Arm 1 (L-citrulline) | Active comparator | Drug: L-citrullineSubjects 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. |
| Part 2 Arm 2 D5 1/2NS | Placebo comparator | Other: D5 1/2NSSubjects will be randomized to 2 of the doses selected from Part 1 and placebo in a 1:1:1 ratio. |
Who may qualify
- Ages
- 6 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-citrullineAlso: L-CIT, CITL-citrulline is a naturally occurring amino acid. It is produced by, and normally present in, the human body. | Drug | Arm 1 (L-citrulline), Arm 2 (L-citrulline), Arm 3 (L-citrulline), Arm 4 (L-citrulline), Part 2 Arm 1 (L-citrulline) |
| D5 1/2NSAlso: SalineSaline | Other | Part 2 Arm 2 D5 1/2NS |
Primary outcome
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.
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
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
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
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
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
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.
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
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
4 secondary outcomes
Preliminary assessment of pain change measured
Time frame: Collected from enrollment to end of study (2-Days)
Preliminary assessment of change of opioid use overall
Time frame: Collected from enrollment to end of study (30 Days)
Time to clinical resolution of VOC
Time frame: Collected from enrollment to end of study (30 Days)
Duration or length of hospital stay
Time frame: Collected from enrollment to end of study (30-Days)
Results and safety
The study was stopped early (reason given: Impacted by viraemia resulting in higher than expected admissions). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gurdyal Kalsi, MD, MFPM study director
Asklepion Pharmaceuticals, LLC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing L-citrulline and D5 1/2NS in people with Acute Vaso Occlusive Crisis (VOC), run by Asklepion Pharmaceuticals, LLC at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Impacted by viraemia resulting in higher than expected admissions). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Optimization (Part 1) (time frame: Collected from enrollment to end of study over 18 months). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.