Intracerebral HemorrhagePhase 2S-CATCHNCT03711903
Evaluation of CN-105 in Subject With Acute Supratentorial Intracerebral Hemorrhage
A Phase 2 study testing Acetyl-Valine-Serine-Arginine-Arginine-Arginine-NH2 (Ac-VSRRR- NH2). and 0.9% Sodium-chloride in people with Intracerebral Hemorrhage, run by National Neuroscience Institute at 1 site in Singapore.
Trial summary
Phase 2, randomized, double-blind, placebo controlled study to evaluate the administration of CN-105 in patients with supratentorial intracerebral hemorrhage (ICH). Patients will be evaluated for eligibility within 12 hours of symptom onset. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Intracerebral Hemorrhage
- What is being tested?
- Acetyl-Valine-Serine-Arginine-Arginine-Arginine-NH2 (Ac-VSRRR- NH2). and 0.9% Sodium-chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteSingapore
- Study dates
- 24 Mar 2019to 16 Jun 2022
- Phase
- Phase 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 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has given written informed consent to participate in the study in accordance with required regulations; if a participant is not capable of providing informed consent, written consent must be obtained from the participant's legally authorized representative (LAR).
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Is male or female, age 30 to 80 years, inclusive.
- Has a confirmed diagnosis of spontaneous supratentorial ICH.
- Able to receive first dose of study drug ≤ 12 hours after onset of ICH symptoms, such as alteration in level of consciousness, severe headache, nausea, vomiting, seizure, and/or focal neurological deficits, or last-known well time.
- Has an interpretable and measurable diagnostic CT scan.
Show all 9Show fewer
- Has a GCS score ≥ 5 on presentation
- Has a National Institutes of Health Stroke Scale (NIHSS) score ≥ 4
- Has systolic BP (SBP) < 200 mm Hg at enrollment.
Who cannot join
- 1Known pregnancy and lactation 2.Has a temperature greater than 38.5°C at Screening. 3.ICH known to result from trauma. 4.Evidence of infratentorial hemorrhage (any involvement of the midbrain or lower brainstem as demonstrated by radiograph or complete third nerve palsy) severely limiting the recovery potential of the patient in the opinion of the investigator.
- 5.Evidence of primary intraventricular hemorrhage deemed to be at high risk for obstructive hydrocephalus, in the opinion of the investigator or evidence of extra-axial (i.e., subarachnoid or subdural) extension of hemorrhage severely limiting the recovery potential of the patient in the opinion of the investigator.
- 6.Radiographic evidence of underlying tumor. 7.Known unstable mass or active radiographic evidence and symptoms of herniation syndromes severely limiting the recovery potential of the patient in the opinion of the investigator.
- 8.Known ruptured aneurysm, arteriovenous malformation, or vascular anomaly. 9.Has a platelet count < 100,000/mL. 10.Has an international normalized ratio (INR) > 1.5 or irreversible coagulopathy either due to medical condition or detected before screening.
- 11.Is taking new oral anticoagulants (NOACS) or low molecular weight heparin at the time of ICH onset 12.In the opinion of the investigator is unstable and would benefit from supportive care rather than supportive care plus CN-105.
- 13. In the opinion of the investigator has any contraindication to the planned study assessments, including CT and MRI.
- 14.Any condition which could interfere with, or the treatment for which might interfere with, the conduct of the study or which, in the opinion of the investigator, unacceptably increases the individual's risk by participating in the study.
- 15.Concomitant enrollment in another interventional study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2, Randomized, Double Blind, Placebo , Controlled Study To Evaluate The Administration of CN-105 In Participants With Acute Supratentorial Intracerebral Hemorrhage
Phase 2, randomized, double-blind, placebo controlled study to evaluate the administration of CN-105 in patients with supratentorial intracerebral hemorrhage (ICH). Patients will be evaluated for eligibility within 12 hours of symptom onset. Eligible participants (30 active participants and 30 control participants) will receive CN-105 or placebo administered intravenously (IV) for a 30-minute infusion every 6 hours for up to a maximum of 3 days (13 doses) or until discharge (if earlier than 3 days). Participants will be monitored daily throughout the Treatment phase of the study (up to a maximum of 5 days) and will receive standard-of-care treatment for the duration of the study. Additional protocol assessments will be required during the Treatment phase as outlined in Section 7.5. After discharge from the hospital, participants will enter a 3-month Follow-up phase, with a clinic visit at 30 days and a follow-up telephone interview with telephone-validated mRS at 90 days after first dose of study agent.
Read the detailed description
Phase 2, randomized, double-blind, placebo controlled study to evaluate the administration of CN-105 in patients with supratentorial intracerebral hemorrhage (ICH). Patients will be evaluated for eligibility within 12 hours of symptom onset. Eligible participants (30 active participants and 30 control participants) will receive CN-105 or placebo administered intravenously (IV) for a 30-minute infusion every 6 hours for up to a maximum of 3 days (13 doses) or until discharge (if earlier than 3 days). Participants will be monitored daily throughout the Treatment phase of the study (up to a maximum of 5 days) and will receive standard-of-care treatment for the duration of the study. Additional protocol assessments will be required during the Treatment phase as outlined in Section 7.5. After discharge from the hospital, participants will enter a 3-month Follow-up phase, with a clinic visit at 30 days and a follow-up telephone interview with telephone-validated mRS at 90 days after first dose of study agent.
The study is not powered to test any specific hypothesis in regard to safety and will instead use descriptive methods to describe the experience of the study cohort with respect to adverse and serious adverse events (SAEs), as well as the occurrence of several pre-specified events of interest. The secondary objective of this study will be met by comparing the modified Rankin score (mRS) at 30 days between participants treated with CN-105 with placebo controlled participants The mRS at 30 days will be compared between treated and control participants using the Wilcoxon rank sum test. Exploratory analyses include comparison of treated and control participants for radiographic cerebral edema and hematoma volume and expansion and biological markers of inflammation.
Primary: To assess safety of CN-105 administration in primary ICH.
Secondary: To evaluate whether the administration of CN-105 improves 30-day mortality and functional outcomes by comparing participants treated with CN-105 with placebo controlled participants.
Exploratory:
- To investigate feasibility of Day 0, 1, 2, and 5 non-contrast head computed tomography (CT) as a radiographic surrogate to evaluate progression of perihematomal edema
- To investigate feasibility of using serial biochemical markers of neuroinflammation and neuronal injury as a surrogate measure of perihematomal edema and clinical outcome in the setting of spontaneous ICH.Primary:
- Number and severity of AEs throughout the duration of the study
- Number and severity of SAEs throughout the duration of the study
- In-hospital, 30-day, and 90-day mortality
- Treatment-related mortality
- In-hospital neurological deterioration, defined as an increase of National Institutes of Health Stroke Scale (NIHSS), > 2 from baseline and/or decrease of > 2 of Glasgow Coma Scale (GCS), persisting more than 24 hours, and unrelated to sedation
- Incidence of cerebritis, meningitis, ventriculitis
- Incidence of systemic infection
- Incidence of hematoma extension Secondary:.
- 30- and 90-day mRS
- Need for intracranial hypertension management
- NIHSS score, Glasgow Coma Scale, Montreal Cognitive Assessment, Stroke Impact Scale-16, and Barthel Index assessment at hospital discharge and 30 days after ICH
- Discharge disposition
Exploratory:
- Day 0, 1, 2, 5 non-contrast head CT as a radiographic surrogate to evaluate progression of perihematomal edema
- Biochemical surrogates of brain injury, including plasma concentrations of S100B, glial fibrillary acidic protein, metalloproteinase-3 and -9, C-reactive protein, D-dimer, brain natriuretic peptide, interleukin-6, tumor necrosis factor-α, and vascular endothelial growth factor, assessed daily for 5 days after ICH or until discharge (concentration time area under the curve assessed for each biomarker)
- Conditions
- Intracerebral Hemorrhage
- Being tested
- Acetyl-Valine-Serine-Arginine-Arginine-Arginine-NH2 (Ac-VSRRR- NH2)., 0.9% Sodium-chloride
- Medical subject headings
- Cerebral Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetyl-Valine-Serine-Arginine-Arginine-Arginine-NH2 (Ac-VSRRR- NH2).Drug
Also called CN105
The study drug, CN-105 is supplied in amber glass vials containing 4 mL of a concentrated 12.5-mg/mL clear-to-slightly-yellow solution.
0.9% Sodium-chlorideDrug
normal saline
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | The study drug, CN-105, will be administered at 1.0 mg/kg every 6 +/- 1 hour. The calculated volumes of study agent will be removed from the vials and transferred to 250 mL of normal saline (0.9% sodium chloride injection, USP). The recorded weight at baseline will be used to determine the appropriate amount of CN-105 drug product to administer. Estimated weight may be used if recorded weight is not available. Each dose of CN-105 or placebo will be administered as a slow IV bolus over 30 minutes. Receives: Drug: Acetyl-Valine-Serine-Arginine-Arginine-Arginine-NH2 (Ac-VSRRR- NH2). |
| Placebo arm | Placebo comparator | The Placebo arm will be given 0.9% NaCL Receives: Drug: 0.9% Sodium-chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
adverse event
any untoward medical occurrence associated with the use of the drug in a participant
Measured: 0-12 hours
adverse event
untoward medical occurrence associated with the use of the study drug whether considered related or not
Measured: 24 hour
adverse event
untoward medical occurrence associated with the use of the study drug whether considered related or not
Measured: 48 hour
adverse event
untoward medical occurrence associated with the use of the study drug whether considered related or not
Measured: 72 hour
adverse event
untoward medical occurrence associated wtth the use of study drug whether considered related or not
Measured: 96 hour
adverse event
untoward medical occurrence associated wtth the use of study drug whether considered related or not
Measured: 120 hour
adverse event
untoward medical occurrence associated with the use of study drug whether considered related or not
Measured: 30 day
adverse event
untoward medical occurrence associated with the use of study drug whether considered related or not
Measured: 90 day
GCS
score as per scale
Measured: 0-12 hour
GCS
scored as per scale
Measured: 24H
GCS
scored as per scale
Measured: 48 hours
GCS
scored as per scale
Measured: 72 Hour
GCS
scored as per scale
Measured: 96 hour
GCS
scored as per scale
Measured: at 120 hour
GCS
scored as per scale
Measured: at 30 day
NIHSS
scored as per assessment
Measured: 0- 12 hour
NIHSS
scored as per assessment
Measured: 120 hour
NIHSS
scored as per assessment
Measured: 24 hour
NIHSS
scored as per assessment
Measured: 48 hour
NIHSS
scored as per assessment
Measured: 72 hour
NIHSS
scored as per assessment
Measured: 96 Hour
NIHSS score
score as per assessment
Measured: 30 day
Serious adverse event
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Measured: 48 hour
Serious adverse event
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Measured: 0-12 hour
Serious adverse event
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Measured: 72 hour
Serious adverse event
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Measured: 96 hour
Serious adverse event
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Measured: at 90 day
Serious adverse event
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Measured: at 120 hour
Serious adverse event
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Measured: at 30 day
systemic infection
presence of any infection supported by clinical diagnosis, or any laboratory work up.
Measured: 0-12 hour
systemic infection
presence of any infection supported by clinical diagnosis, or any laboratory work up.
Measured: 24 hour
systemic infection
presence of any infection supported by clinical diagnosis, or any laboratory work up.
Measured: 48 hour
systemic infection
presence of any infection supported by clinical diagnosis, or any laboratory work up.
Measured: 72 hour
systemic infection
presence of any infection supported by clinical diagnosis, or any laboratory work up.
Measured: 96 hours
systemic infection
presence of any infection supported by clinical diagnosis, or any laboratory work up.
Measured: 120 hours
systemic infection
presence of any infection supported by clinical diagnosis, or any laboratory work up.
Measured: 30 day
systemic infection
presence of any infection supported by clinical diagnosis, or any laboratory work up.
Measured: 90 day
Brain CT scan
evaluate hematoma expansion
Measured: 0-12 hour
Brain CT scan
evaluate hematoma expansion
Measured: 24 Hour
presence of CNS infection
meningitis, cerebritis, ventriculitis
Measured: 24 hour
presence of CNS infection
meningitis, cerebritis, ventriculitis
Measured: 72 hours
presence of CNS infection
meningitis, cerebritis, ventriculitis
Measured: 0-12 hour
presence of CNS infection
meningitis, cerebritis, ventriculitis
Measured: 48 hours
presence of CNS infection
meningitis, cerebritis, ventriculitis
Measured: 120 hour
presence of CNS infection
meningitis, cerebritis, ventriculitis
Measured: 96 hour
presence of CNS infection
meningitis, cerebritis, ventriculitis
Measured: 30 day
presence of CNS infection
meningitis, cerebritis, ventriculitis
Measured: 90 day
Mortality
death related or unrelated to the study drug
Measured: 0-12 hour
Mortality
death related or unrelated to the study drug
Measured: 48 hour
Mortality
death related or unrelated to the study drug
Measured: 72 hour
Mortality
death related or unrelated to the study drug
Measured: 24 hour
Mortality
death related or unrelated to the study drug
Measured: 96 hour
Mortality
death related or unrelated to the study drug
Measured: 120 hour
Mortality
occurrence of death related or not related to the use of the study drug
Measured: 30- day
Mortality
occurrence of death related or not related to the use of the study drug
Measured: 90 -day
Secondary outcomes (9)
outcome as assessed by mRS
MRS scoring
Measured: 120 hour
functional outcome as assessed by mRS
MRS scoring
Measured: 30 Day
outcome as assessed by mRS
MRS scoring
Measured: 90Day
cognitive assessment
Montreal cognitive assessment
Measured: 120 Hour
Discharge disposition
The place where the patient was discharge -either home, nursing home or rehabilitation care facilities
Measured: day 90
cognitive assessment
Montreal cognitive assessment
Measured: 30 day
Barthel index
score as per assessment
Measured: 120 hour
Barthel index
score as per assessment
Measured: 30 day
Barthel index
score as per assessment
Measured: 90 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2018
- Study start24 Mar 2019
- Primary completion16 Jun 2022
- Study completion16 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Intracerebral HemorrhageStudies 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 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The treatment arm will be given CN 105 The placebo arm will be give 0/9% NaCl
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Neuroscience Institute
- Sponsor type
- University, hospital or other
- Collaborators
- AegisCN LLC, Singapore Clinical Research Institute
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03711903
- Sponsor's protocol ID
- S-CATCH
- Acronym
- S-CATCH
- Status last verified
- Nov 2022
- First submitted
- 28 Sep 2018
- Last updated
- 1 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Li N, Liu YF, Ma L, Worthmann H, Wang YL, Wang YJ, Gao YP, Raab P, Dengler R, Weissenborn K, Zhao XQ. Association of molecular markers with perihematomal edema and clinical outcome in intracerebral hemorrhage. Stroke. 2013 Mar;44(3):658-63. doi: 10.1161/STROKEAHA.112.673590. Epub 2013 Feb 6.
PubMed 23391772Lynch JR, Pineda JA, Morgan D, Zhang L, Warner DS, Benveniste H, Laskowitz DT. Apolipoprotein E affects the central nervous system response to injury and the development of cerebral edema. Ann Neurol. 2002 Jan;51(1):113-7. doi: 10.1002/ana.10098.
PubMed 11782990Lynch JR, Wang H, Mace B, Leinenweber S, Warner DS, Bennett ER, Vitek MP, McKenna S, Laskowitz DT. A novel therapeutic derived from apolipoprotein E reduces brain inflammation and improves outcome after closed head injury. Exp Neurol. 2005 Mar;192(1):109-16. doi: 10.1016/j.expneurol.2004.11.014.
PubMed 15698624Wang J, Dore S. Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab. 2007 May;27(5):894-908. doi: 10.1038/sj.jcbfm.9600403. Epub 2006 Oct 11.
PubMed 17033693Gao J, Wang H, Sheng H, Lynch JR, Warner DS, Durham L, Vitek MP, Laskowitz DT. A novel apoE-derived therapeutic reduces vasospasm and improves outcome in a murine model of subarachnoid hemorrhage. Neurocrit Care. 2006;4(1):25-31. doi: 10.1385/NCC:4:1:025.
PubMed 16498192Aono M, Bennett ER, Kim KS, Lynch JR, Myers J, Pearlstein RD, Warner DS, Laskowitz DT. Protective effect of apolipoprotein E-mimetic peptides on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cell cultures. Neuroscience. 2003;116(2):437-45. doi: 10.1016/s0306-4522(02)00709-1.
PubMed 12559098Gebel JM Jr, Jauch EC, Brott TG, Khoury J, Sauerbeck L, Salisbury S, Spilker J, Tomsick TA, Duldner J, Broderick JP. Relative edema volume is a predictor of outcome in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke. 2002 Nov;33(11):2636-41. doi: 10.1161/01.str.0000035283.34109.ea.
PubMed 12411654Carhuapoma JR, Barker PB, Hanley DF, Wang P, Beauchamp NJ. Human brain hemorrhage: quantification of perihematoma edema by use of diffusion-weighted MR imaging. AJNR Am J Neuroradiol. 2002 Sep;23(8):1322-6.
PubMed 12223372Guptill JT, Raja SM, Boakye-Agyeman F, Noveck R, Ramey S, Tu TM, Laskowitz DT. Phase 1 Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety, Tolerability, and Pharmacokinetics of a Single Escalating Dose and Repeated Doses of CN-105 in Healthy Adult Subjects. J Clin Pharmacol. 2017 Jun;57(6):770-776. doi: 10.1002/jcph.853. Epub 2016 Dec 19.
PubMed 27990643Laskowitz DT, Goel S, Bennett ER, Matthew WD. Apolipoprotein E suppresses glial cell secretion of TNF alpha. J Neuroimmunol. 1997 Jun;76(1-2):70-4. doi: 10.1016/s0165-5728(97)00021-0.
PubMed 9184634Lei B, James ML, Liu J, Zhou G, Venkatraman TN, Lascola CD, Acheson SK, Dubois LG, Laskowitz DT, Wang H. Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage. Sci Rep. 2016 Oct 7;6:34834. doi: 10.1038/srep34834.
PubMed 27713572Misra UK, Adlakha CL, Gawdi G, McMillian MK, Pizzo SV, Laskowitz DT. Apolipoprotein E and mimetic peptide initiate a calcium-dependent signaling response in macrophages. J Leukoc Biol. 2001 Oct;70(4):677-83.
PubMed 11590206Laskowitz DT, Wang H, Chen T, Lubkin DT, Cantillana V, Tu TM, Kernagis D, Zhou G, Macy G, Kolls BJ, Dawson HN. Neuroprotective pentapeptide CN-105 is associated with reduced sterile inflammation and improved functional outcomes in a traumatic brain injury murine model. Sci Rep. 2017 Apr 21;7:46461. doi: 10.1038/srep46461.
PubMed 28429734Laskowitz DT, Thekdi AD, Thekdi SD, Han SK, Myers JK, Pizzo SV, Bennett ER. Downregulation of microglial activation by apolipoprotein E and apoE-mimetic peptides. Exp Neurol. 2001 Jan;167(1):74-85. doi: 10.1006/exnr.2001.7541.
PubMed 11161595Laskowitz DT, Blessing R, Floyd J, White WD, Lynch JR. Panel of biomarkers predicts stroke. Ann N Y Acad Sci. 2005 Aug;1053:30. doi: 10.1196/annals.1344.051. No abstract available.
PubMed 16179504
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double Blind, Placebo , Controlled Study To Evaluate The Administration of CN-105 In Participants With Acute Supratentorial Intracerebral Hemorrhage
- ClinicalTrials.gov ID
- NCT03711903
- Acronym / sponsor ID
- S-CATCH / S-CATCH
- Conditions
- Intracerebral Hemorrhage
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Neuroscience InstituteUniversity, hospital or other
- Collaborators
- AegisCN LLC, Singapore Clinical Research Institute
- Study start
- 24 Mar 2019 (actual)
- Primary completion
- 16 Jun 2022 (actual)
- Study completion
- 16 Jun 2022 (actual)
- First posted
- 19 Oct 2018 (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.
Phase 2, randomized, double-blind, placebo controlled study to evaluate the administration of CN-105 in patients with supratentorial intracerebral hemorrhage (ICH). Patients will be evaluated for eligibility within 12 hours of symptom onset. Eligible participants (30 active participants and 30 control participants) will receive CN-105 or placebo administered intravenously (IV) for a 30-minute infusion every 6 hours for up to a maximum of 3 days (13 doses) or until discharge (if earlier than 3 days). Participants will be monitored daily throughout the Treatment phase of the study (up to a maximum of 5 days) and will receive standard-of-care treatment for the duration of the study. Additional protocol assessments will be required during the Treatment phase as outlined in Section 7.5. After discharge from the hospital, participants will enter a 3-month Follow-up phase, with a clinic visit at 30 days and a follow-up telephone interview with telephone-validated mRS at 90 days after first dose of study agent.
Detailed description
Phase 2, randomized, double-blind, placebo controlled study to evaluate the administration of CN-105 in patients with supratentorial intracerebral hemorrhage (ICH). Patients will be evaluated for eligibility within 12 hours of symptom onset. Eligible participants (30 active participants and 30 control participants) will receive CN-105 or placebo administered intravenously (IV) for a 30-minute infusion every 6 hours for up to a maximum of 3 days (13 doses) or until discharge (if earlier than 3 days). Participants will be monitored daily throughout the Treatment phase of the study (up to a maximum of 5 days) and will receive standard-of-care treatment for the duration of the study. Additional protocol assessments will be required during the Treatment phase as outlined in Section 7.5. After discharge from the hospital, participants will enter a 3-month Follow-up phase, with a clinic visit at 30 days and a follow-up telephone interview with telephone-validated mRS at 90 days after first dose of study agent.
The study is not powered to test any specific hypothesis in regard to safety and will instead use descriptive methods to describe the experience of the study cohort with respect to adverse and serious adverse events (SAEs), as well as the occurrence of several pre-specified events of interest. The secondary objective of this study will be met by comparing the modified Rankin score (mRS) at 30 days between participants treated with CN-105 with placebo controlled participants The mRS at 30 days will be compared between treated and control participants using the Wilcoxon rank sum test. Exploratory analyses include comparison of treated and control participants for radiographic cerebral edema and hematoma volume and expansion and biological markers of inflammation.
Primary: To assess safety of CN-105 administration in primary ICH.
Secondary: To evaluate whether the administration of CN-105 improves 30-day mortality and functional outcomes by comparing participants treated with CN-105 with placebo controlled participants.
Exploratory:
- To investigate feasibility of Day 0, 1, 2, and 5 non-contrast head computed tomography (CT) as a radiographic surrogate to evaluate progression of perihematomal edema
- To investigate feasibility of using serial biochemical markers of neuroinflammation and neuronal injury as a surrogate measure of perihematomal edema and clinical outcome in the setting of spontaneous ICH.Primary:
- Number and severity of AEs throughout the duration of the study
- Number and severity of SAEs throughout the duration of the study
- In-hospital, 30-day, and 90-day mortality
- Treatment-related mortality
- In-hospital neurological deterioration, defined as an increase of National Institutes of Health Stroke Scale (NIHSS), > 2 from baseline and/or decrease of > 2 of Glasgow Coma Scale (GCS), persisting more than 24 hours, and unrelated to sedation
- Incidence of cerebritis, meningitis, ventriculitis
- Incidence of systemic infection
- Incidence of hematoma extension Secondary:.
- 30- and 90-day mRS
- Need for intracranial hypertension management
- NIHSS score, Glasgow Coma Scale, Montreal Cognitive Assessment, Stroke Impact Scale-16, and Barthel Index assessment at hospital discharge and 30 days after ICH
- Discharge disposition
Exploratory:
- Day 0, 1, 2, 5 non-contrast head CT as a radiographic surrogate to evaluate progression of perihematomal edema
- Biochemical surrogates of brain injury, including plasma concentrations of S100B, glial fibrillary acidic protein, metalloproteinase-3 and -9, C-reactive protein, D-dimer, brain natriuretic peptide, interleukin-6, tumor necrosis factor-α, and vascular endothelial growth factor, assessed daily for 5 days after ICH or until discharge (concentration time area under the curve assessed for each biomarker)
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The treatment arm will be given CN 105 The placebo arm will be give 0/9% NaCl
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: Acetyl-Valine-Serine-Arginine-Arginine-Arginine-NH2 (Ac-VSRRR- NH2).The study drug, CN-105, will be administered at 1.0 mg/kg every 6 +/- 1 hour. The calculated volumes of study agent will be removed from the vials and transferred to 250 mL of normal saline (0.9% sodium chloride injection, USP). The recorded weight at baseline will be used to determine the appropriate amount of CN-105 drug product to administer. Estimated weight may be used if recorded weight is not available. Each dose of CN-105 or placebo will be administered as a slow IV bolus over 30 minutes. |
| Placebo arm | Placebo comparator | Drug: 0.9% Sodium-chlorideThe Placebo arm will be given 0.9% NaCL |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Has given written informed consent to participate in the study in accordance with required regulations; if a participant is not capable of providing informed consent, written consent must be obtained from the participant's legally authorized representative (LAR).
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Is male or female, age 30 to 80 years, inclusive.
- Has a confirmed diagnosis of spontaneous supratentorial ICH.
- Able to receive first dose of study drug ≤ 12 hours after onset of ICH symptoms, such as alteration in level of consciousness, severe headache, nausea, vomiting, seizure, and/or focal neurological deficits, or last-known well time.
Key exclusion criteria (8 listed)
- 1Known pregnancy and lactation 2.Has a temperature greater than 38.5°C at Screening. 3.ICH known to result from trauma. 4.Evidence of infratentorial hemorrhage (any involvement of the midbrain or lower brainstem as demonstrated by radiograph or complete third nerve palsy) severely limiting the recovery potential of the patient in the opinion of the investigator.
- 5.Evidence of primary intraventricular hemorrhage deemed to be at high risk for obstructive hydrocephalus, in the opinion of the investigator or evidence of extra-axial (i.e., subarachnoid or subdural) extension of hemorrhage severely limiting the recovery potential of the patient in the opinion of the investigator.
- 6.Radiographic evidence of underlying tumor. 7.Known unstable mass or active radiographic evidence and symptoms of herniation syndromes severely limiting the recovery potential of the patient in the opinion of the investigator.
- 8.Known ruptured aneurysm, arteriovenous malformation, or vascular anomaly. 9.Has a platelet count < 100,000/mL. 10.Has an international normalized ratio (INR) > 1.5 or irreversible coagulopathy either due to medical condition or detected before screening.
- 11.Is taking new oral anticoagulants (NOACS) or low molecular weight heparin at the time of ICH onset 12.In the opinion of the investigator is unstable and would benefit from supportive care rather than supportive care plus CN-105.
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 |
|---|---|---|
| Acetyl-Valine-Serine-Arginine-Arginine-Arginine-NH2 (Ac-VSRRR- NH2).Also: CN105The study drug, CN-105 is supplied in amber glass vials containing 4 mL of a concentrated 12.5-mg/mL clear-to-slightly-yellow solution. | Drug | Treatment arm |
| 0.9% Sodium-chloridenormal saline | Drug | Placebo arm |
Primary outcome
adverse event
Time frame: 0-12 hours
any untoward medical occurrence associated with the use of the drug in a participant
adverse event
Time frame: 24 hour
untoward medical occurrence associated with the use of the study drug whether considered related or not
adverse event
Time frame: 48 hour
untoward medical occurrence associated with the use of the study drug whether considered related or not
adverse event
Time frame: 72 hour
untoward medical occurrence associated with the use of the study drug whether considered related or not
adverse event
Time frame: 96 hour
untoward medical occurrence associated wtth the use of study drug whether considered related or not
adverse event
Time frame: 120 hour
untoward medical occurrence associated wtth the use of study drug whether considered related or not
adverse event
Time frame: 30 day
untoward medical occurrence associated with the use of study drug whether considered related or not
adverse event
Time frame: 90 day
untoward medical occurrence associated with the use of study drug whether considered related or not
GCS
Time frame: 0-12 hour
score as per scale
GCS
Time frame: 24H
scored as per scale
GCS
Time frame: 48 hours
scored as per scale
GCS
Time frame: 72 Hour
scored as per scale
GCS
Time frame: 96 hour
scored as per scale
GCS
Time frame: at 120 hour
scored as per scale
GCS
Time frame: at 30 day
scored as per scale
NIHSS
Time frame: 0- 12 hour
scored as per assessment
NIHSS
Time frame: 120 hour
scored as per assessment
NIHSS
Time frame: 24 hour
scored as per assessment
NIHSS
Time frame: 48 hour
scored as per assessment
NIHSS
Time frame: 72 hour
scored as per assessment
NIHSS
Time frame: 96 Hour
scored as per assessment
NIHSS score
Time frame: 30 day
score as per assessment
Serious adverse event
Time frame: 48 hour
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Serious adverse event
Time frame: 0-12 hour
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Serious adverse event
Time frame: 72 hour
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Serious adverse event
Time frame: 96 hour
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Serious adverse event
Time frame: at 90 day
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Serious adverse event
Time frame: at 120 hour
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
Serious adverse event
Time frame: at 30 day
An AE is considered serious if the investigator believes any of the following outcomes may occur: death, life threatening AE which places participants at immediate risk of death at the time of the event as it occurred, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; Congenital abnormality or birth defect ;Requires inpatient hospitalization or prolongation of existing hospitalization with the exception or preplanned (before the study) hospital admissions, planned admissions, hospitalization of less then 24 hours (after discharge from index hospitalization.
systemic infection
Time frame: 0-12 hour
presence of any infection supported by clinical diagnosis, or any laboratory work up.
systemic infection
Time frame: 24 hour
presence of any infection supported by clinical diagnosis, or any laboratory work up.
systemic infection
Time frame: 48 hour
presence of any infection supported by clinical diagnosis, or any laboratory work up.
systemic infection
Time frame: 72 hour
presence of any infection supported by clinical diagnosis, or any laboratory work up.
systemic infection
Time frame: 96 hours
presence of any infection supported by clinical diagnosis, or any laboratory work up.
systemic infection
Time frame: 120 hours
presence of any infection supported by clinical diagnosis, or any laboratory work up.
systemic infection
Time frame: 30 day
presence of any infection supported by clinical diagnosis, or any laboratory work up.
systemic infection
Time frame: 90 day
presence of any infection supported by clinical diagnosis, or any laboratory work up.
Brain CT scan
Time frame: 0-12 hour
evaluate hematoma expansion
Brain CT scan
Time frame: 24 Hour
evaluate hematoma expansion
presence of CNS infection
Time frame: 24 hour
meningitis, cerebritis, ventriculitis
presence of CNS infection
Time frame: 72 hours
meningitis, cerebritis, ventriculitis
presence of CNS infection
Time frame: 0-12 hour
meningitis, cerebritis, ventriculitis
presence of CNS infection
Time frame: 48 hours
meningitis, cerebritis, ventriculitis
presence of CNS infection
Time frame: 120 hour
meningitis, cerebritis, ventriculitis
presence of CNS infection
Time frame: 96 hour
meningitis, cerebritis, ventriculitis
presence of CNS infection
Time frame: 30 day
meningitis, cerebritis, ventriculitis
presence of CNS infection
Time frame: 90 day
meningitis, cerebritis, ventriculitis
Mortality
Time frame: 0-12 hour
death related or unrelated to the study drug
Mortality
Time frame: 48 hour
death related or unrelated to the study drug
Mortality
Time frame: 72 hour
death related or unrelated to the study drug
Mortality
Time frame: 24 hour
death related or unrelated to the study drug
Mortality
Time frame: 96 hour
death related or unrelated to the study drug
Mortality
Time frame: 120 hour
death related or unrelated to the study drug
Mortality
Time frame: 30- day
occurrence of death related or not related to the use of the study drug
Mortality
Time frame: 90 -day
occurrence of death related or not related to the use of the study drug
9 secondary outcomes
outcome as assessed by mRS
Time frame: 120 hour
functional outcome as assessed by mRS
Time frame: 30 Day
outcome as assessed by mRS
Time frame: 90Day
cognitive assessment
Time frame: 120 Hour
Discharge disposition
Time frame: day 90
cognitive assessment
Time frame: 30 day
Barthel index
Time frame: 120 hour
Barthel index
Time frame: 30 day
Barthel index
Time frame: 90 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2022.
- Background: PubMed 23391772Li N, Liu YF, Ma L, Worthmann H, Wang YL, Wang YJ, Gao YP, Raab P, Dengler R, Weissenborn K, Zhao XQ. Association of molecular markers with perihematomal edema and clinical outcome in intracerebral hemorrhage. Stroke. 2013 Mar;44(3):658-63. doi: 10.1161/STROKEAHA.112.673590. Epub 2013 Feb 6.
- Background: PubMed 11782990Lynch JR, Pineda JA, Morgan D, Zhang L, Warner DS, Benveniste H, Laskowitz DT. Apolipoprotein E affects the central nervous system response to injury and the development of cerebral edema. Ann Neurol. 2002 Jan;51(1):113-7. doi: 10.1002/ana.10098.
- Background: PubMed 15698624Lynch JR, Wang H, Mace B, Leinenweber S, Warner DS, Bennett ER, Vitek MP, McKenna S, Laskowitz DT. A novel therapeutic derived from apolipoprotein E reduces brain inflammation and improves outcome after closed head injury. Exp Neurol. 2005 Mar;192(1):109-16. doi: 10.1016/j.expneurol.2004.11.014.
- Background: PubMed 17033693Wang J, Dore S. Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab. 2007 May;27(5):894-908. doi: 10.1038/sj.jcbfm.9600403. Epub 2006 Oct 11.
- Background: PubMed 16498192Gao J, Wang H, Sheng H, Lynch JR, Warner DS, Durham L, Vitek MP, Laskowitz DT. A novel apoE-derived therapeutic reduces vasospasm and improves outcome in a murine model of subarachnoid hemorrhage. Neurocrit Care. 2006;4(1):25-31. doi: 10.1385/NCC:4:1:025.
- Background: PubMed 12559098Aono M, Bennett ER, Kim KS, Lynch JR, Myers J, Pearlstein RD, Warner DS, Laskowitz DT. Protective effect of apolipoprotein E-mimetic peptides on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cell cultures. Neuroscience. 2003;116(2):437-45. doi: 10.1016/s0306-4522(02)00709-1.
- Background: PubMed 12411654Gebel JM Jr, Jauch EC, Brott TG, Khoury J, Sauerbeck L, Salisbury S, Spilker J, Tomsick TA, Duldner J, Broderick JP. Relative edema volume is a predictor of outcome in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke. 2002 Nov;33(11):2636-41. doi: 10.1161/01.str.0000035283.34109.ea.
- Background: PubMed 12223372Carhuapoma JR, Barker PB, Hanley DF, Wang P, Beauchamp NJ. Human brain hemorrhage: quantification of perihematoma edema by use of diffusion-weighted MR imaging. AJNR Am J Neuroradiol. 2002 Sep;23(8):1322-6.
- Results publication: PubMed 27990643Guptill JT, Raja SM, Boakye-Agyeman F, Noveck R, Ramey S, Tu TM, Laskowitz DT. Phase 1 Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety, Tolerability, and Pharmacokinetics of a Single Escalating Dose and Repeated Doses of CN-105 in Healthy Adult Subjects. J Clin Pharmacol. 2017 Jun;57(6):770-776. doi: 10.1002/jcph.853. Epub 2016 Dec 19.
- Results publication: PubMed 9184634Laskowitz DT, Goel S, Bennett ER, Matthew WD. Apolipoprotein E suppresses glial cell secretion of TNF alpha. J Neuroimmunol. 1997 Jun;76(1-2):70-4. doi: 10.1016/s0165-5728(97)00021-0.
- Results publication: PubMed 27713572Lei B, James ML, Liu J, Zhou G, Venkatraman TN, Lascola CD, Acheson SK, Dubois LG, Laskowitz DT, Wang H. Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage. Sci Rep. 2016 Oct 7;6:34834. doi: 10.1038/srep34834.
- Results publication: PubMed 11590206Misra UK, Adlakha CL, Gawdi G, McMillian MK, Pizzo SV, Laskowitz DT. Apolipoprotein E and mimetic peptide initiate a calcium-dependent signaling response in macrophages. J Leukoc Biol. 2001 Oct;70(4):677-83.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acetyl-Valine-Serine-Arginine-Arginine-Arginine-NH2 (Ac-VSRRR- NH2). and 0.9% Sodium-chloride in people with Intracerebral Hemorrhage, run by National Neuroscience Institute at 1 site in Singapore.
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 9 inclusion and 8 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: finished, as of the sponsor's last update on 1 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. 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 phase mean?
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
adverse event (time frame: 0-12 hours). The study lists 55 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03711903, which also lists 17 linked publications.
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 1 Dec 2022.