Intracerebral Hemorrhage (ICH)Phase 1NCT02670824
Safety Study of CN-105 Neuroprotective Peptide for Intracerebral Hemorrhage
A Phase 1 study testing CN-105 in people with Intracerebral Hemorrhage (ICH), run by AegisCN LLC at 1 site in United States.
Trial summary
This study evaluates the safety, tolerability, and pharmacokinetics (PK) of a single escalating dose and repeated doses of CN-105 in healthy adult participants. There will be about 48 subjects, 36 active and 12 placebo. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Intracerebral Hemorrhage (ICH)
- What is being tested?
- CN-105
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to Aug 2016
- Phase
- Phase 1
- 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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Capable of giving written Informed Consent to participate in the study prior to undergoing any screening procedures.
- Non-smoking and does not use nicotine-containing products (including smoking cessation aids, such as gums or patches) for 6 months or greater at study commencement
- Adult male or female volunteers between 18 and 50 years (inclusive) at screening
- BMI between 18-33 kg/m2 (inclusive) and weighing at least 110 lbs (50 kg).
- Healthy on the basis of the medical history, physical examination, vital signs, ECG, blood chemistry, hematology, and urinalysis performed at screening.
- Adequate peripheral forearm vein access.
Show all 16Show fewer
- No significant dietary restrictions and willing to fully consume all Duke CRU "Regular Diet" meals and beverages/water provided to them.
- No prescription medication except contraception as described in Inclusion #10 within 7 days or 5 half-lives (whichever is longer) of study entry (randomization and initiation of study drug administration) or any over-the-counter (OTC) medication or herbal/vitamin supplement within 7 days of study entry, and not expected to require or take any prescription or over-the-counter medication or supplement for the full duration of the study. Acetaminophen at doses of ≤1 g/day may be used and stable treatment for seasonal allergies (other than glucocorticoids via any route) may be used. Limited use of non-prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case by case basis following approval by the sponsor.
- Women who are of non-childbearing potential, must be:
- Surgically sterile (removal of both ovaries and/ or uterus at least 12 months prior to dosing).
- Naturally postmenopausal (spontaneous cessation of menses) for at least 24 consecutive months prior to dosing on Day -1 and with an FSH level at screening of ≥ 40 mIU/mL.
- Women of child-bearing potential must have a negative serum pregnancy test at screening and urine pregnancy test during the study, and must agree to avoid pregnancy during study and for three months after the last dose of study drug. Pregnancy is tested at screening, during check-in, during the follow-up visit, and at any given point if deemed necessary to the PI or designate. During treatment, women of child-bearing potential must use two acceptable methods of contraception at the same time unless the subject has had a documented tubal sterilization or chooses to use a Copper T 380A IUD or LNG 20 IUS, in which case no additional contraception is required. Medically acceptable contraceptives include: (1) documented surgical sterilization (such as a hysterectomy), (2) barrier methods (such as a condom or diaphragm) used with a spermicide, (3) hormonal contraception (combination oral contraceptives, transdermal patch, injectables, implantables, or vaginal ring) or (4) an intrauterine device (IUD) or intrauterine system (IUS). Abstinence is not an acceptable form of contraception in this study.
- Male participants must agree to take all necessary measures to avoid causing pregnancy in their sexual partners during the study and for three months after the last dose of study drug. Medically acceptable contraceptives include: (1) surgical sterilization (such as a vasectomy), or (2) a condom used with a spermicidal. Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use.
- Must not have donated blood, platelets, or any other blood components 30 days, or plasma 90 days, prior to consenting. Must also agree not to donate blood, platelets, or any other blood components for 3 months after the last dose of study drug.
- Male participants must agree not to donate sperm during the study and for 12 weeks after the last dose.
- Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
Who cannot join
- Laboratory results outside the normal range, if considered clinically significant (CS) by the PI or delegate. Any laboratory result outside the normal range and not clinically significant will be designated as such by NCS (Non-clinically Significant).
- Mental capacity that is limited to the extent that the participant cannot provide legal consent or understand information regarding the side effects of the study drug.
- Currently abusing drugs or alcohol or with a history of drug or alcohol abuse within the past two years or drinks more than 3 cups of coffee per day.
- Unwillingness or lack of ability to comply with the protocol, or to cooperate fully with the PI and site personnel.
- Clinically significant ECG abnormality in the opinion of the PI or delegate.
- Has taken any other investigational drug during the 30 days or 5 half-lives (whichever is longer) prior to the screening visit or is currently participating in another investigational drug clinical trial.
Show all 12Show fewer
- History or manifestation of clinically significant neurological (e.g., frequent headaches or migraines), gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematologic or other medical disorders that might influence the interpretation of the results of the study.
- Infected with Hepatitis B or C or HIV Virus.
- Participants who have a history of unexplained syncope or fainting from the collection of blood; i.e., autonomic dysfunction.
- Lack of ability to understand verbal and/ or written English
- Subjects who had significant trauma or surgical procedure within 1 month prior to Screening.
- A positive urine drug screen or positive alcohol breathalyzer test.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke Clinical Research Institute
Durham, North Carolina, 27705
About this study
Official title: Study to Determine the Safety, Tolerability, and Pharmacokinetics of a Single Escalating Dose and Repeated Doses of CN-105 in Healthy Adult Subjects
This study evaluates the safety, tolerability, and pharmacokinetics (PK) of a single escalating dose and repeated doses of CN-105 in healthy adult participants. There will be about 48 subjects, 36 active and 12 placebo.
Read the detailed description
Intracerebral hemorrhage (ICH), which is often associated with longstanding hypertension, affects as many as 50,000 people annually in the United States alone. ICH remains associated with poor outcome, and approximately 40 to 50% of afflicted patients will die within 30 days. Unfortunately, little improvement has been made in the ICH-associated mortality rate over the last 20 years. To address this issue, the National Institutes of Health issued a priorities report in 2005, and the American Heart Association released a recent set of clinical guidelines for the first time in nearly a decade. In these reports, the importance of developing clinically relevant models of ICH that will extend our understanding of the pathophysiology of the disease and target new therapeutic approaches was emphasized. At present, however, there are no proven neuroprotective pharmacological treatments for ICH or other forms of acute brain injuries, such as traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH).
To meet this unmet medical need, CereNova, LLC has developed a novel therapeutic approach based on the known biological function of endogenous apolipoprotein E (apoE), a key mediator of the neuroinflammatory response and recovery from a variety of acute and chronic brain injuries1-5. There are three common human isoforms of apolipoprotein E, designated apoE2, apoE3, and apoE4, which differ by single cysteine to arginine substitutions at positions 112 and 158. Although originally defined in the context of cholesterol metabolism, apoE is also produced in the brain, where it modulates neuroinflammatory responses and functional outcomes after injury in an isoform specific fashion1. Specifically, the apoE3 protein isoform plays an adaptive role in downregulating glial activation and reducing secondary neuronal injury, whereas the E4 isoform is associated with increased neuroinflammation and poor functional outcomes.
Although the intact apoE holoprotein does not cross the blood brain barrier (BBB) and thus cannot be administered therapeutically, we have previously demonstrated that smaller apoE mimetic peptides do effectively cross the BBB while effectively downregulating the brain inflammatory responses in vitro and in vivo6. CN-105, CereNova's lead clinical candidate, is a small, 5 amino acid apoE-mimetic peptide that is derived from the receptor binding region of apoE. CN-105 retains the anti-inflammatory and neuroprotective effects of intact apoE, is well tolerated in preclinical studies, and readily crosses the BBB to effectively reduce inflammatory responses in the brain.
- Conditions
- Intracerebral Hemorrhage (ICH)
- Being tested
- CN-105, Placebo
- Medical subject headings
- Cerebral Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CN-105Drug
Single and multiple intravenous (IV) doses of CN-105
PlaceboDrug
Normal Saline
| Study group | Role | What they receive |
|---|---|---|
| CN-105 Active Drug | Experimental | The CN-105 drug administered via IV at an escalating scale of mg/kg.
A1-0.01 mg/kg A2-0.03 mg/kg A3-0.1 mg/kg A4-0.3 mg/kg A5-1.0 mg/kg B1-1.0 mg/kg Receives: Drug: CN-105 |
| Placebo | Placebo comparator | Normal Saline Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number and percentage of participants having study procedure-related suspected adverse reactions assessed by change from baseline in vital signs, ECG and clinical labs.
The number and percentage of participants having study procedure-related suspected adverse reactions assessed by change from baseline in vital signs, ECG and clinical labs will be tabulated and evaluated
Measured: up to 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2016 (estimated)
- Study startDec 2015
- Primary completionMay 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Intracerebral Hemorrhage (ICH)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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- AegisCN LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02670824
- Sponsor's protocol ID
- CN-105-01
- Status last verified
- Aug 2016
- First submitted
- 7 Jan 2016
- Last updated
- 18 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Li S, Wangqin R, Meng X, Li H, Wang Y, Wang H, Laskowitz D, Chen X, Wang Y. Tolerability and Pharmacokinetics of Single Escalating and Repeated Doses of CN-105 in Healthy Participants. Clin Ther. 2022 May;44(5):744-754. doi: 10.1016/j.clinthera.2022.03.006. Epub 2022 May 11.
PubMed 35562205
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Determine the Safety, Tolerability, and Pharmacokinetics of a Single Escalating Dose and Repeated Doses of CN-105 in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT02670824
- Acronym / sponsor ID
- CN-105-01
- Conditions
- Intracerebral Hemorrhage (ICH)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- AegisCN LLCIndustry (pharma, biotech, devices)
- Study start
- Dec 2015
- Primary completion
- May 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 2 Feb 2016 (estimated)
- 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.
This study evaluates the safety, tolerability, and pharmacokinetics (PK) of a single escalating dose and repeated doses of CN-105 in healthy adult participants. There will be about 48 subjects, 36 active and 12 placebo.
Detailed description
Intracerebral hemorrhage (ICH), which is often associated with longstanding hypertension, affects as many as 50,000 people annually in the United States alone. ICH remains associated with poor outcome, and approximately 40 to 50% of afflicted patients will die within 30 days. Unfortunately, little improvement has been made in the ICH-associated mortality rate over the last 20 years. To address this issue, the National Institutes of Health issued a priorities report in 2005, and the American Heart Association released a recent set of clinical guidelines for the first time in nearly a decade. In these reports, the importance of developing clinically relevant models of ICH that will extend our understanding of the pathophysiology of the disease and target new therapeutic approaches was emphasized. At present, however, there are no proven neuroprotective pharmacological treatments for ICH or other forms of acute brain injuries, such as traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH).
To meet this unmet medical need, CereNova, LLC has developed a novel therapeutic approach based on the known biological function of endogenous apolipoprotein E (apoE), a key mediator of the neuroinflammatory response and recovery from a variety of acute and chronic brain injuries1-5. There are three common human isoforms of apolipoprotein E, designated apoE2, apoE3, and apoE4, which differ by single cysteine to arginine substitutions at positions 112 and 158. Although originally defined in the context of cholesterol metabolism, apoE is also produced in the brain, where it modulates neuroinflammatory responses and functional outcomes after injury in an isoform specific fashion1. Specifically, the apoE3 protein isoform plays an adaptive role in downregulating glial activation and reducing secondary neuronal injury, whereas the E4 isoform is associated with increased neuroinflammation and poor functional outcomes.
Although the intact apoE holoprotein does not cross the blood brain barrier (BBB) and thus cannot be administered therapeutically, we have previously demonstrated that smaller apoE mimetic peptides do effectively cross the BBB while effectively downregulating the brain inflammatory responses in vitro and in vivo6. CN-105, CereNova's lead clinical candidate, is a small, 5 amino acid apoE-mimetic peptide that is derived from the receptor binding region of apoE. CN-105 retains the anti-inflammatory and neuroprotective effects of intact apoE, is well tolerated in preclinical studies, and readily crosses the BBB to effectively reduce inflammatory responses in the brain.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CN-105 Active Drug | Experimental | Drug: CN-105The CN-105 drug administered via IV at an escalating scale of mg/kg. A1-0.01 mg/kg A2-0.03 mg/kg A3-0.1 mg/kg A4-0.3 mg/kg A5-1.0 mg/kg B1-1.0 mg/kg |
| Placebo | Placebo comparator | Drug: PlaceboNormal Saline |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- Capable of giving written Informed Consent to participate in the study prior to undergoing any screening procedures.
- Non-smoking and does not use nicotine-containing products (including smoking cessation aids, such as gums or patches) for 6 months or greater at study commencement
- Adult male or female volunteers between 18 and 50 years (inclusive) at screening
- BMI between 18-33 kg/m2 (inclusive) and weighing at least 110 lbs (50 kg).
- Healthy on the basis of the medical history, physical examination, vital signs, ECG, blood chemistry, hematology, and urinalysis performed at screening.
Key exclusion criteria (12 listed)
- Laboratory results outside the normal range, if considered clinically significant (CS) by the PI or delegate. Any laboratory result outside the normal range and not clinically significant will be designated as such by NCS (Non-clinically Significant).
- Mental capacity that is limited to the extent that the participant cannot provide legal consent or understand information regarding the side effects of the study drug.
- Currently abusing drugs or alcohol or with a history of drug or alcohol abuse within the past two years or drinks more than 3 cups of coffee per day.
- Unwillingness or lack of ability to comply with the protocol, or to cooperate fully with the PI and site personnel.
- Clinically significant ECG abnormality in the opinion of the PI or delegate.
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 |
|---|---|---|
| CN-105Single and multiple intravenous (IV) doses of CN-105 | Drug | CN-105 Active Drug |
| PlaceboNormal Saline | Drug | Placebo |
Primary outcome
The number and percentage of participants having study procedure-related suspected adverse reactions assessed by change from baseline in vital signs, ECG and clinical labs.
Time frame: up to 1 week
The number and percentage of participants having study procedure-related suspected adverse reactions assessed by change from baseline in vital signs, ECG and clinical labs will be tabulated and evaluated
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 18 Aug 2016.
- Derived from this study: PubMed 35562205Li S, Wangqin R, Meng X, Li H, Wang Y, Wang H, Laskowitz D, Chen X, Wang Y. Tolerability and Pharmacokinetics of Single Escalating and Repeated Doses of CN-105 in Healthy Participants. Clin Ther. 2022 May;44(5):744-754. doi: 10.1016/j.clinthera.2022.03.006. Epub 2022 May 11.
- Individual participant dataSharing planned: No
Related trials for Intracerebral Hemorrhage (ICH)
RecruitingObservational study
Sleep to Predict Recovery In Unconscious Patients With Acute Brain Injury
Traumatic Brain Injury (TBI) Patients, Intracerebral Hemorrhage (ICH)
Recruiting
TrIal of Early Minimally Invasive Catheter Evacuation With Thrombolysis in IntraCerebral Hemorrhage
Intracerebral Hemorrhage
Not yet recruiting
REmifentanil And Dexmedetomidine for EarlY Intensive Blood Pressure Lowering in ICH.
Intracerebral Hemorrhage
RecruitingObservational study
The Erlanger Stroke Registry (ESPro) is the Only Ongoing Prospective Population-based Stroke Registry in Germany, Started in 1994. ESPro Includes All Hospitalized and Non-hospitalized Patients With Stroke in the Community of Erlangen (120.000 Inhabitants), With a Long-life Follow-up.
Intracerebral Haemorrhage (ICH), Cerebral Infarction
Recruiting
Minimally Invasive Neuroendoscopic Ultra-Early Targeted ICH Evacuation
Basal Ganglia Intracerebral Hemorrhage
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 1 study testing CN-105 in people with Intracerebral Hemorrhage (ICH), run by AegisCN LLC at 1 site 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 16 inclusion and 12 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 18 Aug 2016. 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 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 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.
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?
The number and percentage of participants having study procedure-related suspected adverse reactions assessed by change from baseline in vital signs, ECG and clinical labs. (time frame: up to 1 week). 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 NCT02670824, which also lists 1 linked publication.
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 18 Aug 2016.