Cerebral Cavernous MalformationPhase 1NCT07908134
Study to Establish Safety, Tolerability and Pharmacokinetics of NRL-1049 in Healthy Adult Participants Following Multiple-Dose Administration
A Phase 1 study testing NRL-1049 in people with Cerebral Cavernous Malformation, run by Neurelis, Inc..
Trial summary
This Phase 1, dose-escalation, double-blind, multiple ascending dose (MAD) study was designed to assess the safety and tolerability of NRL-1049 compared to placebo in healthy adult participants and to determine the maximum tolerated dose (MTD) and to assess pharmacokinetics (PK) and dose proportionality. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Cerebral Cavernous Malformation
- What is being tested?
- NRL-1049
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 11 Nov 2026to 26 May 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form (ICF) prior to Screening
- Stated willingness to comply with all study procedures and to follow site and local infectious disease safety protocols, and availability for the duration of the study
- Healthy adult male or female
- If female, meets one of the following criteria:
- Is of childbearing potential and agrees to use an acceptable contraceptive method. Acceptable contraceptive methods include:
- Abstinence from heterosexual intercourse from 14 days prior to the Screening visit through to at least 90 days after the last dose of the study drug
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- One of the following highly-effective contraceptive methods, used from at least 28 days prior to the Screening visit through to at least 90 days after the last dose of the study drug:
- Systemic contraceptives (combined birth control pills, injectable/implant/insertable hormonal birth control products, or transdermal patch)
- Intrauterine device (with or without hormones)
- Male partner vasectomized at least 6 months prior to the Screening visit
- One of the following double-barrier contraceptive methods, used from the Screening visit through to at least 90 days after the last dose of the study drug:
- Male condom plus spermicide, or
- Diaphragm plus spermicide, or
- Cervical cap plus spermicide
- Is of non-childbearing potential, defined as either:
- Surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation), or
- In a postmenopausal state:
- At least 1 year without menses and without an alternative medical condition prior to the Screening visit and follicle-stimulating hormone (FSH) levels ≥ 40 mIU/mL at Screening; or
- At least 1 year without menses and without an alternative medical condition prior to the Screening visit, FSH levels < 40 mIU/mL and estradiol serum level ≤150 pmol/L at Screening
- If male, meets one of the following criteria:
- Is able to procreate and agrees to use one of the accepted contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the last study drug administration. An acceptable method of contraception includes one of the following:
- Abstinence from heterosexual intercourse
- Male condom with spermicide or male condom with a vaginal spermicide (gel, foam, or suppository)
- Is unable to procreate; defined as surgically sterile (i.e., has undergone a vasectomy at least 180 days prior to the first study drug administration)
- Age of at least 18 years but not older than 65 years
- Body mass index within 18.0 to 32.0 kg/m2 (inclusive)
- Body weight between 50 and 111 kg (inclusive)
- Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by an Investigator
- Able to communicate effectively with the study personnel
Who cannot join
- Female who is lactating
- Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration
- History of significant hypersensitivity to ROCK kinase inhibitors or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (e.g., angioedema) to any drugs
- Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability
- Presence or history of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease
- History of surgery or major surgery within 30 days of Screening, or surgery planned during the study
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- Presence of clinically significant ECG abnormalities at the screening visit, as defined by medical judgment (e.g., QTcF > 450 msec for males and >470 msec for females)
- Smoking and the use of tobacco products, tetrahydrocannabinol (THC), or cannabidiol (CBD) in the 6 months prior to the first dose of study drug
- History of alcohol abuse (consumption of >10 standard drinks/week; 1 standard drink is defined as 12 ounces [360 mL] of beer or lager, 5 ounces [150 mL] of wine, or 1.5 ounces [45 mL] of liquor or a mixed drink), illicit drug use, physical dependence to any opiates, THC, CBD, or any history of drug abuse or addiction within 12 months of Screening.
- Any clinically significant illness in the 28 days prior to the first study drug administration
- Use of any prescription drugs (with the exception of hormonal contraceptives or hormone replacement therapy) in the 28 days prior to the first study drug administration, that in the opinion of an Investigator would put into question the status of the participant as healthy
- Use of over-the-counter products, including vitamins and supplements, in the 7 days prior to the first study drug administration
- Use of St. John's wort in the 28 days prior to the first study drug administration
- Treatment with any known drugs that are strong inhibitors of CYP2D6 (such as bupropion, fluoxetine, paroxetine, quinidine, terbinafine, and thioridazine) or substrates of CYP2D6 (such as dextromethorphan, desipramine, atomoxetine, R venlafaxine), within 30 days prior to the first dose of study drug or during the study
- Positive test result for alcohol, cotinine, and/or drugs of abuse at Screening or prior to the first study drug administration
- Positive screening results to HIV antigen/antibody combo, hepatitis B surface antigen, or hepatitis C virus tests
- Any other clinically significant abnormalities in laboratory test results at Screening that would, in the opinion of an Investigator, increase the participant's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data
- Received a dose of the study drug in a previous group for this clinical study
- Intake of another investigational drug within 30 days or 5 half lives of the investigational drug's PK or biological activity (if known), whichever is longer, prior to the first study drug administration of this study
- Any other condition or prior therapy that, in the Investigator's opinion, would make the participant unsuitable for the study, or unable or unwilling to comply with the study procedures
- Donation of plasma in the 7 days prior to the first study drug administration
- Donation of 1 unit of blood to American Red Cross or equivalent organization or donation of over 500 mL of blood in the 56 days prior to the first study drug administration
- Involved in the planning or conduct of this study
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Randomized, Dose-Escalation, Double-Blind, Placebo Controlled, Multiple Ascending Dose Study to Establish Safety, Tolerability and Pharmacokinetics of NRL-1049 in Healthy Adult Participants
This Phase 1, dose-escalation, double-blind, multiple ascending dose (MAD) study was designed to assess the safety and tolerability of NRL-1049 compared to placebo in healthy adult participants and to determine the maximum tolerated dose (MTD) and to assess pharmacokinetics (PK) and dose proportionality. Additionally, changes in blood Rho-associated protein kinase (ROCK) activity levels will be explored.
- Conditions
- Cerebral Cavernous Malformation
- Being tested
- NRL-1049, Placebo
- Medical subject headings
- Hemangioma, Cavernous, Central Nervous System
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NRL-1049Drug
NRL-1049 25 mg and/or 75 mg immediate-release capsules
PlaceboDrug
Placebo-to-match NRL-1049 capsules
| Study group | Role | What they receive |
|---|---|---|
| NRL-1049 50 mg | Active comparator | 2 × 25 mg IR capsules Receives: Drug: NRL-1049 |
| NRL-1049 100 mg | Active comparator | 100 mg: (1 × 25 mg) + (1 x 75 mg) IR capsules Receives: Drug: NRL-1049 |
| NRL-1049 150 mg | Active comparator | 150 mg: 2 × 75 mg IR capsules Receives: Drug: NRL-1049 |
| NRL-1049 200 mg | Active comparator | 200 mg: (2 × 25 mg) + (2 × 75 mg) IR capsules Receives: Drug: NRL-1049 |
| NRL-1049 250 mg | Active comparator | 250 mg: (1 × 25 mg) + (3 × 75 mg) IR capsules Receives: Drug: NRL-1049 |
| Placebo | Placebo comparator | Placebo-to-match NRL-1049 capsules (identical size and appearance as the respective NRL-1049 product strength) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability: Treatment-emergent adverse events (TEAEs)
Measured: Predose on Day 1 until 72 hours following the last study drug administration on Day 7.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2026
- Study start11 Nov 2026 (estimated)
- Primary completion26 May 2027 (estimated)
- Study completion26 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral Cavernous MalformationStudies 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
- Sequential
- Model description
- Up to 5 dose cohorts of 8 participants each will be included in the study. Each participant will receive an oral dose of NRL-1049 or placebo (3:1) once daily for 7 consecutive days under fasting conditions.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Neurelis, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07908134
- Sponsor's protocol ID
- NRL-1049.002
- Status last verified
- Oct 2026
- First submitted
- 14 Oct 2026
- Last updated
- 30 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Dose-Escalation, Double-Blind, Placebo Controlled, Multiple Ascending Dose Study to Establish Safety, Tolerability and Pharmacokinetics of NRL-1049 in Healthy Adult Participants
- ClinicalTrials.gov ID
- NCT07908134
- Acronym / sponsor ID
- NRL-1049.002
- Conditions
- Cerebral Cavernous Malformation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Neurelis, Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Nov 2026 (estimated)
- Primary completion
- 26 May 2027 (estimated)
- Study completion
- 26 May 2027 (estimated)
- First posted
- 30 Oct 2026 (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.
This Phase 1, dose-escalation, double-blind, multiple ascending dose (MAD) study was designed to assess the safety and tolerability of NRL-1049 compared to placebo in healthy adult participants and to determine the maximum tolerated dose (MTD) and to assess pharmacokinetics (PK) and dose proportionality. Additionally, changes in blood Rho-associated protein kinase (ROCK) activity levels will be explored.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
- Model description
- Up to 5 dose cohorts of 8 participants each will be included in the study. Each participant will receive an oral dose of NRL-1049 or placebo (3:1) once daily for 7 consecutive days under fasting conditions.
| Arm | Type | Receives |
|---|---|---|
| NRL-1049 50 mg | Active comparator | Drug: NRL-10492 × 25 mg IR capsules |
| NRL-1049 100 mg | Active comparator | Drug: NRL-1049100 mg: (1 × 25 mg) + (1 x 75 mg) IR capsules |
| NRL-1049 150 mg | Active comparator | Drug: NRL-1049150 mg: 2 × 75 mg IR capsules |
| NRL-1049 200 mg | Active comparator | Drug: NRL-1049200 mg: (2 × 25 mg) + (2 × 75 mg) IR capsules |
| NRL-1049 250 mg | Active comparator | Drug: NRL-1049250 mg: (1 × 25 mg) + (3 × 75 mg) IR capsules |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo-to-match NRL-1049 capsules (identical size and appearance as the respective NRL-1049 product strength) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Provision of signed and dated informed consent form (ICF) prior to Screening
- Stated willingness to comply with all study procedures and to follow site and local infectious disease safety protocols, and availability for the duration of the study
- Healthy adult male or female
- If female, meets one of the following criteria:
- If male, meets one of the following criteria:
Key exclusion criteria (23 listed)
- Female who is lactating
- Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration
- History of significant hypersensitivity to ROCK kinase inhibitors or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (e.g., angioedema) to any drugs
- Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability
- Presence or history of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease
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 |
|---|---|---|
| NRL-1049NRL-1049 25 mg and/or 75 mg immediate-release capsules | Drug | NRL-1049 100 mg, NRL-1049 150 mg, NRL-1049 200 mg, NRL-1049 250 mg, NRL-1049 50 mg |
| PlaceboPlacebo-to-match NRL-1049 capsules | Drug | Placebo |
Primary outcome
Safety and tolerability: Treatment-emergent adverse events (TEAEs)
Time frame: Predose on Day 1 until 72 hours following the last study drug administration on Day 7.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NRL-1049 in people with Cerebral Cavernous Malformation, run by Neurelis, Inc..
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 29 inclusion and 23 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: opening soon, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Miguel A. Lopez-Toledano, PhD ((561) 578 2778, mtoledano@neurelis.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability: Treatment-emergent adverse events (TEAEs) (time frame: Predose on Day 1 until 72 hours following the last study drug administration on Day 7.). 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 30 Oct 2026.