NAFLDPhase 1NCT03261739
Safety Tolerability, and PK of RYI-018 After Repeat Dosing in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)
A Phase 1 study testing RYI-018 in people with NAFLD, run by Bird Rock Bio, Inc. at 6 sites in 3 countries.
Trial summary
BRB-018-001 is a multicenter, adaptive design, randomized, parallel group study to evaluate the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects with NAFLD. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- NAFLD
- What is being tested?
- RYI-018
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 28 Aug 2017to 24 Aug 2018
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult male or females, 18 to 65 years of age (inclusive) at the time of screening.
- BMI ≥25.0 and ≤40.0 (kg/m2) (inclusive).
- Liver ultrasound (or transient elastography if approved by medical monitor) which qualitatively shows fatty liver or documented history of NAFLD.
- Liver fat percentage by MRI of approximately 10% or greater (MRI to be performed only in subjects with documented NAFLD or fatty liver by ultrasound or transient elastography if approved by medical monitor).
- Type 2 diabetes or prediabetes.
- Negative urine drug screen/alcohol breath test at screening.
- Non-smokers as defined by not smoked any tobacco or nicotine-containing products within 3 months prior to screening. No current use of any nicotine containing product.
Who cannot join
- Positive serologic testing for HIV, HBsAg, or HCV.
- Have any known malignancy or history of malignancy, except for basal cell or squamous cell skin cancer that has been treated with no evidence of recurrence for at least 3 months prior to Screening.
- Have any underlying physical or psychological medical condition that, in the opinion of the Investigator or sponsor, would make it unlikely that the subject will complete the study or is not in the subject's best interest
- Liver function tests AST or ALT >5 x ULN at screening. One repeat test may be allowed within 7 days at the discretion of the Investigator.
- Total bilirubin > ULN at screening except in patients with a known history of Gilbert's syndrome.
- History or presence of alcoholism or drug abuse within the 2 years prior to the first study drug administration.
Show all 17Show fewer
- Administration of IP in another trial within 30 Days or 5 times the investigational drug half-life, whichever is longer, prior to the first study drug administration.
- History of cerebrovascular event acute coronary syndrome within 6 months of screening.
- Any history of seizures, major depression, suicidality, or unexplained syncope.
- Subjects with other active (acute or chronic) liver disease other than NAFLD/NASH (e.g., autoimmune liver disease, viral hepatitis, genetic hemochromatosis, Wilson disease, alpha-1-antitrypsin deficiency, alcohol liver disease, drug induced liver disease).
- Use of prescription or non-prescription weight loss medications, thiazolidinediones, investigational or approved medications for NASH, or antidepressant medications within 90 days of screening.
- Use of insulin injections within 30 days of screening.
- History of bariatric surgery or plans for bariatric surgery or an attempt to lose weight during study.
- Daily alcohol intake >20 g/day for women and >30 g/day for men (on average per day), as per medical history.
- Subjects with renal dysfunction estimated glomerular filtration rate <60 mL/min/1.73 m2.
- HbA1c >9.5% at screening.
- Pregnant or breastfeeding women.
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United States4 sites
BRB Site
Chula Vista, California, 91911
BRB Site
Miami, Florida, 33147
BRB Site
Orlando, Florida, 32804
BRB Site
San Antonio, Texas, 78215
About this study
Official title: An Adaptive Design Study for the Assessment of the Safety, Tolerability, and Pharmacokinetics of RYI-018 After Repeat Dosing in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)
BRB-018-001 is a multicenter, adaptive design, randomized, parallel group study to evaluate the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects with NAFLD.
Read the detailed description
BRB-018-001 will be conducted as a multicenter, adaptive design, randomized, parallel group study to evaluate the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects with NAFLD. Subjects in each cohort shall be randomized to either RYI-018 or placebo as weekly injection for four weeks. The active doses of RYI-018 will be as follows: Cohort 1: 0.6 mg/kg, Cohort 2: 1.2 mg/kg, and Cohort 3: 2.5 mg/kg. Primary endpoints include safety and tolerability. Secondary endpoints include pharmacokinetics and immunogenicity.
- Conditions
- NAFLD
- Being tested
- RYI-018, Placebo
- Keywords
- NAFLD, CB1 receptor blockade, anti-CB1 monoclonal antibody
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RYI-018Biological
Anti-CB1 monoclonal antibody
PlaceboBiological
Placebo
| Study group | Role | What they receive |
|---|---|---|
| RYI- 018 | Experimental | The doses of RYI-018 to be evaluated in sequential cohorts will be 0.6 mg/kg, 1.2 mg/kg, and 2.5 mg/kg. Receives: Biological: RYI-018 |
| Placebo | Placebo comparator | vehicle control Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical evaluation of adverse events
Subjects will be assessed for adverse events attributable to RYI-018
Measured: Continuous through 67 days
Secondary outcomes (5)
Time to peak serum concentration
Serum concentrations after single and multiple doses of RYI-018 will be measured and the highest concentration will be identified as occurring at tmax.
Measured: Week 1, Week 4
Peak serum concentration
Serum concentrations after single and multiple doses of RYI-018 will be measured and the highest concentration will be identified as Cmax.
Measured: Week 1, Week 4
Area under the serum concentration versus time curve (AUC)
Serum concentrations after single and multiple doses of RYI-018 will be measured and the AUC will be calculated.
Measured: Week 1, Week 4
Apparent volume of distribution
Serum concentrations after single and multiple doses of RYI-018 will be measured and the apparent volume of distribution, Vz, will be calculated.
Measured: Week 1, Week 4
Immunogenicity as determined by the concentration of serum anti-RYI-018 antibodies.
Serum samples at multiple timepoints will be collected for quantitation of anti-RYI-018 antibodies.
Measured: Days 8, 15, 22, 29, 36, 67
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2017
- Study start28 Aug 2017
- Primary completion24 Aug 2018
- Study completion24 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NAFLDStudies 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
- Randomized, placebo controlled, with 3 sequential cohorts
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bird Rock Bio, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ProSciento, Inc., Perspectum
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03261739
- Sponsor's protocol ID
- BRB-018-001-US
- Status last verified
- Mar 2019
- First submitted
- 3 Aug 2017
- Last updated
- 14 Mar 2019
- 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 14 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Adaptive Design Study for the Assessment of the Safety, Tolerability, and Pharmacokinetics of RYI-018 After Repeat Dosing in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)
- ClinicalTrials.gov ID
- NCT03261739
- Acronym / sponsor ID
- BRB-018-001-US
- Conditions
- NAFLD
- Keywords
- NAFLD, CB1 receptor blockade, anti-CB1 monoclonal antibody
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Bird Rock Bio, Inc.Industry (pharma, biotech, devices)
- Collaborators
- ProSciento, Inc., Perspectum
- Study start
- 28 Aug 2017 (actual)
- Primary completion
- 24 Aug 2018 (actual)
- Study completion
- 24 Aug 2018 (actual)
- First posted
- 25 Aug 2017 (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.
BRB-018-001 is a multicenter, adaptive design, randomized, parallel group study to evaluate the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects with NAFLD.
Detailed description
BRB-018-001 will be conducted as a multicenter, adaptive design, randomized, parallel group study to evaluate the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects with NAFLD. Subjects in each cohort shall be randomized to either RYI-018 or placebo as weekly injection for four weeks. The active doses of RYI-018 will be as follows: Cohort 1: 0.6 mg/kg, Cohort 2: 1.2 mg/kg, and Cohort 3: 2.5 mg/kg. Primary endpoints include safety and tolerability. Secondary endpoints include pharmacokinetics and immunogenicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, placebo controlled, with 3 sequential cohorts
| Arm | Type | Receives |
|---|---|---|
| RYI- 018 | Experimental | Biological: RYI-018The doses of RYI-018 to be evaluated in sequential cohorts will be 0.6 mg/kg, 1.2 mg/kg, and 2.5 mg/kg. |
| Placebo | Placebo comparator | Biological: Placebovehicle control |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adult male or females, 18 to 65 years of age (inclusive) at the time of screening.
- BMI ≥25.0 and ≤40.0 (kg/m2) (inclusive).
- Liver ultrasound (or transient elastography if approved by medical monitor) which qualitatively shows fatty liver or documented history of NAFLD.
- Liver fat percentage by MRI of approximately 10% or greater (MRI to be performed only in subjects with documented NAFLD or fatty liver by ultrasound or transient elastography if approved by medical monitor).
- Type 2 diabetes or prediabetes.
Key exclusion criteria (17 listed)
- Positive serologic testing for HIV, HBsAg, or HCV.
- Have any known malignancy or history of malignancy, except for basal cell or squamous cell skin cancer that has been treated with no evidence of recurrence for at least 3 months prior to Screening.
- Have any underlying physical or psychological medical condition that, in the opinion of the Investigator or sponsor, would make it unlikely that the subject will complete the study or is not in the subject's best interest
- Liver function tests AST or ALT >5 x ULN at screening. One repeat test may be allowed within 7 days at the discretion of the Investigator.
- Total bilirubin > ULN at screening except in patients with a known history of Gilbert's syndrome.
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 |
|---|---|---|
| RYI-018Anti-CB1 monoclonal antibody | Biological | RYI- 018 |
| PlaceboPlacebo | Biological | Placebo |
Primary outcome
Clinical evaluation of adverse events
Time frame: Continuous through 67 days
Subjects will be assessed for adverse events attributable to RYI-018
5 secondary outcomes
Time to peak serum concentration
Time frame: Week 1, Week 4
Peak serum concentration
Time frame: Week 1, Week 4
Area under the serum concentration versus time curve (AUC)
Time frame: Week 1, Week 4
Apparent volume of distribution
Time frame: Week 1, Week 4
Immunogenicity as determined by the concentration of serum anti-RYI-018 antibodies.
Time frame: Days 8, 15, 22, 29, 36, 67
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 14 Mar 2019.
Related trials for NAFLD
Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease
RecruitingPhase 2
A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) Due to MASH
Metabolic Dysfunction-Associated Steatohepatitis, Non-alcoholic Fatty Liver Disease
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.
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RYI-018 in people with NAFLD, run by Bird Rock Bio, Inc. at 6 sites in 3 countries.
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 7 inclusion and 17 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 14 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Australia, Canada. 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?
Clinical evaluation of adverse events (time frame: Continuous through 67 days). 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 14 Mar 2019.