Moderate to Extensive Hepatic Fibrosis (METAVIR F3-4)Phase 1NCT02227459
Phase 1b/2, Open Label, Repeat Dose, Dose Escalation Study of ND-L02-s0201 Injection in Subjects With Moderate to Extensive Fibrosis (METAVIR F3-4)
A Phase 1 study testing ND-L02-s0201 Injection in people with Moderate to Extensive Hepatic Fibrosis (METAVIR F3-4), run by Bristol-Myers Squibb at 2 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of multiple doses of ND-L02-s0201 in subjects with moderate to extensive hepatic fibrosis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Moderate to Extensive Hepatic Fibrosis (METAVIR F3-4)
- What is being tested?
- ND-L02-s0201 Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Oct 2014to May 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female between 18 and 75 years
- Diagnosis of METAVIR F3-4 hepatic fibrosis determined by liver biopsy done within 12 months before screening (Cohort 1) or at the pre-dose biopsy within 6 weeks before treatment (Cohorts 2 and 3)
- Adequate and stable synthetic hepatic function (albumin ≥ 3 g/dL, international normalized ratio [INR] ≤ 1.4 x upper limit of normal [ULN] and stable by prior medical history).
- Adequate and stable hepatic function as measured by alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamate transferase (GGTP), and total bilirubin (ALT/AST ≤ 5 x ULN, ALP ≤ 4 x ULN, GGTP ≤ 4 x ULN, bilirubin ≤ 2x ULN and stable by prior medical history).
- Platelet count ≥ 75,000/mm3, hemoglobin ≥ 10 g/dL, and white blood cell count (WBC) > 3000/µL.
- No signs of decompensated liver disease (ascites, hepatic encephalopathy, or variceal bleeding).
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- No clinically significant abnormalities on 12-lead electrocardiogram (ECG).
- No other intercurrent medical conditions or infections considered clinically significant by the Investigator.
- Clinical laboratory assessments are within the laboratory limits of normal values or not considered clinically significant by the Investigator.
- Vitamin A levels at screening must be less than or equal to the upper limit of normal (ULN 95 µg/dL or 3.32 µmol/L).
- Any male subject, if sexually active, agrees to use barrier contraceptive techniques as defined in the protocol. If female, the subject must be of non-childbearing potential as defined in the protocol.
- Subjects who are active substances abusers may be enrolled at the discretion of the Principal Investigator.
- Willing and able to provide written informed consent and comply with the study procedures and visit schedule, including follow up visits.
Who cannot join
- Any disease or condition which, in the opinion of the Investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, skeletal, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of ND L02 s0201, or would place the subject at increased risk.
- On ongoing therapy for HCV/HBV, or received therapy for HCV/HBV within 12 weeks prior to administration of study drug.
- On interferon therapy for any disease or received interferon therapy for any disease within 12 weeks prior to administration of study drug.
- History of bone disease, including osteoporosis and osteomalacia, Paget's disease of bone, or a history of unexplained fractures or fractures after minimal trauma.
- Alpha-fetoprotein (AFP) ≥ 50 ng/mL or signs of abnormality or hepatocellular carcinoma on ultrasound survey of the liver.
- Carcinoembryonic antigen (CEA) levels above the ULN.
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- Laboratory test results include abnormal values considered to be clinically significant by the Investigator.
- Participated in a concurrent interventional study with the last intervention occurring within 12 weeks prior to administration of study drug.
- Taken vitamin A or vitamin D supplements or multi-vitamins that contain vitamin A or vitamin D between the screening visit and administration of study drug.
- History, within the last 2 years, of alcohol abuse, significant mental illness, or physical dependence on any opioid.
- Veins unsuitable for repeated venipuncture or IV infusion (eg, veins that are difficult to locate, access or puncture; veins with a tendency to rupture during or after puncture).
- Received recent treatment with alternative therapies, which, in the opinion of the Investigator, could potentially confound clinical or laboratory assessments.
- Lost more than 500 mL of blood within 56 days prior to administration of study drug.
- Body mass index (BMI) > 38 kg/m2.
- History of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness (AIDS).
- History of malignancy within the last 5 years with the exception of basal cell carcinoma.
- Woman of childbearing potential.
- History of hypersensitivity to H2-receptor antagonists.
- Any other reason that, in the opinion of the Investigator or the Sponsor's Medical Monitor, makes the subject unsuitable for enrollment.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Phase 1b/2, Open Label, Randomized, Repeat Dose, Dose Escalation Study to Evaluate the Safety, Tolerability, Biological Activity, and Pharmacokinetics of ND-L02-s0201 Injection, A Vitamin A-coupled Lipid Nanoparticle Containing siRNA Against HSP47, in Subjects With Moderate to Extensive Hepatic Fibrosis (METAVIR F3-4)
The purpose of this study is to evaluate the safety and tolerability of multiple doses of ND-L02-s0201 in subjects with moderate to extensive hepatic fibrosis.
- Being tested
- ND-L02-s0201 Injection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ND-L02-s0201 InjectionDrug
Also called BMS-986263
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Arm A | Experimental | Once a week dosing Receives: Drug: ND-L02-s0201 Injection |
| Experimental: Arm B | Experimental | Twice a week dosing Receives: Drug: ND-L02-s0201 Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with serious and non-serious adverse events
Measured: After treatment for 5 consecutive weeks and follow-up through week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2014 (estimated)
- Study startOct 2014
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Moderate to Extensive Hepatic Fibrosis (METAVIR F3-4)Studies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- 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
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Nitto Denko Corporation
- Responsible party
- Sponsor
- Investigators
- Eric Lawitz, MD, Principal investigator, Texas Liver InstituteRozalina Balabanska, MD, Principal investigator, Tokuda Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02227459
- Sponsor's protocol ID
- ND-L02-s0201-002
- Status last verified
- May 2017
- First submitted
- 25 Aug 2014
- Last updated
- 11 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2, Open Label, Randomized, Repeat Dose, Dose Escalation Study to Evaluate the Safety, Tolerability, Biological Activity, and Pharmacokinetics of ND-L02-s0201 Injection, A Vitamin A-coupled Lipid Nanoparticle Containing siRNA Against HSP47, in Subjects With Moderate to Extensive Hepatic Fibrosis (METAVIR F3-4)
- ClinicalTrials.gov ID
- NCT02227459
- Acronym / sponsor ID
- ND-L02-s0201-002
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Collaborators
- Nitto Denko Corporation
- Study start
- Oct 2014
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 28 Aug 2014 (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.
The purpose of this study is to evaluate the safety and tolerability of multiple doses of ND-L02-s0201 in subjects with moderate to extensive hepatic fibrosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental: Arm A | Experimental | Drug: ND-L02-s0201 InjectionOnce a week dosing |
| Experimental: Arm B | Experimental | Drug: ND-L02-s0201 InjectionTwice a week dosing |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male or female between 18 and 75 years
- Diagnosis of METAVIR F3-4 hepatic fibrosis determined by liver biopsy done within 12 months before screening (Cohort 1) or at the pre-dose biopsy within 6 weeks before treatment (Cohorts 2 and 3)
- Adequate and stable synthetic hepatic function (albumin ≥ 3 g/dL, international normalized ratio [INR] ≤ 1.4 x upper limit of normal [ULN] and stable by prior medical history).
- Adequate and stable hepatic function as measured by alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamate transferase (GGTP), and total bilirubin (ALT/AST ≤ 5 x ULN, ALP ≤ 4 x ULN, GGTP ≤ 4 x ULN, bilirubin ≤ 2x ULN and stable by prior medical history).
- Platelet count ≥ 75,000/mm3, hemoglobin ≥ 10 g/dL, and white blood cell count (WBC) > 3000/µL.
Key exclusion criteria (19 listed)
- Any disease or condition which, in the opinion of the Investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, skeletal, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of ND L02 s0201, or would place the subject at increased risk.
- On ongoing therapy for HCV/HBV, or received therapy for HCV/HBV within 12 weeks prior to administration of study drug.
- On interferon therapy for any disease or received interferon therapy for any disease within 12 weeks prior to administration of study drug.
- History of bone disease, including osteoporosis and osteomalacia, Paget's disease of bone, or a history of unexplained fractures or fractures after minimal trauma.
- Alpha-fetoprotein (AFP) ≥ 50 ng/mL or signs of abnormality or hepatocellular carcinoma on ultrasound survey of the liver.
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 |
|---|---|---|
| ND-L02-s0201 InjectionAlso: BMS-986263 | Drug | Experimental: Arm A, Experimental: Arm B |
Primary outcome
Number of participants with serious and non-serious adverse events
Time frame: After treatment for 5 consecutive weeks and follow-up through week 24
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 11 May 2017.
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.
Eric Lawitz, MD principal investigator
Texas Liver Institute
Rozalina Balabanska, MD principal investigator
Tokuda Hospital
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ND-L02-s0201 Injection in people with Moderate to Extensive Hepatic Fibrosis (METAVIR F3-4), run by Bristol-Myers Squibb at 2 sites in 2 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 13 inclusion and 19 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 11 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Bulgaria. 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. 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?
Number of participants with serious and non-serious adverse events (time frame: After treatment for 5 consecutive weeks and follow-up through week 24). 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 11 May 2017.