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)

NCT02227459 | Completed Phase 1 DMC

• 1 other identifier: ND-L02-s0201-002
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Moderate to Extensive Hepatic Fibrosis (METAVIR F3-4)

Outcome Measures

Primary Outcomes (1)

• Number of participants with serious and non-serious adverse events

  After treatment for 5 consecutive weeks and follow-up through week 24

Study Arms (2)

Experimental: Arm A

EXPERIMENTAL

Once a week dosing

Drug: ND-L02-s0201 Injection

Experimental: Arm B

EXPERIMENTAL

Twice a week dosing

Drug: ND-L02-s0201 Injection

Interventions

ND-L02-s0201 Injection DRUG

Also known as: BMS-986263

Experimental: Arm A; Experimental: Arm B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Nitto Denko Corporation: collaborator

Study Sites (2)

Texas Liver Institute

Austin, Texas, 78215, United States

Location

Tokuda Hospital

Sofia, Bulgaria

Location

Study Officials

• Eric Lawitz, MD

  Texas Liver Institute

  PRINCIPAL INVESTIGATOR

• Rozalina Balabanska, MD

  Tokuda Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2014
• First Posted: August 28, 2014
• Study Start: October 1, 2014
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: May 11, 2017

Record last verified: 2017-05

Locations

US (1); BU (1)