A Study of Safety and Efficacy of HPN-100 in Subjects With Cirrhosis and Episodic Hepatic Encephalopathy (HALT-HE)

Amgen

Status and phase

Completed

Phase 2

Conditions

Hepatic Encephalopathy

Cirrhosis

Treatments

Drug: Placebo

Drug: HPN-100

Study type

Interventional

Funder types

Industry

Identifiers

NCT00999167

HPN-100-008

Details and patient eligibility

About

This is a phase 2 study of HPN-100 in subjects with hepatic encephalopathy (HE) consisting of an open label safety lead-in (Part A), followed by randomized, double-blind, placebo-controlled treatment (Part B).

Full description

Part A: Open-label, dose-escalation lead-in to assess HPN-100 safety and PK Approximately 10 subjects with HE and cirrhosis classified as Child Pugh B or C will undergo a one-step dose escalation over 4 weeks. Subjects will initially receive 6 mL HPN-100 BID for 1 week. On Day 7 and following satisfactory safety assessment of the subject, the dose will be escalated to 9 mL BID for an additional 3 weeks.

In addition to a safety assessment, subjects will undergo 12-hour PK assessments on Days 7 and 28, with sampling at the following time points (relative to the first dose): 0 (pre-first daily dose of HPN-100), 2, 4, 8 (approximately 2 hours before the second daily dose of HPN 100), and 12 hours post-first dose (approximately 2 hours after the second daily dose of HPN-100). Additional PK samples will be collected on Days 8, 15, and 21 (at pre-first dose and 4 hours post-first dose).

The DSMB will review all safety information, including laboratory values, to determine if Part B may be initiated.

Subjects enrolled in Part A may be eligible for Part B as long as they meet the eligibility criteria.

Part B: Randomized, double-blind assessment of HPN-100 in HE subjects Subjects who meet all entry criteria and are judged to be compliant with their prescribed SOC will be eligible for randomization to receive either HPN-100 or matching placebo for 16 weeks. Efficacy will be assessed by the proportion of subjects experiencing episodes of HE, as well as by other outcome measures, including daily home assessments.

Study acquired from Horizon in 2024.

Enrollment

189 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Subjects aged 18 and over
Clinical diagnosis of cirrhosis of any cause
Potential to benefit from HE treatment
History of greater than or equal to 2 documented episodes of WH Grade 2 or more HE within the past 6 months, at least one of which occurred within the preceding 3 months
No change in other HE-specific medications within 1 week before randomization
Able to give informed consent and comply with study activities
Availability of at least one designated family member or caregiver who is capable of and willing to assume responsibility for facilitating subject compliance with study procedures
All females of childbearing age and all sexually active males must agree to use an acceptable method of contraception throughout the study.

Exclusion criteria

Use of any investigational drug within 30 days
Use of prohibited medications
Uncontrolled infection
Active GI bleeding or a history of GI bleeding requiring blood transfusion (> 2 units) within 3 months
Transjugular intrahepatic portosystemic shunt (TIPS) placement or revision within the past 90 days
Recreational drug use or alcohol consumption for subjects with a history of alcohol or drug abuse within 6 months
Lactating and/or pregnant females
Active malignancy
Clinically significant bowel disease, including obstruction, inflammatory bowel disease, or malabsorption
Expected to undergo transplantation within 6 months
Model for end-stage liver disease (MELD) score of > 25