A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of ACH-0137171 in Participants With Chronic Hepatitis C Infection

HCV Infection Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Multiple Doses of ACH-0137171 in Subjects With Chronic Hepatitis C Infection

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00401947
• Other study ID #: ACH171-002
• Status: Terminated
• Phase: Phase 2
• Start date: November 30, 2006
• Est. completion date: March 31, 2007

Study information

• Verified date: September 2022
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to investigate the safety, tolerability, pharmacokinetics (PK), and antiviral activity of multiple doses of ACH-0137171 in participants with chronic hepatitis C virus (HCV) infection.

Description:

This was a randomized, double-blind, placebo-controlled, dose-escalation study of ACH-0137171 in participants with chronic HCV infection.

Sequential cohorts of 10 participants were randomized (8:2) to receive multiple doses of ACH-0137171 or placebo for 4 days (Days 1 through 4) with a single dose on Day 5 followed by a complete PK profile. Dosing was 300-600 milligrams (mg) administered either every 12 hours or every 6 hours (maximum daily dose of 2400 mg). All doses were administered with food.

The dose cohorts were as follows:

Study Schema:

Cohort 1: 300 mg ACH-0137171/placebo every 12 hours (600 mg/day) Cohort 2: 300 mg ACH-0137171/placebo every 6 hours (1200 mg/day) Cohort 3: 600 mg ACH-0137171/placebo every 6 hours (2400 mg/day)

A full review of all safety data will occur following each cohort. Depending on the data, the Sponsor, in consultation with the Principal Investigator(s), may consider modifying the planned dose escalation. The Sponsor may choose to interject an intermediate dose cohort between 2 planned dose escalations or repeat a given dose level, or extend the dosing period, or add an additional cohort. If a similar Grade 3 or 4 adverse event occurs in 3 or more participants and was considered to be at least possibly related to the study drug, escalation to a higher dose will not occur.

Serial HCV ribonucleic acid (RNA) measurements, PK measurements of plasma concentrations of ACH-0137171, and periodic safety monitoring occurred on Days 1 through 5. Additional HCV RNA and PK measurements were taken on Days 6 through 9. Follow-up safety evaluations will be completed 14 days after the last study drug administration (that is, on Days 12 and 19).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: March 31, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Chronic HCV infection must be documented by positive anti-HCV antibody using a third-generation enzyme immunoassay and persistent detection of HCV RNA in the blood for at least 6 months.

• Participants must be infected with HCV genotype 1 (line probe assay; INNO-LiPA HCV II, Innogenetics) and maybe treatment-naïve or treatment-experienced (treatment experienced specifically means prior treatment with interferon, standard or pegylated, with or without ribavirin with therapy stopped > 6 months prior to screening).

• Eligible participants must have had alanine aminotransferase and aspartate aminotransferase < 5 x upper limit of normal (ULN), plasma HCV RNA > 5 log10 international units (IU)/milliliter (mL), and have had no clinical or laboratory evidence of hepatic decompensation for inclusion (must have platelets > 100,000/cubic millimeter [mm^3], total bilirubin < 1.5 x ULN, prothrombin time < 1.5 x ULN, or albumin > 3.0 grams/deciliter [g/dL] for inclusion).

• Women were eligible if not pregnant or breast-feeding.

• Women of childbearing potential (that is, not surgically sterile or confirmed post menopausal) must have had confirmed negative pregnancy tests. All participants must practice a medically acceptable form of contraception.

Exclusion Criteria:

• Human immunodeficiency virus or hepatitis B virus co-infection known cirrhosis.

• Prior history of clinical hepatic decompensation (ascites, jaundice, encephalopathy, or variceal hemorrhage), alcoholic or other forms of chronic liver disease, evidence of hepatocellular carcinoma (a-fetoprotein > 50 nanograms/mL), creatinine clearance < 80 mL/minute (using Cockcroft-Gault equation), hemoglobin < 10 g/dL, neutrophils < 1500/mm^3, and abnormal thyroid function tests (thyroid stimulating hormone > 2.5 microIU/mL, free T4 > ULN), or, a positive test result for illicit drugs, alcohol, or drug abuse within the past 12 months.

• Participants who have had significant gastrointestinal, thyroid, renal, cardiovascular, pulmonary, oncologic, or neurological disease, or who are currently receiving immunomodulators (corticosteroids), investigational, nephrotoxic or hepatotoxic drugs (for example, phenytoin, carbamazepine, isonicotinic acid hydrazide, azole anti-fungal agents such as ketoconazole, and aminoglycoside antibiotics), non-steroidal anti-inflammatory agents, ibuprofen or acetaminophen (on a daily basis) will also be excluded.

Related Conditions & MeSH terms

• Communicable Diseases
• HCV Infection
• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic
• Infections

Intervention

Drug:
• ACH-0137171

Locations

Country	Name	City	State
Germany	Clinical Trial Site	Berlin
Netherlands	Clinical Trial Site	Utrecht
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Dallas	Texas
United States	Clinical Trial Site	La Jolla	California
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Phoenix	Arizona
United States	Clinical Trial Site	San Antonio	Texas
United States	Clinical Trial Site	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals	Achillion, a wholly owned subsidiary of Alexion

Countries where clinical trial is conducted

United States,  Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the short-term safety and tolerability of multiple, escalating, oral doses of ACH-0137171 in subjects with chronic hepatitis C infection.
Primary	To characterize the plasma pharmacokinetics of ACH-0137171 following administration of multiple, escalating, oral doses in subjects with chronic hepatitis C infection.
Primary	To assess the antiviral activity of ACH-0137171 as measured by plasma HCV RNA levels in subjects with chronic hepatitis C infection following administration of multiple, escalating, oral doses.
Primary	To assess the correlation between antiviral activity and pharmacokinetic parameters.
Secondary	To perform viral dynamic and pharmacodynamic modeling of ACH 0137171 virologic response.
Secondary	To assess the biochemical response of ACH-0137171 as measured by the change from baseline of serum ALT and AST levels.