HCV InfectionPhase 2NCT00401947
A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of ACH-0137171 in Participants With Chronic Hepatitis C Infection
A Phase 2 study testing ACH-0137171 in people with HCV Infection, run by Alexion Pharmaceuticals, Inc. at 9 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- HCV Infection
- What is being tested?
- ACH-0137171
- How many people
- 30 participants
- Where
- 9 sitesin 3 countries
- Study dates
- 30 Nov 2006to 31 Mar 2007
- Phase
- Phase 2
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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 (α-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.
Trial locations and contacts
9 sites in 3 countries.
9 sites in 3 countries
United States7 sites
Clinical Trial Site
Boston, Massachusetts, 02215
Clinical Trial Site
Dallas, Texas, 75208
Clinical Trial Site
La Jolla, California, 92093
Clinical Trial Site
New York, New York, 10029
Clinical Trial Site
Phoenix, Arizona, 85054
Clinical Trial Site
San Antonio, Texas, 78215
Clinical Trial Site
San Francisco, California, 94143
About this study
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
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.
Read the detailed 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).
- Conditions
- HCV Infection
- Being tested
- ACH-0137171
- Keywords
- HCV, Chronic, Hepatitis
- Medical subject headings
- Hepatitis C, Bronchiolitis Obliterans Syndrome, Hepatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACH-0137171Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the short-term safety and tolerability of multiple, escalating, oral doses of ACH-0137171 in subjects with chronic hepatitis C infection.
To characterize the plasma pharmacokinetics of ACH-0137171 following administration of multiple, escalating, oral doses in subjects with chronic hepatitis C infection.
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.
To assess the correlation between antiviral activity and pharmacokinetic parameters.
Secondary outcomes (2)
To perform viral dynamic and pharmacodynamic modeling of ACH 0137171 virologic response.
To assess the biochemical response of ACH-0137171 as measured by the change from baseline of serum ALT and AST levels.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2006 (estimated)
- Study start30 Nov 2006
- Study completion31 Mar 2007
Why it stopped: Nephrotoxicity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HCV InfectionStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Achillion, a wholly owned subsidiary of Alexion
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00401947
- Sponsor's protocol ID
- ACH171-002
- Status last verified
- Sep 2022
- First submitted
- 17 Nov 2006
- Last updated
- 15 Sep 2022
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00401947
- Acronym / sponsor ID
- ACH171-002
- Conditions
- HCV Infection
- Keywords
- HCV, Chronic, Hepatitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Nephrotoxicity
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Achillion, a wholly owned subsidiary of Alexion
- Study start
- 30 Nov 2006 (actual)
- Study completion
- 31 Mar 2007 (actual)
- First posted
- 22 Nov 2006 (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 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.
Detailed 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (3 listed)
- 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 (α-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.
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 |
|---|---|---|
| ACH-0137171 | Drug | – |
Primary outcome
To assess the short-term safety and tolerability of multiple, escalating, oral doses of ACH-0137171 in subjects with chronic hepatitis C infection.
To characterize the plasma pharmacokinetics of ACH-0137171 following administration of multiple, escalating, oral doses in subjects with chronic hepatitis C infection.
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.
To assess the correlation between antiviral activity and pharmacokinetic parameters.
2 secondary outcomes
To perform viral dynamic and pharmacodynamic modeling of ACH 0137171 virologic response.
To assess the biochemical response of ACH-0137171 as measured by the change from baseline of serum ALT and AST levels.
Results and safety
The study was stopped early (reason given: Nephrotoxicity). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2022.
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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.
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ACH-0137171 in people with HCV Infection, run by Alexion Pharmaceuticals, Inc. at 9 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 5 inclusion and 3 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: stopped early, as of the sponsor's last update on 15 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Germany, Netherlands. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: Nephrotoxicity). Results are not available in the source record.
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?
To assess the short-term safety and tolerability of multiple, escalating, oral doses of ACH-0137171 in subjects with chronic hepatitis C infection.. The study lists 4 primary outcomes in all. 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 15 Sep 2022.