Safety, Tolerability and Efficacy of 12-weeks of Sovaprevir, ACH-3102 and Ribavirin in Treatment-naive GT-1 HCV Subjects

• ClinicalTrials.gov Identifier: NCT01849562
• Recruitment Status: Completed
• First Posted: May 8, 2013
• Results First Posted: February 4, 2015
• Last Update Posted: September 17, 2015
• Sponsor: Alexion Pharmaceuticals
• Information provided by (Responsible Party): Alexion Pharmaceuticals

Study Description

Brief Summary:

The purpose of this study is to evaluate the safety, tolerability and efficacy of 12 weeks of treatment with sovaprevir, ACH-0143102 and ribavirin in GT1, treatment-naive, HCV subjects.

Condition or disease	Intervention/treatment	Phase
Hepatitis C, Chronic	Drug: Sovaprevir; Drug: ACH-3102; Drug: RBV; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2a Trial to Evaluate the Safety, Tolerability and Efficacy of 12 Weeks of Sovaprevir, ACH-0143102 and Ribavirin in Treatment-Naive Subjects With Chronic Hepatitis C Genotype-1 Viral Infection
• Study Start Date: April 2013
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: April 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Sovaprevir 200 mg, ACH-3102 150/50 mg, RBV 1000-1200mg; Sovaprevir 200 mg QD + ACH-3102 150 mg loading dose on Day 1 followed by 50 mg QD + RBV weight-based 1000-1200mg QD for 12 weeks	Drug: Sovaprevir; NS3/4A protease inhibitor; Other Name: ACH-0141625; Drug: ACH-3102; NS5A inhibitor; Drug: RBV; Other Name: Ribavirin
Active Comparator: Sovaprevir 400 mg, ACH-3102 150/50mg,RBV1000-1200mg; Sovaprevir 400 mg QD + ACH-3102 150 mg loading dose on Day 1 followed by 50 mg QD + RBV weight-based 1000-1200mg QD for 12 weeks	Drug: Sovaprevir; NS3/4A protease inhibitor; Other Name: ACH-0141625; Drug: ACH-3102; NS5A inhibitor; Drug: RBV; Other Name: Ribavirin
Placebo Comparator: Placebo; Placebo for Sovaprevir capsule QD + placebo for ACH-3102 150 mg loading dose on Day 1 followed by 50 mg capsule QD + placebo for weight-based RBV QD for 12 weeks	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Incidence of Sustained Virologic Response 4 Weeks (SVR4) After the Completion of Treatment. [ Time Frame: Four weeks after the completion of treatment ]
   Incidence of SVR4 after the completion of dosing, reported as HCV RNA less than the lower limit of quantification (<LLOQ), in subjects who received active treatment (sovaprevir and ACH-0143102 in combination with ribavirin) as compared to those who received placebo.
2. Safety and Tolerability of 12 Weeks of Sovaprevir and 3102 in Combination With Ribavirin in Subjects With Chronic Hepatitis C Genotype 1 Viral Infection. [ Time Frame: 12 weeks ]
   To determine safety and tolerability of 12 weeks of sovaprevir/ACH-0143102/RBV in subjects with chronic hepatitis C genotype 1, the following criteria will be used: the number of subjects with discontinuations due to AEs, treatment emergent G3/G4 AEs, treatment emergent G3/G4 laboratory abnormalities, clinically significant ECGs.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Males and Females between ages 18 and 65
• Chronic HCV infection
• HCV genotype 1
• HCV RNA > 10,000 IU/mL at screening.
• Female patients must be willing to use two effective methods of contraception, one of which must be barrier method, during dosing period and six months after last dose of ribavirin. Females of childbearing potential must have a negative pregnancy test at screening and baseline.
• Male patients must be willing to use an effective barrier method of contraception throughout the dosing period and for six months.
• Signed and dated written informed consent form.
• Willing to participate in all study activities and all study requirements (including effective contraception) during study period.
• Treatment naïve subjects defined as subjects who have never received pegylated interferon, RBV, or a direct-acting anti-viral agent for the treatment of chronic HCV infection.
• A liver biopsy within the last 3 years without evidence of cirrhosis.

Exclusion Criteria:

• Body Mass Index (BMI) > 36.0
• Pregnant or nursing (lactating) females, confirmed by a positive human chorionic gonadotropin (HCG) laboratory test or females contemplating pregnancy
• Participation in any interventional clinical trial within 35 days prior to first study medication dose administration on Day 1
• Known HIV-1 or HIV-2 infection/serology and/or positive Hepatitis B Surface Antigen (HBsAg)
• Use of dietary supplements, grapefruit juice, herbal supplements, CYP2C8 substrates, CYP3A4 inducers and inhibitors, PGP inducers and substrates, OATP inhibitors and substrates, and potent inducers of other CYP enzymes within 14 days prior to dosing through 7 days following completion of study meds.
• Clinically significant laboratory abnormality at screening (specified in protocol)
• Other forms of liver disease
• History of severe or uncontrolled psychiatric disease
• History of malignancy of any organ system, treated or untreated within the past 5 years
• History of major organ transplantation
• Use of bone marrow colony stimulating factor agents within 3 months prior to baseline.
• History of seizure disorder requiring ongoing medical therapy
• History of known coagulopathy including hemophilia
• History of hemoglobinopathy, including sickle cell anemia and thalassemia.
• History of immunologically mediated disease (specified in protocol)
• History of clinical evidence of significant chronic cardiac disease ( specified in protocol)
• ECG with any clinically significant abnormality.
• Structural or functional cardiac abnormalities (specified in protocol)
• History of COPD, emphysema, or other chronic lung disease.
• Subjects currently abusing amphetamines, cocaine or opiates, or with ongoing alcohol abuse in the judgement of the investigator

Contacts and Locations

Locations

United States, California

Franco Felizarta

Bakersfield, California, United States, 93301

eStudy Site

La Mesa, California, United States, 91942

United States, Georgia

Gastrointestinal Specialists of Georgia

Marietta, Georgia, United States, 30060

United States, Tennessee

Nashville Gastrointestinal Specialists

Nashville, Tennessee, United States, 78215

United States, Texas

Liver Associates of Texas PA

Houston, Texas, United States, 77030

American Research Corporation

San Antonio, Texas, United States, 78215

United States, Virginia

Medical Associates of Central Virginia

Lynchburg, Virginia, United States, 24501

Canada, Ontario

Toronto Liver Centre

Toronto, Ontario, Canada, M6H3M1

Sponsors and Collaborators

Alexion Pharmaceuticals

More Information

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01849562
• Other Study ID Numbers: ACH102-007
• First Posted: May 8, 2013
• Results First Posted: February 4, 2015
• Last Update Posted: September 17, 2015
• Last Verified: September 2015

Keywords provided by Alexion Pharmaceuticals:

Hepatitis C, Chronic; Genotype 1; Hepatitis C; Liver Diseases; Hepatitis, viral, human; ribavirin; antiviral agents; anti-infective agents; protease inhibitors; NS5a inhibitors

Additional relevant MeSH terms:

Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; Flaviviridae Infections; Hepatitis, Chronic; Ribavirin; Odalasvir; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents