ANNAPURNA: A Study of The Combination of RO5466731, RO5190591, Ritonavir and Copegus (Ribavirin) With or Without RO5024048 in Patients With Chronic Hepatitis C Who Are Either Treatment-Naïve or Have Previously Experienced a Null Response to Interferon-Based Treatment

Hepatitis C, Chronic Clinical Trial

Official title:

Randomized, Open-Label, Multicenter Study of Safety, Efficacy, and Tolerability of the Combination of RO5466731, RO5190591, Ritonavir, and Copegus With or Without RO5024048 in HCV Genotype 1 Infected Patients Who Are Either Treatment Naïve or Null Responders to Previous Interferon-Based Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01628094
• Other study ID #: NP28266
• Secondary ID: 2012-000638-21
• Status: Completed
• Phase: Phase 2
• First received: June 22, 2012
• Last updated: November 1, 2016
• Start date: June 2012
• Est. completion date: November 2013

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This randomized, open-label, multicenter study will evaluate the safety , efficacy and tolerability of the combination treatment RO5466731, RO5190591, ritonavir and Copegus (ribavirin) with or without RO5024048 in patients with chronic hepatitis C genotype 1. In Part 1, treatment-naïve patients will be randomized to receive treatment with RO5466731, RO5190591 plus ritonavir, and Copegus, with or without RO5024048. In Part 2, further treatment-naïve patients will receive a successful regimen from Part 1, or a reduced intensity regimen, and patients who have previously experienced null response to interferon-based treatment will be added to the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients, >/= 18 years of age

• Chronic hepatitis C genotype 1 of >/= 6 months duration at screening

• Part 1 and Part 2: Naïve to treatment with interferon (pegylated or non-pegylated). Patients who have participated in studies investigating a direct-acting antiviral agent with or without interferon are excluded

• Part 2: Treatment experienced patients having a previous null response to treatment with interferon containing regimen

• Liver biopsy or non-invasive (e.g. Fibroscan) evaluation in the past 24 calendar months showing absence of cirrhosis or incomplete/transition to cirrhosis

• Body mass index (BMI) 18 to 35 kg/m2 inclusive and body weight >/= 45 kg

Exclusion Criteria:

• Pregnant or lactating women or males with female partners who are pregnant or lactating

• Decompensated liver disease or impaired liver function (as defined by protocol)

• Cirrhosis or incomplete/transition to cirrhosis

• Non- hepatitis C chronic liver disease

• Positive for hepatitis B or HIV infection

• History of pre-existing renal disease

• History of severe cardiac disease

• History of neoplastic disease within the last 5 years, except for localized or in situ carcinoma of the skin

• History of drug abuse within the last year; history of cannabinoid use is not excluded

• Evidence of alcohol abuse within 1 year of screening and consumption of more than 2 units of alcohol per day

• Medical condition that requires use of systemic corticosteroids

• Received warfarin or other anticoagulants during the 21 days immediately prior to screening or is expected to require warfarin or other anticoagulants during the study

• Anticipated use or need for significant medical treatment during the study or use of concomitant medications or nutrients that are excluded by protocol (e.g. drugs that are contraindicated with ritonavir, hormonal methods of contraception)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• RO5024048

• RO5190591

• RO5466731

• ribavirin [Copegus]

• ritonavir

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Germany,  New Zealand,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virological response (defined as undetectable serum HCV RNA) 12 weeks after end of treatment		approximately 20 months	No
Primary	Safety: Incidence of adverse events		approximately 20 months	No
Secondary	Antiviral activity: Change in serum HCV RNA levels		from baseline to 24 weeks after end of treatment	No
Secondary	Pharmacokinetics in coadministration: Area under the concentration-time curve (AUC)		Pre-dose Weeks 1, 2, 3, 4, 6, 10, and 12 and up to 12 hours post-dose Weeks 1, and 4 or 3 and 6	No
Secondary	HCV drug resistance		approximately 20 months	No
Secondary	Quality of life: Short-Form 36v2/Brief Fatigue Inventory questionnaires		approximately 20 months	No