A Study of Combination Treatment With an HCV Polymerase Inhibitor (RO5024048) and an HCV Protease Inhibitor (RO5190591/Danoprevir) in Genotype 1 Chronic Hepatitis C Patients - Full Text View

Purpose

This 7 cohort study will evaluate the efficacy and safety of combination treatment with an HCV nucleoside polymerase inhibitor(RO5024048)and an HCV protease inhibitor(RO5190591/ITMN-191/danoprevir) in patients with chronic hepatitis C, genotype 1.Cohorts A,B,C,D and G will be treatment-naive patients, cohort E will be treatment-experienced excluding null responders, and cohort F will be null responders. Cohorts A and B will evaluate doses of 500mg po bid RO5024048 and 100mg po q8h RO5190591, alone or in combination, for up to 7 or 14 days. Cohort C will evaluate combination treatment with either 1000mg po bid RO5024048 and 100mg q8h RO5190591 or 500mg po bid RO5024048 and 200mg q8h RO5190591 for 14 days. Cohort D will evaluate 1000mg po bid RO5024048 and 200mg q8h RO5190591 for 14 days.Cohort E will evaluate 1000mg RO5024048/600mg RO5190591 po twice daily for 14 days, and Cohorts F and G will evaluate 1000mg RO5024048/900mg RO5190591 po twice daily for 14 days. Cohorts will be tested sequentially or in parallel, if supported by appropriate safety and pharmacokinetic data.Following the last dose of study medication patients have the option of continuing treatment with Standard of care therapies. The anticipated time on study treatment is <3 months, and the target sample size is <100 individuals.

Condition	Intervention	Phase
Hepatitis C, Chronic	Drug: RO5024048 Drug: danoprevir	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Randomized, Placebo-controlled, Dose-ranging Study to Evaluate the Safety, Tolerability and Antiviral Activity of Combination Treatment With an HCV Polymerase Inhibitor (RO5024048) and an HCV Protease Inhibitor (RO5190591) in Genotype 1 Chronic Hepatitis C Patients. INFORM 1

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Proteinase inhibitor

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

HCV RNA [ Time Frame: At each clinic visit, throughout study ] [ Designated as safety issue: No ]
Adverse events, laboratory parameters, vital signs [ Time Frame: At each clinic visit, throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

PK parameters;viral resistance [ Time Frame: At intervals, throughout study ] [ Designated as safety issue: No ]


Enrollment:	88
Study Start Date:	November 2008
Study Completion Date:	March 2010
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort A	Drug: RO5024048 500mg po bid/100mg po q8h for 7 days
Experimental: Cohort B	Drug: danoprevir 500mg po bid/100mg po q8h for 14 days
Experimental: Cohort C	Drug: danoprevir 1000mg po bid/100mg po q8h for 14 days\n500mg po bid/200mg po q8h for 14 days
Experimental: Cohort D	Drug: danoprevir 1000mg po bid/200mg po q8h for 14 days
Experimental: Cohort E	Drug: danoprevir 1000mg/600mg po twice daily for 14 days
Experimental: Cohort F	Drug: danoprevir 1000mg/900mg po twice daily for 14 days
Experimental: Cohort G	Drug: danoprevir 1000mg/900mg po twice daily for 14 days

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

adult patients, 18-65 years of age;
chronic hepatitis C, genotype 1.

Exclusion Criteria:

decompensated liver disease, or impaired liver function;
presence or history of non-hepatitis C chronic liver disease;
HBsAg or HIV infection;
history of cancer within 5 years, other than localized or in situ cancer of the skin.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00801255

Locations


Australia

Adelaide, Australia, SA 5000

Heidelberg, Australia, 3084

Melbourne, Australia, 3181
New Zealand

Christchurch, New Zealand, 8011

Grafton, New Zealand, 1150

Sponsors and Collaborators

Hoffmann-La Roche

Investigators


Study Director:	Clinical Trials	Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gane EJ, Roberts SK, Stedman CA, Angus PW, Ritchie B, Elston R, Ipe D, Morcos PN, Baher L, Najera I, Chu T, Lopatin U, Berrey MM, Bradford W, Laughlin M, Shulman NS, Smith PF. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet. 2010 Oct 30;376(9751):1467-75. doi: 10.1016/S0140-6736(10)61384-0. Epub 2010 Oct 14.


Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00801255 History of Changes
Other Study ID Numbers:	PP22205
Study First Received:	December 2, 2008
Last Updated:	September 1, 2016
Health Authority:	New Zealand: Health Research Council

Additional relevant MeSH terms:


Hepatitis Hepatitis A Hepatitis C Hepatitis, Chronic Hepatitis C, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections	Flaviviridae Infections Protease Inhibitors HIV Protease Inhibitors Lactams Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Anti-Bacterial Agents

ClinicalTrials.gov processed this record on September 27, 2016