A Study of Mericitabine in Combination With Boceprevir and Pegasys/Copegus in Patients With Chronic Hepatitis C

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01482403

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

2.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized, double-blind, multi-center, placebo-controlled, parallel-group study will evaluate the sustained virologic response and the safety of mericitabine (RO5024048) in combination with boceprevir and Pegasys/Copegus in patients with chronic hepatitis C infection. The anticipated time on study treatment is up to 48 weeks.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: Copegus Drug: Copegus Drug: Pegasys Drug: Pegasys Drug: boceprevir Drug: boceprevir Drug: mericitabine Drug: mericitabine placebo Drug: boceprevir placebo Drug: boceprevir	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

58 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase II, Randomized, Double-Blind, Multicenter, Parallel Group Study to Evaluate the Sustained Virologic Response of the HCV Polymerase Inhibitor Prodrug RO5024048 in Combination With Boceprevir and Pegasys®/Copegus® in Patients With Chronic Hepatitis C Genotype 1 Virus Infection Who Were Prior Null Responders to Treatment With Pegylated Interferon/Ribavirin

Study Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Jan 1, 2014

Actual Study Completion Date :

Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm A 24 weeks of therapy with mericitabine 1000 mg twice a day (BID), boceprevir 800 mg three times daily (TID), Pegasys 180 microgram/week, and Copegus 1000/1200 mg/day (total treatment duration of 24 weeks), followed by a 24-week treatment-free follow-up period.	Drug: Copegus total daily dose of 1000 mg or 1200 mg for 24 weeks Drug: Pegasys 180 microgram subcutaneous once a week for 24 weeks Drug: boceprevir 800 mg three times a day for 24 weeks Drug: mericitabine 1000 mg twice daily for 24 weeks
Experimental: Treatment Arm B 24 weeks of therapy with mericitabine + boceprevir + Pegasys/Copegus followed by 24 weeks of therapy with boceprevir + Pegasys/Copegus (triple) (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.	Drug: Copegus total daily dose of 1000 mg or 1200 mg for 48 weeks Drug: Pegasys 180 microgram subcutaneous once a week for 48 weeks Drug: boceprevir 800 mg three times a day for 48 weeks Drug: mericitabine 1000 mg twice daily for 24 weeks
Active Comparator: Treatment Arm C (Control) 4 weeks of therapy with mericitabine placebo, boceprevir placebo + Pegasys/Copegus, then 20 weeks of therapy with mericitabine placebo + boceprevir + Pegasys/Copegus, then 24 weeks of therapy with boceprevir + Pegasys/Copegus (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.	Drug: Copegus total daily dose of 1000 mg or 1200 mg for 48 weeks Drug: Pegasys 180 microgram subcutaneous once a week for 48 weeks Drug: mericitabine placebo mericitabine placebo Drug: boceprevir placebo boceprevir placebo Drug: boceprevir 800 mg three times a day for 44 weeks

Arm

Intervention/Treatment

Experimental: Treatment Arm A

24 weeks of therapy with mericitabine 1000 mg twice a day (BID), boceprevir 800 mg three times daily (TID), Pegasys 180 microgram/week, and Copegus 1000/1200 mg/day (total treatment duration of 24 weeks), followed by a 24-week treatment-free follow-up period.

Drug: Copegus

total daily dose of 1000 mg or 1200 mg for 24 weeks

Drug: Pegasys

180 microgram subcutaneous once a week for 24 weeks

Drug: boceprevir

800 mg three times a day for 24 weeks

Drug: mericitabine

1000 mg twice daily for 24 weeks

Experimental: Treatment Arm B

24 weeks of therapy with mericitabine + boceprevir + Pegasys/Copegus followed by 24 weeks of therapy with boceprevir + Pegasys/Copegus (triple) (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.

Drug: Copegus

total daily dose of 1000 mg or 1200 mg for 48 weeks

Drug: Pegasys

180 microgram subcutaneous once a week for 48 weeks

Drug: boceprevir

800 mg three times a day for 48 weeks

Drug: mericitabine

1000 mg twice daily for 24 weeks

Active Comparator: Treatment Arm C (Control)

4 weeks of therapy with mericitabine placebo, boceprevir placebo + Pegasys/Copegus, then 20 weeks of therapy with mericitabine placebo + boceprevir + Pegasys/Copegus, then 24 weeks of therapy with boceprevir + Pegasys/Copegus (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period.

Drug: Copegus

total daily dose of 1000 mg or 1200 mg for 48 weeks

Drug: Pegasys

180 microgram subcutaneous once a week for 48 weeks

Drug: mericitabine placebo

mericitabine placebo

Drug: boceprevir placebo

boceprevir placebo

Drug: boceprevir

800 mg three times a day for 44 weeks

Outcome Measures

Primary Outcome Measures

Sustained virological response 12 weeks after treatment (SVR-12) [up to 60 weeks]

Secondary Outcome Measures

Sustained virological response 4 weeks after treatment [up to 52 weeks]
Virologic response over time [60 weeks]
Proportion of patients who develop treatment resistance [60 weeks]
Safety (incidence of adverse events) [60 weeks]
Pharmacokinetics: trough concentration of RO4995855 [Day 1 and Week 8]
Pharmacokinetics: trough concentration of RO5012433 [Day 1 and Week 8]
Pharmacokinetics: trough concentration of boceprevir [Day 1 and Week 8]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients, >/=18 years of age
Chronic hepatitis C infection for at least 6 months duration
Hepatitis C genotype 1a or 1b
Patients must have discontinued prior hepatitis C treatment at least 12 weeks prior to enrollment in this study
Patient showed a previous null response to therapy as defined by < 2 log10 IU/mL decrease in viral titer after at least 12 weeks of treatment with PEG-IFN/RBV

Exclusion Criteria:

Hepatitis C infection with a genotype other than genotype 1a or 1b
Body mass index <18 or >/=36
Hepatitis A, hepatitis B, or HIV infection
Herbal remedies </=1 month prior to the first dose of study drug

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Littleton	Colorado	United States	80120
2	Chicago	Illinois	United States	60637
3	Shreveport	Louisiana	United States	71130
4	Detroit	Michigan	United States	48202
5	Kansas City	Missouri	United States	64128
6	San Antonio	Texas	United States	78215
7	Chesapeake	Virginia	United States	23320-1706
8	Calgary	Alberta	Canada	T2N 4Z6
9	Vancouver	British Columbia	Canada	V5Z 1H2
10	London	Ontario	Canada	N6A 5A5
11	Creteil		France	94010
12	Nice		France	06202
13	Rennes		France	35033
14	Berlin		Germany	13353
15	Hamburg		Germany	20099
16	Hannover		Germany	30625
17	Napoli	Campania	Italy	80131
18	Milano	Lombardia	Italy	20121
19	Firenze	Toscana	Italy	50134
20	Ponce		Puerto Rico	00716
21	Santander	Cantabria	Spain	39008
22	Palma de Mallorca	Islas Baleares	Spain	07010
23	Pontevedra		Spain	36071
24	Valencia		Spain	46014