Clinical trial NCT02105662: An Efficacy and Safety Study of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in the Treatment of Chronic Hepatitis C Virus in Participants Who Are Co-Infected With Human Immunodeficiency Virus:C-EDGE CO-INFXN (MK-5172-061)
Official title: A Phase III Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen Grazoprevir (GZR) and Elbasvir (EBR) in Treatment-Naïve Subjects With Chronic HCV GT1, GT4, and GT6 Infection Who Are Co-Infected With HIV
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-04-07
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and safety of grazoprevir (MK-5172) 100 mg in combination with elbasvir (MK-8742) 50 mg in the treatment of chronic hepatitis C virus (HCV) in participants who are co-infected with human immunodeficiency virus (HIV). The primary hypothesis is that the percentage of participants who receive grazoprevir + elbasvir and achieve Sustained Virologic Response after 12 weeks of therapy (SVR12) will be greater than 70%.


Eligibility criteria: Inclusion Criteria:

* Documented chronic HCV genotype (GT) 1, GT4, or GT6 infection with no evidence of non-typeable or mixed GT infection (positive for anti-HCV antibody, HCV RNA, or any of the listed GTs at least 6 months prior to screening must be confirmed by screening lab results)
* Treatment naïve for all anti-HCV treatments
* HIV-1 infection documented by laboratory test
* Currently naïve to treatment with any antiretroviral therapy (ART) and have no plans to initiate ART during this study OR on a HIV ART for at least 8 weeks prior to study entry
* Has not experienced any alteration(s) in HIV therapy within 4 weeks of randomization
* Has at least one viable antiretroviral regimen alternative beyond the current regimen in the event of HIV virologic failure or the development of anti-retroviral drug resistance
* Participants of reproductive potential must agree to remain abstinent from heterosexual activity OR use (or have their partner use) acceptable contraception during heterosexual activity while receiving study drug and for 14 days after last dose of study drug.

Exclusion Criteria:

* Evidence of decompensated liver disease manifested by the presence or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs of symptoms of advanced liver disease
* Co-infected with hepatitis B virus
* History of malignancy \<=5 years prior to study start except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or is under evaluation for other active or suspected malignancy
* Taking or planning to take any HIV therapy that includes a ritonavir-boosted or unboosted protease inhibitor, efavirenz or etravirine
* Currently participating or has participated in a study with an investigational compound within 30 days of study start and is not willing to refrain from participating in another study during this study
* Clinically-relevant drug or alcohol abuse within 12 months of study start
* Pregnant, breast feeding, or expecting to conceive or donate eggs from Day 1 of the study throughout treatment and 14 days after the last dose of study medication, or longer if dictated by local regulations
* Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair
* Poor venous access
* History of gastric surgery (e.g., stapling, bypass) or history of malabsorption disorders (e.g., celiac sprue disease)
* Medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during this study
* History of opportunistic infection in the 6 months prior to study start
* Use of HIV drugs other than a dual nucleoside reverse transcriptase inhibitor (NRTI) backbone of tenofovir or abacavir and either emtricitibine or lamivudine PLUS raltegravir (or dolutegravir or rilpivirine)

Primary outcomes:
measure: Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)
timeFrame: 12 weeks after end of all therapy (Study Week 24)
measure: Percentage of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days
timeFrame: Treatment Period plus first 14 follow-up days (up to 14 weeks)
measure: Percentage of Participants Discontinuing Study Therapy Due to AEs During the Treatment Period
timeFrame: Treatment Period (up to 12 weeks)
Secondary outcomes:
measure: Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)
timeFrame: 24 weeks after end of all therapy (Study Week 36)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Rockstroh JK, Nelson M, Katlama C, Lalezari J, Mallolas J, Bloch M, Matthews GV, Saag MS, Zamor PJ, Orkin C, Gress J, Klopfer S, Shaughnessy M, Wahl J, Nguyen BY, Barr E, Platt HL, Robertson MN, Sulkowski M. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV. 2015 Aug;2(8):e319-27. doi: 10.1016/S2352-3018(15)00114-9. Epub 2015 Jul 9.
citation: Asselah T, Reesink H, Gerstoft J, de Ledinghen V, Pockros PJ, Robertson M, Hwang P, Asante-Appiah E, Wahl J, Nguyen BY, Barr E, Talwani R, Serfaty L. Efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 4 infection: A pooled analysis. Liver Int. 2018 Sep;38(9):1583-1591. doi: 10.1111/liv.13727. Epub 2018 Mar 31.
citation: Reau N, Robertson MN, Feng HP, Caro L, Yeh WW, Nguyen BT, Wahl J, Barr E, Hwang P, Klopfer SO. Concomitant proton pump inhibitor use does not reduce the efficacy of elbasvir/grazoprevir: A pooled analysis of 1,322 patients with hepatitis C infection. Hepatol Commun. 2017 Aug 22;1(8):757-764. doi: 10.1002/hep4.1081. eCollection 2017 Oct.
citation: Jacobson IM, Lawitz E, Kwo PY, Hezode C, Peng CY, Howe AYM, Hwang P, Wahl J, Robertson M, Barr E, Haber BA. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis. Gastroenterology. 2017 May;152(6):1372-1382.e2. doi: 10.1053/j.gastro.2017.01.050. Epub 2017 Feb 11.