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)

• ClinicalTrials.gov Identifier: NCT02105662
• Recruitment Status: Completed
• First Posted: April 7, 2014
• Results First Posted: March 4, 2016
• Last Update Posted: February 5, 2021
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Hepatitis C
• Intervention: Drug: Grazoprevir 100 mg/Elbasvir 50 mg fixed-dose combination tablets
• Enrollment: 218

Participant Flow

Recruitment Details
Pre-assignment Details	218 participants were enrolled and treated on study, 212 participants completed 24 weeks of follow-up.

Arm/Group Title	Grazoprevir+Elbasvir
Arm/Group Description	Participants received a fixed-dose combination (FDC) of grazoprevir 100 mg plus elbasvir 50 mg once daily for 12 weeks and were followed-up for 24 weeks.
Period Title: Overall Study
Started	218
Completed	212
Not Completed	6
Reason Not Completed
Lost to Follow-up	5
Withdrawal by Subject	1

Baseline Characteristics

Arm/Group Title		Grazoprevir+Elbasvir
Arm/Group Description		Participants received a FDC of grazoprevir 100 mg plus elbasvir 50 mg once daily for 12 weeks and were followed-up for 24 weeks.
Overall Number of Baseline Participants		218
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	218 participants
		48.7 (8.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	218 participants
	Female	35 16.1%
	Male	183 83.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)
Description	Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 (High Pure System). The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 15 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). SVR12 was defined as undetectable (<9.3 IU/mL) HCV RNA at 12 weeks after the end of all study therapy.
Time Frame	12 weeks after end of all therapy (Study Week 24)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS); all allocated participants who received at least 1 dose of study treatment.

Arm/Group Title	Grazoprevir+Elbasvir
Arm/Group Description:	Participants received a FDC of grazoprevir 100 mg plus elbasvir 50 mg once daily for 12 weeks and were followed-up for 24 weeks.
Overall Number of Participants Analyzed	218
Measure Type: Number; Unit of Measure: percentage of participants
	96.3

2. Primary Outcome

Title	Percentage of Participants Experiencing Adverse Events (AEs) During the Treatment Period and First 14 Follow-up Days
Description	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol -specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time Frame	Treatment Period plus first 14 follow-up days (up to 14 weeks)

Outcome Measure Data

Analysis Population Description

All Participants as Treated (APaT) Population; all participants who received at least one dose of study treatment.

Arm/Group Title	Grazoprevir+Elbasvir
Arm/Group Description:	Participants received a FDC of grazoprevir 100 mg plus elbasvir 50 mg once daily for 12 weeks and were followed-up for 24 weeks.
Overall Number of Participants Analyzed	218
Measure Type: Number; Unit of Measure: percentage of participants
	73.9

3. Primary Outcome

Title	Percentage of Participants Discontinuing Study Therapy Due to AEs During the Treatment Period
Description	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol -specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time Frame	Treatment Period (up to 12 weeks)

Outcome Measure Data

Analysis Population Description

APaT Population; all participants who received at least one dose of study treatment.

Arm/Group Title	Grazoprevir+Elbasvir
Arm/Group Description:	Participants received a FDC of grazoprevir 100 mg plus elbasvir 50 mg once daily for 12 weeks and were followed-up for 24 weeks.
Overall Number of Participants Analyzed	218
Measure Type: Number; Unit of Measure: percentage of participants
	0.0

4. Secondary Outcome

Title	Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)
Description	Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 (High Pure System). The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 15 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). SVR24 was defined as undetectable (<9.3 IU/mL) HCV RNA at 24 weeks after the end of all study therapy.
Time Frame	24 weeks after end of all therapy (Study Week 36)

Outcome Measure Data

Analysis Population Description

FAS; all allocated participants who received at least 1 dose of study treatment.

Arm/Group Title	Grazoprevir+Elbasvir
Arm/Group Description:	Participants received a FDC of grazoprevir 100 mg plus elbasvir 50 mg once daily for 12 weeks and were followed-up for 24 weeks.
Overall Number of Participants Analyzed	218
Measure Type: Number; Unit of Measure: percentage of participants
	93.1

Adverse Events

Time Frame	12 week treatment period plus 24 week follow-up period (up to 36 weeks)
Adverse Event Reporting Description	APaT Population; all participants who received at least one dose of study treatment.
Arm/Group Title	Grazoprevir + Elbasvir
Arm/Group Description	Participants received a FDC of grazoprevir 100 mg plus elbasvir 50 mg once daily for 12 weeks and were followed-up for 24 weeks.
All-Cause Mortality
	Grazoprevir + Elbasvir
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Grazoprevir + Elbasvir
	Affected / at Risk (%)	# Events
Total	8/218 (3.67%)
Infections and infestations
Erysipelas † 1	1/218 (0.46%)	1
Peritonitis bacterial † 1	1/218 (0.46%)	1
Pneumonia † 1	1/218 (0.46%)	1
Cellulitis † 1	1/218 (0.46%)	1
Injury, poisoning and procedural complications
Ulna fracture † 1	1/218 (0.46%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of the tongue † 1	1/218 (0.46%)	1
Nervous system disorders
Seizure † 1	1/218 (0.46%)	1
Psychiatric disorders
Acute psychosis † 1	1/218 (0.46%)	1
Renal and urinary disorders
Urinary retention † 1	1/218 (0.46%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Grazoprevir + Elbasvir
	Affected / at Risk (%)	# Events
Total	106/218 (48.62%)
Gastrointestinal disorders
Abdominal pain upper † 1	11/218 (5.05%)	11
Diarrhoea † 1	18/218 (8.26%)	19
Nausea † 1	20/218 (9.17%)	20
General disorders
Fatigue † 1	29/218 (13.30%)	31
Infections and infestations
Nasopharyngitis † 1	14/218 (6.42%)	14
Upper respiratory tract infection † 1	17/218 (7.80%)	18
Nervous system disorders
Headache † 1	27/218 (12.39%)	33
Psychiatric disorders
Insomnia † 1	16/218 (7.34%)	16
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.

Results Point of Contact

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

Publications:

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. Erratum In: Lancet HIV. 2015 Aug;2(8):e316. Lancet HIV. 2015 Oct;2(10):e416.

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

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.

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.

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.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02105662
• Other Study ID Numbers: 5172-061; 2014-000342-30 ( EudraCT Number )
• First Submitted: April 2, 2014
• First Posted: April 7, 2014
• Results First Submitted: February 3, 2016
• Results First Posted: March 4, 2016
• Last Update Posted: February 5, 2021