NCT02105467

Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naïve Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6 (MK-5172-060)

Completed Phase 3 Results posted Last updated 2 October 2018

What this trial tests

Phase 3 trial testing Grazoprevir 100mg / Elbasvir 50 mg FDC in Chronic Hepatitis C Virus in 421 participants. Completed in 6 September 2015.

Timeline

5 June 2014

Primary endpoint
26 February 2015

6 September 2015

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	421
Start date	5 June 2014
Primary completion	26 February 2015
Estimated completion	6 September 2015

Drugs / interventions tested

• Grazoprevir 100mg / Elbasvir 50 mg FDC — full drug profile →
• Placebo to Grazoprevir / Elbasvir 50 mg FDC — full drug profile →

Conditions studied

• Chronic Hepatitis C Virus — all drugs for Chronic Hepatitis C Virus →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Chronic Hepatitis C Virus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks After the End of Treatment (SVR12) Primary · Week 24 (12 weeks after the end of treatment)

Hepatitis C Virus (HCV) ribonucleic acid (RNA) was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR12 was defined as HCV RNA \<Lower Limit of Quantification (\<15 IU/mL) 12 weeks after the end of all study therapy.

Group	Value	95% CI
Immediate Treatment Group	94.6	91.5 – 96.8

Percentage of Participants Experiencing at Least One Adverse Event Primary · Up to Week 14 (14 days after the Blinded Treatment was completed)

An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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 of a preexisting condition that is temporally associated with the use o

Group	Value	95% CI
Immediate Treatment Group	67.4
Deferred Treatment Group	68.6

Percentage of Participants Discontinued From Study Treatment Because of an Adverse Event Primary · Up to Week 12 (end of Blinded Treatment)

An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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 of a preexisting condition that is temporally associated with the use o

Group	Value	95% CI
Immediate Treatment Group	0.9
Deferred Treatment Group	1.0

Percentage of Participants Achieving Sustained Virologic Response at 4 Weeks After the End of Treatment (SVR4) Secondary · Week 16 (4 weeks after the end of treatment)

Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR4 was defined as HCV RNA \<Lower Limit of Quantitation (\<15 IU/mL) 4 weeks after the end of all study therapy.

Group	Value	95% CI
Immediate Treatment Group	97.2	94.7 – 98.7

Percentage of Participants Achieving Sustained Virologic Response at 24 Weeks After the End of Treatment (SVR24) Secondary · Week 36 (24 weeks after the end of treatment)

Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR24 was defined as HCV RNA \<Lower Limit of Quantitation (\<15 IU/mL) 24 weeks after the end of all study therapy.

Group	Value	95% CI
Immediate Treatment Group	94.3	91.1 – 96.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Immediate Treatment Group: Up to Week 36; Deferred Treatment Group (Blinded Treatment): Up to Week 16; Deferred Treatment Group (Open-label Treatment): Week 16 to Week 52. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Immediate Treatment Group

Serious: 15/316 (5%)

Deaths: —

Deferred Treatment Group (Blinded Treatment)

Serious: 4/105 (4%)

Deaths: —

Deferred Treatment Group (Open-label Treatment)

Serious: 3/103 (3%)

Deaths: —

Serious adverse events (24 terms)

Reaction	System	Immediate Treatment Group	Deferred Treatment Group (…	Deferred Treatment Group (…
Myocardial infarction	Cardiac disorders	—	—	—
Ventricular arrhythmia	Cardiac disorders	—	—	—
Meniere's disease	Ear and labyrinth disorders	—	—	—
Retinal haemorrhage	Eye disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Hiatus hernia strangulated	Gastrointestinal disorders	—	—	—
Accidental overdose	Injury, poisoning and procedural complications	—	—	—
Multiple fractures	Injury, poisoning and procedural complications	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—
Renal colic	Renal and urinary disorders	—	—	—
Skin ulcer	Skin and subcutaneous tissue disorders	—	—	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—	—	—
Acute Myocardial Infarction	Cardiac disorders	—	—	—
Pancreatitis acute	Gastrointestinal disorders	—	—	—
Asthenia	General disorders	—	—	—
Chest pain	General disorders	—	—	—
Peritoneal abscess	Infections and infestations	—	—	—
Tooth abscess	Infections and infestations	—	—	—
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	—	—	—
Adenocarcinoma pancreas	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Hypotension	Vascular disorders	—	—	—

Other adverse events (11 terms — click to expand)

Reaction	System	Immediate Treatment Group	Deferred Treatment Group (…	Deferred Treatment Group (…
Headache	Nervous system disorders	—	—	—
Fatigue	General disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—

Most-reported serious reactions: Myocardial infarction, Ventricular arrhythmia, Meniere's disease, Retinal haemorrhage, Abdominal pain upper, Hiatus hernia strangulated, Accidental overdose, Multiple fractures.

Data from ClinicalTrials.gov NCT02105467 adverse events section.

Sponsor's own description

This was an efficacy and safety study of grazoprevir (MK-5172) in combination with elbasvir (MK-8742) in treatment-naive participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infection. Participants were randomly assigned (3:1 ratio) to immediate treatment or deferred treatment (placebo control). The primary efficacy hypothesis was that the proportion of participants receiving combination therapy in the Immediate Treatment Arm who achieve sustained viral response at 12 weeks after the end of study treatment (SVR12) is superior to 73%.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
   Zeuzem S, Ghalib R, Reddy KR, Pockros PJ, et al · · 2015 · cited 403× · PMID 25909356 · DOI 10.7326/m15-0785
2. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis.
   Jacobson IM, Lawitz E, Kwo PY, Hézode C, et al · · 2017 · cited 59× · PMID 28193518 · DOI 10.1053/j.gastro.2017.01.050
3. The safety and efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 1b infection.
   Zeuzem S, Serfaty L, Vierling J, Cheng W, et al · · 2018 · cited 36× · PMID 29344726 · DOI 10.1007/s00535-018-1429-3
4. Changes in liver stiffness measurement using acoustic radiation force impulse elastography after antiviral therapy in patients with chronic hepatitis C.
   Chen SH, Lai HC, Chiang IP, Su WP, et al · · 2018 · cited 13× · PMID 29293628 · DOI 10.1371/journal.pone.0190455
5. A knowledge graph of clinical trials ([Formula: see text]).
   Chen Z, Peng B, Ioannidis VN, Li M, et al · · 2022 · cited 11× · PMID 35304504 · DOI 10.1038/s41598-022-08454-z
6. An integrated analysis of elbasvir/grazoprevir in Korean patients with hepatitis C virus genotype 1b infection.
   Lee YJ, Heo J, Kim DY, Chung WJ, et al · · 2019 · cited 7× · PMID 31132846 · DOI 10.3350/cmh.2019.0006
7. Concomitant proton pump inhibitor use does not reduce the efficacy of elbasvir/grazoprevir: A pooled analysis of 1,322 patients with hepatitis C infection.
   Reau N, Robertson MN, Feng HP, Caro L, et al · · 2017 · cited 5× · PMID 29404492 · DOI 10.1002/hep4.1081
8. Grazoprevir and Elbasvir in Patients with Genotype 1 Hepatitis C Virus Infection: A Comprehensive Efficacy and Safety Analysis.
   Yao Y, Yue M, Wang J, Chen H, et al · · 2017 · cited 4× · PMID 28164081 · DOI 10.1155/2017/8186275