Trial Outcomes & Findings for Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination for Chronic Hepatitis C Virus (HCV) Genotypes 1, 4, and 6 (MK-5172-065) (NCT NCT02252016)

NCT ID: NCT02252016

Last Updated: 2018-10-03

Results Overview

The percentage of participants in the both arms achieving SVR12 (i.e., HCV riboncleic acid \[RNA\] level below the lower limit of quantification \[LLoQ\] 12 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of \<15 IU/mL.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

159 participants

Primary outcome timeframe

12 weeks after completing study therapy (Week 24)

Results posted on

2018-10-03

Participant Flow

Adult participants with hepatitis C virus (HCV) genotypes (GT)1, GT4, and GT6 with inherited blood disorders and with or without human immunodeficiency virus (HIV) co-infection were recruited at study centers around the world.

Participant milestones

Participant milestones
Measure	Immediate Treatment Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.	Deferred Treatment Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Overall Study STARTED	107	52
Overall Study COMPLETED	104	49
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Immediate Treatment Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.	Deferred Treatment Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Overall Study Lost to Follow-up	2	1
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination for Chronic Hepatitis C Virus (HCV) Genotypes 1, 4, and 6 (MK-5172-065)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Immediate Treatment n=107 Participants Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.	Deferred Treatment n=52 Participants Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.	Total n=159 Participants Total of all reporting groups
Age, Continuous	44.2 Years STANDARD_DEVIATION 11.2 • n=5 Participants	42.5 Years STANDARD_DEVIATION 9.8 • n=7 Participants	43.6 Years STANDARD_DEVIATION 10.7 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	13 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	80 Participants n=5 Participants	39 Participants n=7 Participants	119 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks after completing study therapy (Week 24)

Population: The Full Analysis Set (FAS) consists of all treated participants in both arms other than those who discontinued with reasons unrelated to the treatment regimen or HCV response.

Outcome measures

Outcome measures
Measure	Immediate Treatment n=107 Participants Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.	Deferred Treatment n=49 Participants Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)	93.5 Percentage of participants Interval 87.0 to 97.3	91.8 Percentage of participants Interval 80.4 to 97.7

PRIMARY outcome

Timeframe: Up to Week 14

Population: The All-Participants-as-Treated (APaT) population includes all participants receiving ≥1 dose(s) of study drug. For the Deferred Treatment arm, data indicate results obtained during the initial 12-week placebo treatment period.

An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Immediate Treatment n=107 Participants Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.	Deferred Treatment n=52 Participants Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Percentage of Participants Experiencing an Adverse Event (AE)	72.9 Percentage of Participants	65.4 Percentage of Participants

PRIMARY outcome

Timeframe: Up to Week 12

Population: The APaT population includes all participants receiving ≥1 dose(s) of study drug. For the Deferred Treatment arm, data indicate results obtained during the initial 12-week placebo treatment period.

An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Immediate Treatment n=107 Participants Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.	Deferred Treatment n=52 Participants Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Percentage of Participants Discontinuing From Study Treatment Due to an AE(s)	0.0 Percentage of Participants	1.9 Percentage of Participants

SECONDARY outcome

Timeframe: 24 weeks after completing study therapy (Week 36)

Population: The FAS consists of all treated participants in both arms other than those who discontinued with reasons unrelated to the treatment regimen or HCV response.

The percentage of participants in both arms achieving SVR24 (i.e., HCV RNA level below the LLoQ 24 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of \<15 IU/mL.

Outcome measures

Outcome measures
Measure	Immediate Treatment n=107 Participants Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.	Deferred Treatment n=49 Participants Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)	90.7 Percentage of participants Interval 83.5 to 95.4	91.8 Percentage of participants Interval 80.4 to 97.7

Adverse Events

Immediate Treatment

Serious events: 6 serious events

Other events: 78 other events

Deaths: 0 deaths

Deferred Treatment: Placebo Phase

Serious events: 6 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Immediate Treatment n=107 participants at risk Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.	Deferred Treatment: Placebo Phase n=52 participants at risk Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Gastrointestinal disorders Abdominal distension	1.9% 2/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	5.8% 3/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Gastrointestinal disorders Abdominal pain	6.5% 7/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	3.8% 2/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Gastrointestinal disorders Diarrhoea	3.7% 4/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	5.8% 3/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Gastrointestinal disorders Nausea	8.4% 9/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	15.4% 8/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
General disorders Asthenia	7.5% 8/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	3.8% 2/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
General disorders Fatigue	16.8% 18/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	7.7% 4/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
General disorders Pyrexia	5.6% 6/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	0.00% 0/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Infections and infestations Nasopharyngitis	5.6% 6/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	3.8% 2/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	6.5% 7/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	5.8% 3/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Haemarthrosis	2.8% 3/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	7.7% 4/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.93% 1/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	7.7% 4/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Nervous system disorders Headache	21.5% 23/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	11.5% 6/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.

Additional Information

Senior Vice President, Glocal Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Immediate Treatment n=107 participants at risk Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.	Deferred Treatment: Placebo Phase n=52 participants at risk Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.
Blood and lymphatic system disorders Anaemia	0.00% 0/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	1.9% 1/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Blood and lymphatic system disorders Sickle cell anaemia with crisis	0.93% 1/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	3.8% 2/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Cardiac disorders Myocardial infarction	0.93% 1/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	0.00% 0/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Cardiac disorders Sinus bradycardia	0.93% 1/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	0.00% 0/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Gastrointestinal disorders Gastritis erosive	0.93% 1/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	0.00% 0/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Gastrointestinal disorders Rectal haemorrhage	0.93% 1/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	0.00% 0/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Hepatobiliary disorders Hepatitis acute	0.93% 1/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	0.00% 0/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Infections and infestations Gastroenteritis	0.93% 1/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	0.00% 0/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Injury, poisoning and procedural complications Fall	0.00% 0/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	1.9% 1/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Investigations Alanine aminotransferase increased	0.00% 0/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	1.9% 1/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Investigations Aspartate aminotransferase increased	0.00% 0/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	1.9% 1/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Metabolism and nutrition disorders Hypophosphataemia	0.93% 1/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	0.00% 0/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	1.9% 1/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	1.9% 1/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Periarthritis	0.93% 1/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	0.00% 0/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.00% 0/107 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.	1.9% 1/52 • Up to 52 weeks An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.