Study of Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Rib... | NCT02105454

ID	Type	Description	Link
2013-004213-41	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
GZR 100 mg + EBR 50 mg + RBV for 12 weeks	Experimental	Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks	Drug: Grazoprevir (GZR) Drug: Elbasvir (EBR) Drug: Ribavirin (RBV)

Name	Type	Description	Arm Group Labels	Other Names
Grazoprevir (GZR)	Drug	100 mg oral tablet (total daily dose)	GZR 100 mg + EBR 50 mg + RBV for 12 weeks

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12)	SVR12 is defined as participants having hepatitis C virus ribonucleic acid (HCV RNA) level lower than the limit of quantification (LLoQ, <15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy.	Up to 24 weeks
Percentage of Participants Experiencing Adverse Events	Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.	Up to 40 weeks (from Day 1 [post-dose] through 24 [-12/+4] weeks following last dose of study drug)
Percentage of Participants Discontinuing Study Drug Due to an Adverse Event	Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.	Up to 12 weeks

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy	SVR12 is defined as participants having HCV RNA level lower than the LLoQ (<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy. Prior DAA therapy regimen included boceprevir, telaprevir, simeprevir, or sofosbuvir taken concomitantly with peginterferon and ribavirin. Below categories specify with our without resistance-associated variants (RAVs) of the hepatitis C virus.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Documented chronic HCV GT1 infection (with no evidence of non-typable or mixed genotype)
Absence of cirrhosis, or cirrhosis with these criteria: METAVIR F4, or Fibroscan with result >12.5 kPa, or FibroSure® (Fibrotest®) score of >0.75 + aspartate aminotransferase (AST): platelet ratio index (APRI) of >2- Prior regimen containing an approved DAA (boceprevir, telaprevir, simeprevir, or sofosbuvir), pegylated interferon, and/or RBV
Participants of reproductive potential must agree to remain truly abstinent or use (or have their partner use) 2 acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations

Exclusion criteria:

Received any HCV regimen containing a DAA with the exception of boceprevir, telaprevir, simeprevir, or sofosbuvir in combination with pegylated interferon and/or RBV
Evidence of decompensated liver disease or cirrhosis
Co-infected with hepatitis B virus or human immunodeficiency virus (HIV)
History of malignancy <=5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or under evaluation for other active or suspected malignancy
Evidence of hepatocellular carcinoma (HCC) or under evaluation for HCC
Currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study
Clinically-relevant drug or alcohol abuse within 12 months of screening
Pregnant, breast-feeding, or expecting to conceive or donate eggs or sperm from at least 2 weeks prior to Day 1 and continue throughout treatment and follow up, or longer if dictated by local regulations
Male participant whose female partner (s) is/are pregnant
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)
Hemoglobinopathy, including, but not limited to, thalassemia major
Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
Evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
25895428	Background	Forns X, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Buti M. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J Hepatol. 2015 Sep;63(3):564-72. doi: 10.1016/j.jhep.2015.04.009. Epub 2015 Apr 18.
28193518

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	GZR 100 mg + EBR 50 mg + RBV for 12 Weeks	Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	GZR 100 mg + EBR 50 mg + RBV for 12 Weeks	Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks

Units	Counts
Participants	BG00079

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12)

SVR12 is defined as participants having hepatitis C virus ribonucleic acid (HCV RNA) level lower than the limit of quantification (LLoQ, <15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy.

Per protocol population excludes participants due to important deviations from the protocol that may substantially affect the results of the primary and key secondary efficacy endpoints.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 24 weeks

ID	Title	Description
OG000	GZR 100 mg + EBR 50 mg + RBV for 12 Weeks	Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks

Units	Counts
Participants	OG00070

Title

Denominators

Categories

Title	Measurements
	OG00097.1(90.1 to 99.7)

Primary

Percentage of Participants Experiencing Adverse Events

Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.

All participants as treated population defined as all participants who received at least one dose of study medication.

Posted

Number

Percentage of participants

Up to 40 weeks (from Day 1 [post-dose] through 24 [-12/+4] weeks following last dose of study drug)

ID	Title	Description
OG000	GZR 100 mg + EBR 50 mg + RBV for 12 Weeks	Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks

Units	Counts
Participants	OG000

Primary

Percentage of Participants Discontinuing Study Drug Due to an Adverse Event

All participants as treated population defined as all participants who received at least one dose of study medication.

Posted

Number

Percentage of participants

Up to 12 weeks

ID	Title	Description
OG000	GZR 100 mg + EBR 50 mg + RBV for 12 Weeks	Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy

SVR12 is defined as participants having HCV RNA level lower than the LLoQ (<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy. Prior DAA therapy regimen included boceprevir, telaprevir, simeprevir, or sofosbuvir taken concomitantly with peginterferon and ribavirin. Below categories specify with our without resistance-associated variants (RAVs) of the hepatitis C virus.

Per protocol population excludes participants due to important deviations from the protocol that may substantially affect the results of the primary and key secondary efficacy endpoints.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 24 weeks

ID	Title	Description
OG000	GZR 100 mg + EBR 50 mg + RBV for 12 Weeks	Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks

Units	Counts
Participants	OG000

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	GZR 100 mg + EBR 50 mg + RBV for 12 Weeks	Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks			6	79	47	79

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Appendicitis	Infections and infestations	MedDRA 17.1, 18.0	Systematic Assessment	EG0001 events1 affected79 at risk
Pharyngitis bacterial	Infections and infestations	MedDRA 17.1, 18.0	Systematic Assessment	EG0001 events1 affected79 at risk
Urinary tract infection	Infections and infestations	MedDRA 17.1, 18.0	Systematic Assessment	EG0001 events1 affected79 at risk
Laryngeal squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1, 18.0	Systematic Assessment	EG0001 events1 affected79 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1, 18.0	Systematic Assessment	EG0001 events1 affected79 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 17.1, 18.0	Systematic Assessment	EG0001 events1 affected79 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 17.1, 18.0	Systematic Assessment	EG0006 events6 affected79 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 17.1, 18.0	Systematic Assessment	EG0005 events5 affected79 at risk
Constipation	Gastrointestinal disorders	MedDRA 17.1, 18.0	Systematic Assessment	EG0005 events5 affected79 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 17.1, 18.0	Systematic Assessment	EG00011 events6 affected79 at risk
Nausea	Gastrointestinal disorders	MedDRA 17.1, 18.0	Systematic Assessment	EG00010 events9 affected79 at risk
Vomiting	Gastrointestinal disorders	MedDRA 17.1, 18.0	Systematic Assessment	EG0004 events4 affected79 at risk
Asthenia	General disorders	MedDRA 17.1, 18.0	Systematic Assessment	EG00012 events12 affected79 at risk
Fatigue	General disorders	MedDRA 17.1, 18.0	Systematic Assessment	EG00024 events22 affected79 at risk
Haemoglobin decreased	Investigations	MedDRA 17.1, 18.0	Systematic Assessment	EG0004 events4 affected79 at risk
Headache	Nervous system disorders	MedDRA 17.1, 18.0	Systematic Assessment	EG00016 events15 affected79 at risk
Insomnia	Psychiatric disorders	MedDRA 17.1, 18.0	Systematic Assessment	EG0007 events7 affected79 at risk

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D006525	Hepatitis, Viral, Human
D014777	Virus Diseases
D018178	Flaviviridae Infections
D012327	RNA Virus Infections
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases

ID	Term
D012263	Ribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides