NCT02601573

Brief Summary

This is a randomized, multi-site, open-label trial of the co-administration of a fixed-dose combination (FDC) of EBR 50 mg + GZR (100 mg) (EBR/GZR) and SOF 400 mg, with and without RBV, in treatment-naïve (TN) and treatment-experienced (TE) participants with chronic HCV GT3 infection with compensated cirrhosis.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
101

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2016

Shorter than P25 for phase_2

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 9, 2015

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 10, 2015

Completed
2 months until next milestone

Study Start

First participant enrolled

January 5, 2016

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 18, 2016

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 6, 2017

Completed
10 months until next milestone

Results Posted

Study results publicly available

November 13, 2017

Completed
Last Updated

August 13, 2019

Status Verified

August 1, 2019

Enrollment Period

10 months

First QC Date

November 9, 2015

Results QC Date

October 12, 2017

Last Update Submit

August 5, 2019

Conditions

Outcome Measures

Primary Outcomes (3)

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

    The percentage of participants achieving SVR12 (i.e., HCV ribnonucleic acid \[RNA\] \< Lower Limit of Quantification \[LLOQ\] 12 weeks after completing study treatment) was determined. Plasma HCV RNA levels were determined with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.

    Up to Week 28

  • Percentage of Participants Experiencing an Adverse Event (AE)

    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.

    Up to 18 weeks (up to 2 weeks after completion of study treatment)

  • Percentage of Participants Discontinuing From Study Therapy Due to an AE

    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.

    Up to 16 weeks

Secondary Outcomes (1)

  • Percentage of Participants Achieving SVR24 (Sustained Virologic Response 24 Weeks After the End of All Study Therapy)

    Up to Week 40

Study Arms (5)

Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks

EXPERIMENTAL

TN HCV GT3 participants will take 1 fixed-dose combination (FDC) tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg once-daily (q.d.) with RBV (200 mg capsules; weight-based dosing) twice-daily (b.i.d.) for 8 weeks.

Drug: GrazoprevirDrug: ElbasvirDrug: RibavirinDrug: Sofosbuvir

Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks

EXPERIMENTAL

TN HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks.

Drug: GrazoprevirDrug: ElbasvirDrug: Sofosbuvir

Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks

EXPERIMENTAL

TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks.

Drug: GrazoprevirDrug: ElbasvirDrug: Sofosbuvir

Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks

EXPERIMENTAL

TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks.

Drug: GrazoprevirDrug: ElbasvirDrug: RibavirinDrug: Sofosbuvir

Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks

EXPERIMENTAL

TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks.

Drug: GrazoprevirDrug: ElbasvirDrug: Sofosbuvir

Interventions

GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.

Also known as: MK-5172
Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 WeeksArm 2: HCV GT3 TN EBG/GZR+SOF 12 WeeksArm 3: HCV GT3 TE EBG/GZR+SOF 12 WeeksArm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 WeeksArm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks

EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.

Also known as: MK-8742
Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 WeeksArm 2: HCV GT3 TN EBG/GZR+SOF 12 WeeksArm 3: HCV GT3 TE EBG/GZR+SOF 12 WeeksArm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 WeeksArm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks

RBV 200 mg capsules taken b.i.d. (morning and evening) by mouth at a total daily dose ranging from 800 mg to 1400 mg (total daily dose was based on participant body weight).

Also known as: Rebetol®
Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 WeeksArm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks

SOF 400 mg tablet taken q.d. by mouth in the morning with food.

Also known as: Sovaldi®, Harvoni®
Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 WeeksArm 2: HCV GT3 TN EBG/GZR+SOF 12 WeeksArm 3: HCV GT3 TE EBG/GZR+SOF 12 WeeksArm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 WeeksArm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • has HCV RNA (\>= 10,000 IU/mL in peripheral blood) at screening
  • has documented HCV GT3 (with no evidence of non-typeable or mixed GT infection)
  • has compensated cirrhosis of the liver
  • has liver imaging within 6 months of Day 1 with no evidence of hepatocellular carcinoma (HCC)
  • is either HCV TN or TE (i.e., has documented prior virologic failure or intolerance to peg-interferon/ribavirin)
  • is otherwise healthy as determined by medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements
  • has compensated cirrhosis of the liver
  • is TN or TE (i.e., documented prior virologic failure or intolerance to peg-interferon/ribavirin)
  • is not of reproductive potential, or agrees to not impregnate a partner or become pregnant for at least 2 weeks prior to the first dose of study drug, and for 7 months after the final dose of study drug (or longer if dictated by local regulations)

You may not qualify if:

  • has previously received one or more doses of a direct-acting antiviral (DAA)
  • has evidence of decompensated liver disease
  • is coinfected with hepatitis B (hepatitis B surface antigen \[HBsAg\] positive)
  • has a recent (within 5 years) history of malignancy or is under evaluation for HCC or other suspected malignancy
  • is currently or has participated (within past 30 days) in a study with an investigational compound
  • has clinically-relevant drug or alcohol abuse within the past 12 months of screening
  • is a female and is pregnant or breast-feeding
  • is a male whose female partner is/are pregnant
  • has any of the following:
  • organ transplants
  • poor venous access
  • history of gastric surgery or malabsorption disorder
  • current or history of clinically significant cardiac abnormalities or dysfunction
  • chronic pulmonary disease
  • hemoglobinopathy
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • Foster GR, Agarwal K, Cramp ME, Moreea S, Barclay S, Collier J, Brown AS, Ryder SD, Ustianowski A, Forton DM, Fox R, Gordon F, Rosenberg WM, Mutimer DJ, Du J, Gilbert CL, Asante-Appiah E, Wahl J, Robertson MN, Barr E, Haber B. Elbasvir/grazoprevir and sofosbuvir for hepatitis C virus genotype 3 infection with compensated cirrhosis: A randomized trial. Hepatology. 2018 Jun;67(6):2113-2126. doi: 10.1002/hep.29852. Epub 2018 Apr 19.

MeSH Terms

Conditions

Hepatitis C

Interventions

grazoprevirelbasvirRibavirinSofosbuvirledipasvir, sofosbuvir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

RibonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesUridine MonophosphateUracil NucleotidesPyrimidine NucleotidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleotidesRibonucleotides

Results Point of Contact

Title
Senior Vice President, Global Clinical Development
Organization
Merck Sharp & Dohme Corp.

Study Officials

  • Medical Director

    Merck Sharp & Dohme LLC

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 9, 2015

First Posted

November 10, 2015

Study Start

January 5, 2016

Primary Completion

October 18, 2016

Study Completion

January 6, 2017

Last Updated

August 13, 2019

Results First Posted

November 13, 2017

Record last verified: 2019-08

Data Sharing

IPD Sharing
Will share

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

More information