A Phase 3, Global, Multicenter, Open-Label Study to Investigate the Efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, With Non-severe Fibrosis
Overview
- Phase
- Phase 3
- Intervention
- Elbasvir/Grazoprevir Fixed Dose Combination
- Conditions
- Chronic HCV Infection
- Sponsor
- University Hospital, Clermont-Ferrand
- Enrollment
- 117
- Locations
- 1
- Primary Endpoint
- Evaluation of the Efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve as Measured by the Proportion of Subjects With Sustained Viral Response 12 Weeks After Cessation of Treatment (SVR 12).
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
A Phase 3, Global, Multicenter, Open-Label Study to Investigate the Efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non-severe fibrosis
The primary objectives of this study are as follows:
- To evaluate the efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).
- To evaluate the safety and tolerability of EBV/GZR treatment
The secondary objectives of this study are as follows:
- To determine the proportion of subjects who attain SVR at 4 and 24 weeks after cessation of treatment (SVR4 and SVR24)
- To evaluate the proportion of subjects with virologic failure
- To evaluate the kinetics of circulating HCV RNA during treatment and after cessation of treatment.
- To evaluate the emergence of viral resistance to EBV/GZR during treatment and after cessation of treatment
Detailed Description
One hundred twenty treatment-naïve subjects with chronic HCV GT1b infection without cirrhosis will be enrolled. There will be one treatment group with EBV/GZR (50/100 mg) once daily without regards to food for 8 weeks. EBV/GZR is manufactured as a 50/100 mg tablet for oral administration. Subjects will take 1 tablet daily. Screening assessments will be completed within 28 days of the Day 1 visit. The screening window can be extended to 42 days for subjects requiring a liver biopsy, or extenuating circumstances. All subjects will complete the following study visits: Screening, Day 1, and on-treatment visits at the end of week 2, week 4 and week 8. Post-treatment visits will occur at Weeks 4, 12, and 24 after last dose of study drug. All subjects will complete the posttreatment Week 4 and 12 visits. Subjects who achieve SVR12 (HCV RNA \< LLOQ at posttreatment Week12) will complete the posttreatment Week 24 visit. Screening assessments will include physical examination, medical history, height, weight, vital signs, adverse events related to screening procedures, concomitant medications, safety laboratory tests (including hematology, chemistry, and coagulation), HCV RNA, serology (HCV, HBV), serology and/or antigen testing for HIV, HCV genotyping, hemoglobin A1c (HbA1c), assessment of the absence of cirrhosis or severe fibrosis (including Fibrotest® and Fibroscan®), serum β-human chorionic gonadotropin (β-hCG) (females of child-bearing potential only), urinalysis. On-treatment assessments include adverse events (AEs), concomitant medications, study medication dispensation and pill count, physical examination, weight, vital signs, safety laboratory tests, HCV RNA, and urine pregnancy tests (females of child bearing potential only). Post-treatment assessments include AEs, concomitant medications, vital signs, safety laboratory tests (including hematology, chemistry, and coagulation), HCV RNA, and urine pregnancy tests (females of child-bearing potential only).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to provide written informed consent
- •Male or female, age ≥ 18 years
- •Body Mass Index (BMI) ≥ 18 kg/m2
- •HCV RNA ≥ 100 000 IU/mL at Screening
- •Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy, only genotype 1b virus. (Positive for anti HCV antibody, HCV RNA, or an HCV genotype)
- •Treatment-naïve with no prior exposure to any IFN, RBV, or approved or experimental HCV-specific DAA
- •Non severe fibrosis (F\<2) according to combination of this two tests :
- •Fibroscan lower than 9.5kPa and Fibrotest lower than 0.59
- •Females of childbearing potential (as defined in protocol Appendix 4) must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 prior to enrollment
- •Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use 2 effective method(s) of contraception from at least two weeks prior to Day 1 through 14 days after the last dose of study drugs.
Exclusion Criteria
- •Is under the age of legal consent, is mentally or legally incapacitated, has significant emotional problems at the time of pre-study screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, would interfere with the study procedures.
- •Current or prior history of any of the following:
- •Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded
- •Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug
- •Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy
- •History of decompensation (e.g., clinical ascites, encephalopathy, and/or variceal hemorrhage)
- •Solid organ transplantation (including hematopoietic stem cell transplants) other than kidney, cornea and hair.
- •Significant cardiac disease
- •Unstable psychiatric condition including hospitalization, suicidal attempt, and/or a period of disability as a result of their psychiatric illness within 2 years prior to Screening
- •Malignancy within the 5 years prior to Screening, with the exception of specific cancers that have been cured by surgical resection (e.g., basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are not eligible
Arms & Interventions
Elbasvir/Grazoprevir
evaluate the efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).
Intervention: Elbasvir/Grazoprevir Fixed Dose Combination
Outcomes
Primary Outcomes
Evaluation of the Efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve as Measured by the Proportion of Subjects With Sustained Viral Response 12 Weeks After Cessation of Treatment (SVR 12).
Time Frame: at 12 weeks post-treatment
Blood samples for HCV RNA determination were collected 12 weeks after cessation of treatment and analysed by local laboratories tests
Secondary Outcomes
- Percentage of Subjects Who Attain SVR 24 Weeks After Cessation of Treatment (SVR 24)(at 24 weeks after cessation of treatment)
- Percentage of Subjects Who Attain SVR at 4 Weeks After Cessation of Treatment (SVR4)(at 4 weeks after cessation of treatment)
- Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Asthenia Reported(Between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks)
- Percentage of Subjects With Virologic Failure(at 12 weeks after cessation of treatment)
- Evaluation of the Emergence of Viral Resistance to EBV/GZR at 24 Weeks After Cessation of Treatment(at 24 weeks after end of treatment)
- Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Headache Reported(between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks)
- Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Digestive Disorders Reported(Between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks)