Clinical trial NCT03186365: 8 Weeks Versus 12 Weeks of Elbasvir/Grazoprevir in Treatment-naïve CHC With Mild Fibrosis
Official title: Efficacy of 8 Weeks Versus 12 Weeks of Elbasvir/Grazoprevir in Treatment-naïve Chronic Hepatitis C Genotype 1b Patients With Mild Fibrosis: an Open-label, Randomized, Active Control Trial (EGALITE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C, Chronic
Lead sponsor: Kaohsiung Medical University Chung-Ho Memorial Hospital
Sponsor class: OTHER
First posted: 2017-06-14
Enrollment: 82
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Grazoprevir plus elbasvir 12 to 16 weeks is now approved for chronic hepatitis C (CHC) genotype 1, 4, or 6 infection regardless liver disease severity. The current study aims to explore the efficacy and safety of 8-week grazoprevir/elbasvir in HCV-1b patients with mild liver fibrosis

Detailed description: Grazoprevir, an HCV nonstructural protein 3/4A (NS3/4A) inhibitor 100 mg, plus elbasvir, an HCV NS5A inhibitor 50 mg fixed dose combination, Zepatier, achieved high SVR12 rates of \> 95 % in treatment-naïve, experienced cirrhotic and non-cirrhotic patients with genotype 1, 4, or 6 infection. Zepatier, 12 to 16 weeks, was approved for the treatment of HCV genotype 1 and 4 in Taiwan in December, 2016. An SVR rate of 93 % was demonstrated in treatment-naive, non-cirrhotic (F0-F3) GT1b-infected patients who received 8 weeks of grazoprevir/elbasvir with or without ribavirin in the pooled analysis of C-WORTHY (PN035) and C-EDGE treatment-naive (PN060) trials. Furthermore, truncated treatment period of 8-week grazoprevir/elbasvir could achieve an even higher SVR rate at \> 98% for naive HCV G1b patients with mild fibrosis (Fibrosis score 0-2). The study aims to evaluate the efficacy of 8-week regimen with grazoprevir/elbasvir on naïve, HCV G1b patients with mild fibrosis by a randomized clinical trial.

Eligibility criteria: Inclusion Criteria:

* Treatment naïve, HCV genotype 1b patients
* History of chronic HCV infection \> 6 months
* Aged at least 20 years
* HCV RNA of 10,000 IU/mL or greater
* Fibroscan examination \< 9.5 Kpa
* Negative serum or urine pregnancy test result (sensitivity of 25 mIU or better) for women with childbearing potential within the 24-hour period before the first dose of study drugs
* Female patients with childbearing potential must agree to use two reliable forms of effective non-hormonal contraception (i.e., condoms, cervical barriers, intrauterine device, spermicides, or sponge), at least 1 of which must be a physical barrier method, during treatment till end of follow up.
* A hormonal contraception (in lieu of non-hormonal) plus a physical barrier method can be used after end of treatment. All men with female partners of childbearing potential must use two reliable forms of effective contraception (combined) during treatment and till end of follow up
* Ability to participate and willingness to give written informed consent and to comply with the study restrictions.

Exclusion Criteria:

* Prior experience of IFN or direct antiviral agents (DAA)
* Hepatitis B virus or HIV co-infection.
* Patients with experience of ascites, esophageal varices, or other evidence of hepatic decompensation, and/or hepatocellular carcinoma.
* History of organ transplantation, except cornea transplantation.
* Hemoglobulin concentration \< 11 mg/dl
* Platelet count \< 75,000/mm3
* Albumin \< 3 mg/dL
* History of active malignancy within the last 5 years, with the exception of localized or in situ carcinoma (e.g., basal or squamous cell carcinoma of the skin)
* Poorly controlled diabetes (Hemoglobin A1c value ≥ 8.5%) and endocrine condition.
* Total bilirubin \>2 mg/dL, unless subject has a documented history of Gilbert's disease.
* Pregnant or lactating women.

Primary outcomes:
measure: the rate of subjects with undetectable HCV RNA 12 weeks post end-of-treatment
timeFrame: through study completion, an average of 5.5 months
Secondary outcomes:
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
Study officials:
affiliation: Kaohsiung Medical University
name: Ming-Lung Yu, MD., PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huang CF, Hung CH, Cheng PN, Bair MJ, Huang YH, Kao JH, Hsu SJ, Lee PL, Chen JJ, Chien RN, Peng CY, Lin CY, Hsieh TY, Cheng CH, Dai CY, Huang JF, Chuang WL, Yu ML. An Open-Label, Randomized, Active-Controlled Trial of 8 Versus 12 Weeks of Elbasvir/Grazoprevir for Treatment-Naive Patients With Chronic Hepatitis C Genotype 1b Infection and Mild Fibrosis (EGALITE Study): Impact of Baseline Viral Loads and NS5A Resistance-Associated Substitutions. J Infect Dis. 2019 Jul 19;220(4):557-566. doi: 10.1093/infdis/jiz154.