Clinical Trial to eLiminate HCV-infection in Treatment-naïve, Renally Impaired EgyptiAn Patients on Renal Dialysis, With Chronic Hepatitis C Genotype 4

NCT03381859 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: HP-00076974
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Efficacy Objective

• To assess whether a 12-week treatment course with oral 50 mg elbasvir plus 100 mg grazoprevir given in a single daily dose to treatment-naïve patients with end-stage renal disease (ESRD) and infected with genotype 4 (GT4) chronic HCV (CHC) infection can produce a sustained viral response (SVR), i.e. HCV RNA below the lower limit of quantification \[LLOQ\] for 12 weeks (SVR12) after completion of the study treatment course Secondary Objectives
• To assess the efficacy of elbasvir/grazoprevir in suppressing HCV viremia in treatment-naïve GT4 CHC patients at each scheduled visit and clinically meaningful endpoints (Week 2, 8 and 12 \[End of Treatment - EOT\]) and 24 (SVR12)
• To assess the safety and tolerability of a 12-week treatment course with elbasvir/grazoprevir in treatment-naïve patients with ESRD and infected with GT4 CHC.
• To assess liver fibrosis by non-invasive evaluation of liver stiffness (Fibroscan®) in the same patients before treatment and EOT and SVR12 Clinical hypotheses. Primary Efficacy Hypothesis \- A 12-week treatment course with elbasvir/grazoprevir in treatment-naïve patients with ESRD and infected with GT4 CHC infection will result in an HCV RNA below the LLOQ in 95% of patients within 2 weeks of treatment, and at least 95% will have an SVR12. Secondary hypotheses
• A 12-week treatment course with elbasvir/grazoprevir in ESRD GT4 treatment-naïve patients will result in undetectable viremia in 95% patients at Week 2, 4, 8 and 12 (EOT) and 24 (SVR12)
• Treatment will be safe and well-tolerated in these patients, as determined by the type and number of adverse events identified through laboratory testing, vital signs and physical examinations.
• In these patients with liver fibrosis before treatment, the liver fibrosis as assessed by non-invasive evaluation of liver stiffness (Fibroscan®) will improve by EOT and SVR12

Conditions

Hepatitis C Virus Infection, Response to Therapy of

Keywords

Hepatitis C Virus; Genotype 4; End Stage Renal Disease

Outcome Measures

Primary Outcomes (1)

• SVR12

  absence of HCV plasma RNA 12 weeks after end of treatment

  24 weeks from treatment initiation date

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Patients to receive 12 weeks of Elbasvir (50mg) / Grazoprevir (100mg)

Drug: Elbasvir/Grazoprevir 50 MG-100 MG Oral Tablet [ZEPATIER]

Interventions

Elbasvir/Grazoprevir 50 MG-100 MG Oral Tablet [ZEPATIER] DRUG

Hepatitis C Virus direct-acting antiviral

Treatment Arm

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent obtained before undergoing any trial-related procedures
• Male and female patients; age between 21 and 70 years inclusive
• Chronic hepatitis C infection with genotype 4 confirmed by genotypic testing at screening or within 6 months of screening period
• Treatment naïve - absence of prior failed treatment for HCV with Interferon plus ribavirin therapy or directly acting antivirals (treatment experienced)
• Detectable HCV viral load (quantitative)
• Liver cirrhosis subjects may be included but will be limited to those with compensated liver disease
• Chronic kidney disease with end-stage liver disease (defined as glomerular filtration rate \[eGFR\] \<=15 mL/min/1.73m2) on hemodialysis for at least 3 months, including individuals awaiting kidney transplant and those with failed kidney transplants but no longer on immunosuppressant therapy)
• Screening laboratory values within the defined protocol thresholds
• Women of child-bearing potential, must agree to abstinence or use of effective contraceptive methods (e.g. oral or injectable contraceptives, intra-uterine device (IUD), transdermal contraceptive patch) at least 2 weeks prior Day 1 through 14 days after the last dose of the study drug.
• Ability to communicate, participate, and comply with the requirements of the entire study

You may not qualify if:

• Patients didn't sign informed consent or under age of legal consent
• Pregnant or breastfeeding woman
• Has HCV genotypes other than G4
• On peritoneal dialysis for management of kidney disease
• Co-Infection with HIV and/or HBV (with positive HBsAg)
• Evidence of hepatocellular carcinoma (HCC)
• Evidence of hepatic decompensation as evidenced by presence or history of ascites, esophaegal or gastric bleeding, hepatic encelopathy or other signs of or symptoms of advanced liver disease, or cirrhotic subjects with Child-Pugh B or C, or who have a Purgh-Turcotte (CPT) score \>6
• Active or suspected non-hepatic malignancy or history of any malignancy except for cured basal cell or squamous cell skin cancer or in situ cervical cancer
• Organ transplant (including hematopoietic stem cell transplant) other than kidney, cornea, and hair
• Conditions requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
• Uncontrolled or poorly controlled hypertension
• Pregnant, breast-feeding, expecting to conceive or donate eggs, or donate sperm from Day 1 through 14 days after the last study dose.
• Significant cardiovascular disorder (e.g. myocardial infarction or unstable angina) or interventional cardiovascular procedure within 3 months prior to signing informed consent
• Recent (within 3 months prior to signing informed consent) episode or recurrence of stroke, transient ischemic attack (TIA) or neurological disorder, including but not limited to seizures
• ALT or AST \> 10-fold the upper limit of normal

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Merck Sharp & Dohme LLC: collaborator
• Cairo University: collaborator

Study Sites (1)

Kasr Alainy Hospital

Cairo, Almanial, Egypt

Location

MeSH Terms

Conditions

Hepatitis C; Kidney Failure, Chronic

Interventions

elbasvir; grazoprevir; elbasvir-grazoprevir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Shyamasundaran Kottilil, MD, PhD

  University of Maryland, College Park

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: December 22, 2017
• Study Start: December 1, 2019
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: April 20, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)