Simplifying Hepatitis C Antiviral Therapy in Rwanda for Elsewhere in the Developing World (SHARED)

The main purpose of the study is to evaluate the efficacy, safety and tolerability of a medication, ledipasvir/sofosbuvir (LDV/SOF), used to treat individuals with chronic hepatitis C virus (HCV) in Rwandan adults. A sub-cohort of participants will have limited laboratory monitoring to determine the minimum laboratory tests necessary.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: sofosbuvir/ledipasvir

Detailed Description

This is an open-label single arm study that will evaluate the antiviral efficacy, safety and tolerability of ledipasvir/sofosbuvir fixed dose combination administered for 12 weeks in HCV treatment-naive and treatment-experienced participants with chronic genotype 1 or 4 HCV infection. Approximately 240 participants will be enrolled and treated with sofosbuvir (SOF) 400 mg/LDV 90 mg fixed dose combination (FDC) one tablet once daily for 12 weeks in the SHARED 1 study. Sixty additional participants will be enrolled in the SHARED 2 sub-cohort with laboratory monitoring blinded to study clinicians.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 4

Contacts and Locations

Study Locations

• Rwanda
  • Kigali
    • Kanombe, Kigali, Rwanda, 00000
      • Rwanda Military Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients that are willing and able to provide written informed consent
• age ≥ 18 years
• HCV RNA ≥ 103 IU/mL
• HCV genotype 1 or 4
• screening ultrasound excluding hepatocellular carcinoma (HCC)
• acceptable laboratory values (hemoglobin ≥8.0 g/dL, platelet count ≥40,000/mm3; AST, ALT, and alkaline phosphatase ≤10 × ULN; creatinine clearance ≥30 mL/min)
• general good health
• ability to comply with study procedures
• HIV-infected patients must have completed at least 6 months of any approved HIV antiretroviral therapy (ART) per Rwanda National Guidelines 2013, have been taking for at least 2 weeks prior to screening ART compatible with SOF/LDV (efavirenz, rilpivirine, raltegravir, dolutegravir, emtricitabine, lamivudine, zidovudine, tenofovir), have screening HIV RNA < 200 copies/mL, and have screening CD4 T-cell count of ≥100 cells/µL

Exclusion Criteria:

• current or history of clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage)
• active tuberculosis
• other clinically-significant illness (except HCV and/or HIV) or any other major medical disorder
• active Hepatitis B infection
• difficulty with blood collection and/or poor venous access for the purposes of phlebotomy
• any IFN-containing regimen within 8 weeks prior to screening or any prior exposure to HCV-specific direct-acting antiviral agent (other than a NS3/4A protease inhibitor and SOF), current pregnancy or breastfeeding, and active drug or alcohol use or dependence

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Harvoni; sofosbuvir/ledipasvir once daily for 12 weeks	Drug: sofosbuvir/ledipasvir; Other Names: Harvoni

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with sustained viral response as defined by an HCV RNA below the limit of quantification 12 weeks after discontinuation of study treatment	To determine the hepatitis C virus (HCV) antiviral efficacy of sofosbuvir/ledipasvir (SOF/LDV) fixed-dose combination (FDC) as measured by the proportion of participants with sustained viral response 12 weeks after discontinuation of study treatment (SVR12) in Rwanda.	After study completion (24 weeks)
Proportion of participants with sustained viral response as defined by an HCV RNA below the limit of quantification 12 weeks after discontinuation of study treatment, with limited lab monitoring	To determine the HCV antiviral efficacy of SOF/LDV FDC, as measured by the proportion of participants with sustained viral response 12 weeks after discontinuation of study treatment (SVR12), with limited lab monitoring in Rwanda.	After study completion (24 weeks)
Proportion of participants with a new grade 3 or 4 adverse event or premature study drug discontinuation due to an adverse event.	To evaluate the safety and tolerability of SOF/LDV FDC in Rwanda	After study completion (24 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A set of minimum required monitoring tests	A set of minimum required monitoring tests	After study completion (24 weeks)
Distribution of HCV genotypes subtypes among participants	Distribution of HCV genotypes subtypes among participants	After study completion (24 weeks)
SVR12, stratified by genotypic subtype	SVR12, stratified by genotypic subtype	After study completion (24 weeks)
Basic demographic and clinical characteristics of patients referred for HCV treatment	Basic demographic and clinical characteristics of patients referred for HCV treatment	After study completion (24 weeks)
Adherence to SOF/LDV measured by pill count	Adherence to SOF/LDV measured by pill count	After 12 weeks medication therapy
Proportion of participants with virologic failure	Proportion of participants with virologic failure	After study completion (24 weeks)
Proportion of participants with HCV RNA below the level of quantitation (BLQ) while on treatment	Proportion of participants with HCV RNA below the level of quantitation (BLQ) while on treatment	After study completion (24 weeks)
Proportion of HIV co-infected participants that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment	Proportion of HIV co-infected participants that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment	After 12 weeks of medication therapy
Proportion of participants reporting increased quality of life after SVR12 using the Medical Outcomes Study HIV Health Survey	To determine the effect of SOF/LDV and SVR12 on quality of life in Rwanda	After study completion (24 weeks)

Collaborators and Investigators

• Sponsor: Partners in Health
• Investigators: Principal Investigator: Neil Gupta, MD, Partners In Health; Principal Investigator: Jules Kabahizi, MD, Rwanda Military Hospital; Principal Investigator: Aimable Mbituyumuremyi, MD, Rwanda Biomedical Centre; Principal Investigator: Philip Grant, MD, Stanford University; Principal Investigator: Claude M Muvunyi, MD, University of Rwanda

Publications and helpful links

General Publications

• Gupta N, Mbituyumuremyi A, Kabahizi J, Ntaganda F, Muvunyi CM, Shumbusho F, Musabeyezu E, Mukabatsinda C, Ntirenganya C, Van Nuil JI, Kateera F, Camus G, Damascene MJ, Nsanzimana S, Mukherjee J, Grant PM. Treatment of chronic hepatitis C virus infection in Rwanda with ledipasvir-sofosbuvir (SHARED): a single-arm trial. Lancet Gastroenterol Hepatol. 2019 Feb;4(2):119-126. doi: 10.1016/S2468-1253(18)30382-0. Epub 2018 Dec 11.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): August 28, 2020
• Study Completion (Actual): August 28, 2020

Study Registration Dates

• First Submitted: November 3, 2016
• First Submitted That Met QC Criteria: November 10, 2016
• First Posted (Estimate): November 15, 2016

Study Record Updates

• Last Update Posted (Actual): September 21, 2021
• Last Update Submitted That Met QC Criteria: September 14, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Efficacy; Hepatitis C Virus; sofosbuvir/ledipasvir
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Ledipasvir
• Other Study ID Numbers: SHARED 092415

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The study protocol, study data, data dictionary, data collection instruments, and informed consent forms are available upon request from the corresponding author. De-identifiable individual participant data will be made available 9 months after the publication date and ending 36 months after the publication date. Forms and data can be accessed by written request to the corresponding author and the study sponsor, Partners In Health. The data will be made available following evaluation and approval of proposed use by the study sponsor and signed data access agreement with the study sponsor.
• IPD Sharing Time Frame: De-identifiable individual participant data will be made available 9 months after the publication date and ending 36 months after the publication date.

IPD Sharing Access Criteria

Forms and data can be accessed by written request to the corresponding author and the study sponsor, Partners In Health.

The data will be made available following evaluation and approval of proposed use by the study sponsor and signed data access agreement with the study sponsor.

• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No