Clinical trial NCT02964091: Simplifying Hepatitis C Antiviral Therapy in Rwanda for Elsewhere in the Developing World
Official title: Simplifying Hepatitis C Antiviral Therapy in Rwanda for Elsewhere in the Developing World
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hepatitis C
Keywords: Hepatitis C Virus
sofosbuvir/ledipasvir
Efficacy
Lead sponsor: Partners in Health
Sponsor class: OTHER
First posted: 2016-11-15
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: After study completion (24 weeks)
measure: 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
timeFrame: After study completion (24 weeks)
measure: Proportion of participants with a new grade 3 or 4 adverse event or premature study drug discontinuation due to an adverse event.
timeFrame: After study completion (24 weeks)
Secondary outcomes:
measure: A set of minimum required monitoring tests
timeFrame: After study completion (24 weeks)
measure: Distribution of HCV genotypes subtypes among participants
timeFrame: After study completion (24 weeks)
measure: SVR12, stratified by genotypic subtype
timeFrame: After study completion (24 weeks)
measure: Basic demographic and clinical characteristics of patients referred for HCV treatment
timeFrame: After study completion (24 weeks)
measure: Adherence to SOF/LDV measured by pill count
timeFrame: After 12 weeks medication therapy
measure: Proportion of participants with virologic failure
timeFrame: After study completion (24 weeks)
measure: Proportion of participants with HCV RNA below the level of quantitation (BLQ) while on treatment
timeFrame: After study completion (24 weeks)
measure: Proportion of HIV co-infected participants that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment
timeFrame: After 12 weeks of medication therapy
measure: Proportion of participants reporting increased quality of life after SVR12 using the Medical Outcomes Study HIV Health Survey
timeFrame: After study completion (24 weeks)
Other outcomes:
Locations:
city: Kanombe
country: Rwanda
facility: Rwanda Military Hospital
state: Kigali
Study officials:
affiliation: Partners in Health
name: Neil Gupta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rwanda Military Hospital
name: Jules Kabahizi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rwanda Biomedical Centre
name: Aimable Mbituyumuremyi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Philip Grant, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rwanda
name: Claude M Muvunyi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.