Clinical trial NCT03888729: Simplifying HCV Treatment in Rwanda for Elsewhere in the Developing World: Pangenotypic and Retreatment Study (SHARED3)
Official title: Simplifying Hepatitis C Antiviral Therapy in Rwanda for Elsewhere in the Developing World: Pangenotypic and Retreatment Study (SHARED3)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C
direct-acting antiviral
Rwanda
Lead sponsor: Partners in Health
Sponsor class: OTHER
First posted: 2019-03-25
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be assigned to one of the following two groups in parallel for the duration of the study, based on treatment indication to be put on SOF/VEL or SOF/VEL/VOX:

* sofosbubir/velpatasvir (SOF/VEL) FDC once daily for 12 weeks will be administered to HCV-infected individuals naïve to DAA therapy regimen (in this group we consider also HCV-infected individuals who have failed interferon-based therapy) who meet other eligibility criteria;
* sofosbubir/velpatasvir /voxilaprevir (SOF/VEL/VOX) FDC once daily for 12 weeks will be administered to HCV treatment-experienced participants (i.e. HCV-infected individuals with a history of virologic failure to SOF/LDV or other DAA-containing regimen) who meet other eligibility criteria.
Primary purpose: TREATMENT

Brief summary: The main purpose of the study is to determine the antiviral efficacy and evaluate the safety and tolerability of sofosbuvir/ velpatasvir (SOF/VEL) and sofosbuvir/ velpatasvir/ voxilaprevir (SOF/VEL/VOX) used to treat individuals with chronic hepatitis C virus infection in Rwanda adults.

Detailed description: This is an open-label single-arm study that will examine the antiviral efficacy, safety and tolerability of 12 weeks daily therapy with fixed dose combination (FDC) of SOF/VEL and SOF/VEL/VOX administered respectively in HCV-infected treatment-naïve adult participants and in HCV-infected individuals with a history of virologic failure to SOF/LDV or other DAA-containing regimen. A total of 100 participants will be enrolled in this portion of the SHARED study, labelled the "SHARED 3 study": 60 treatment-naïve participants and 40 individuals with history of virologic failure to SOF/LDV or other DAA-containing regimen

Eligibility criteria: Inclusion Criteria:

* Willing and able to provide written informed consent
* Age ≥ 18 years
* HCV RNA \>1000 IU/mL at Screening
* For SOF/VEL arm, HCV treatment-naïve or interferon/ribavirin-experienced
* For SOF/VEL/VOX arm, history of virologic failure to SOF/LDV or other DAA-containing regimen as defined by a quantifiable HCV viral load any time at or after the end of HCV therapy
* Screening ultrasound excluding hepatocellular carcinoma (HCC)
* Acceptable laboratory values including:

  * Hemoglobin ≥8.0 g/dL
  * Platelet count ≥40,000/mm3
  * AST, ALT, and alkaline phosphatase ≤10 × ULN
  * Calculated creatinine clearance (CrCl) ≥30 mL/min
* General good health
* Ability to comply with the dosing instructions for study drug administration and to complete the study schedule of assessments
* If HIV-infected:

  * The participant must have completed at least 6 months of any approved HIV antiretroviral therapy (ART) before starting enrollment
  * The participant at time of screening and for at least 2 weeks prior to screening must be on ART compatible with SOF/VEL and SOF/VEL/VOX
  * Screening HIV RNA \< 200 copies/mL
  * Screening CD4 T-cell count of ≥100 cells/µL
* Women of reproductive potential must have a negative urine pregnancy test at Screening and a negative urine pregnancy test at Entry prior to enrollment.

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 that, in the opinion of the site investigator, may interfere with participant treatment, assessment or compliance with the protocol; participants currently under evaluation for a potentially clinically-significant illness (other than HCV/HIV) are also excluded.
* Active Hepatitis B infection
* Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy
* Pregnant or nursing female
* Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study procedures and treatment

Primary outcomes:
measure: Proportion of participants with sustained viral response 12 weeks after discontinuation of study treatment (SVR12)
timeFrame: After study completion (week 24)
measure: Proportion of patients treated with SOF/VEL FDC and SOF/VEL/VOX FDC with a new grade 3 or 4 adverse event as defined by the DAIDS Scales or with premature study drug discontinuation due to an adverse event
timeFrame: After study completion (week 24)
Secondary outcomes:
measure: Proportion of participants by HCV genotype subtypes with SVR12 after completing treatment with SOF/VEL FDC and SOF/VEL/VOX FDC
timeFrame: After study completion (week 24)
measure: Adherence to SOF/VEL FDC and SOF/VEL/VOX FDC
timeFrame: After study completion (week 24)
measure: Odds ratio for achievement of SVR12 by treatment type for the following variables: age (per 10 year increase), female sex, HIV co-infection, genotype subtype 4r, baseline HCV viral load (per 1 log increase), APRI > 1.0
timeFrame: After study completion (week 24)
measure: Proportion of HIV co-infected subjects that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment
timeFrame: After study completion (week 24)
measure: Effect of SOF/VEL FDC and SOF/VEL/VOX FDC and SVR12 on quality of life
timeFrame: After study completion (week 24)
Other outcomes:
Locations:
city: Kigali
country: Rwanda
facility: Rwanda Military Hospital
Study officials:
affiliation: Partners In Health; Brigham and Women's Hospital; Harvard Medical School
name: Neil Gupta, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Partners In Health/Inshuti Mu Buzima - Rwanda
name: Fredrick Kateera, MD, PhD
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.
citation: Kateera F, Shumbusho F, Manirambona L, Kabihizi J, Murangwa A, Serumondo J, Makuza JD, Nsanzimana S, Muvunyi CM, Kabakambira JD, Sylvain H, Camus G, Grant PM, Gupta N. Safety and efficacy of sofosbuvir-velpatasvir to treat chronic hepatitis C virus infection in treatment-naive patients in Rwanda (SHARED-3): a single-arm trial. Lancet Gastroenterol Hepatol. 2022 Jun;7(6):533-541. doi: 10.1016/S2468-1253(21)00398-8. Epub 2022 Mar 3.
citation: Gupta N, Manirambona L, Shumbusho F, Kabihizi J, Murangwa A, Serumondo J, Makuza JD, Nsanzimana S, Muvunyi CM, Mukabatsinda C, Musabeyezu E, Camus G, Grant PM, Kateera F. Safety and efficacy of sofosbuvir-velpatasvir-voxilaprevir for re-treatment of chronic hepatitis C virus infection in patients with previous direct-acting antiviral treatment failure in Rwanda (SHARED-3): a single-arm trial. Lancet Gastroenterol Hepatol. 2022 Jun;7(6):542-551. doi: 10.1016/S2468-1253(21)00399-X. Epub 2022 Mar 3.