Simplifying HCV Treatment in Rwanda for Elsewhere in the Developing World: Pangenotypic and Retreatment Study (SHARED3)

NCT03888729 | Unknown Phase 4 DMC FDA Drug

• 1 other identifier: PartnersIH
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C, Chronic

Keywords

Hepatitis C; direct-acting antiviral; Rwanda

Outcome Measures

Primary Outcomes (2)

• Proportion of participants with sustained viral response 12 weeks after discontinuation of study treatment (SVR12)

  Antiviral efficacy of SOF/VEL FDC and SOF/VEL/VOX 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 (week 24)

• 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

  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

  After study completion (week 24)

Secondary Outcomes (5)

• Proportion of participants by HCV genotype subtypes with SVR12 after completing treatment with SOF/VEL FDC and SOF/VEL/VOX FDC

  After study completion (week 24)

• Adherence to SOF/VEL FDC and SOF/VEL/VOX FDC

  After study completion (week 24)

• 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

  After study completion (week 24)

• Proportion of HIV co-infected subjects that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment

  After study completion (week 24)

• Effect of SOF/VEL FDC and SOF/VEL/VOX FDC and SVR12 on quality of life

  After study completion (week 24)

Study Arms (2)

HCV treatment-naïve participants

EXPERIMENTAL

HCV-infected individuals naïve to DAA therapy regimen; in this group we consider also HCV-infected individuals who have failed interferon-based therapy. Sofosbubir/velpatasvir (SOF/VEL) will be administered once daily for 12 weeks to eligible HCV treatment-naïve participants.

Drug: sofosbubir/velpatasvir

HCV treatment-experienced participants

EXPERIMENTAL

HCV treatment-experienced participants, i.e.HCV-infected individuals with a history of virologic failure to SOF/LDV or other DAA-containing regimen. Sofosbubir/velpatasvir /voxilaprevir (SOF/VEL/VOX) will be administered once daily for 12 weeks to eligible HCV treatment-experienced participants

Drug: sofosbubir/velpatasvir/voxilaprevir

Interventions

sofosbubir/velpatasvir DRUG

SOF/VEL (400 mg/100 mg) FDC once daily

Also known as: Epclusa

HCV treatment-naïve participants

sofosbubir/velpatasvir/voxilaprevir DRUG

SOF/VEL/VOX (400 mg/100 mg/100 mg) FDC once daily

Also known as: Vosevi

HCV treatment-experienced participants

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Partners in Health: lead

Study Sites (1)

Rwanda Military Hospital

Kigali, Rwanda

RECRUITING

Related Publications (3)

• 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.

  PMID: 30552056 RESULT

• 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.

  PMID: 35248213 DERIVED

• 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.

  PMID: 35248212 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

velpatasvir; sofosbuvir-velpatasvir drug combination; sofosbuvir velpatasvir voxilaprevir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Neil Gupta, MD, MPH

  Partners In Health; Brigham and Women's Hospital; Harvard Medical School

  PRINCIPAL INVESTIGATOR

• Fredrick Kateera, MD, PhD

  Partners In Health/Inshuti Mu Buzima - Rwanda

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabienne Shumbusho, MD

CONTACT

+250788559065; Fshumbusho@pih.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: March 25, 2019
• Study Start: August 26, 2019
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2020
• Last Updated: September 11, 2019

Record last verified: 2019-09

Locations

RW (1)