Back to resultsSimplifying HCV Treatment in Rwanda for Elsewhere in the Developing World: Pangenotypic and Retreatment Study (SHARED3) (SHARED3)
Primary Purpose
Hepatitis C, Chronic
Status
Unknown status
Phase
Phase 4
Locations
Rwanda
Study Type
Interventional
Intervention
sofosbubir/velpatasvir
sofosbubir/velpatasvir/voxilaprevir
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic focused on measuring Hepatitis C, direct-acting antiviral, Rwanda
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
Sites / Locations
- Rwanda Military HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
HCV treatment-naïve participants
HCV treatment-experienced participants
Arm Description
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.
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
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
Proportion of participants by HCV genotype subtypes with SVR12 after completing treatment with SOF/VEL FDC and SOF/VEL/VOX FDC
Proportion of participants by HCV genotype 4 subtype with SVR12 after completing the study treatment with SOF/VEL FDC and SOF/VEL/VOX FDC
Adherence to SOF/VEL FDC and SOF/VEL/VOX FDC
Proportion of participants with adequate adherence to SOF/VEL FDC and SOF/VEL/VOX FDC measured by pill count >90% of pills taken
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
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
Proportion of HIV co-infected subjects that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment
Proportion of HIV co-infected subjects that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment, with HIV-1 RNA test performed at completion of the study treatment (week 12)
Effect of SOF/VEL FDC and SOF/VEL/VOX FDC and SVR12 on quality of life
Effect of SOF/VEL FDC and SOF/VEL/VOX FDC and SVR12 on quality of life, using the MOS HIV questionnaire, with proportion of patients showing significant improvement on physical quality of life and mental quality of life from pre- to post- treatment
Full Information
NCT ID
NCT03888729
First Posted
February 15, 2019
Last Updated
September 10, 2019
Sponsor
Partners in Health
1. Study Identification
Unique Protocol Identification Number
NCT03888729
Brief Title
Simplifying HCV Treatment in Rwanda for Elsewhere in the Developing World: Pangenotypic and Retreatment Study (SHARED3)
Acronym
SHARED3
Official Title
Simplifying Hepatitis C Antiviral Therapy in Rwanda for Elsewhere in the Developing World: Pangenotypic and Retreatment Study (SHARED3)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Unknown status
Study Start Date
August 26, 2019 (Actual)
Primary Completion Date
March 2020 (Anticipated)
Study Completion Date
March 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Partners in Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
Keywords
Hepatitis C, direct-acting antiviral, Rwanda
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HCV treatment-naïve participants
Arm Type
Experimental
Arm Description
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.
Arm Title
HCV treatment-experienced participants
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
sofosbubir/velpatasvir
Other Intervention Name(s)
Epclusa
Intervention Description
SOF/VEL (400 mg/100 mg) FDC once daily
Intervention Type
Drug
Intervention Name(s)
sofosbubir/velpatasvir/voxilaprevir
Other Intervention Name(s)
Vosevi
Intervention Description
SOF/VEL/VOX (400 mg/100 mg/100 mg) FDC once daily
Primary Outcome Measure Information:
Title
Proportion of participants with sustained viral response 12 weeks after discontinuation of study treatment (SVR12)
Description
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
Time Frame
After study completion (week 24)
Title
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
Description
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
Time Frame
After study completion (week 24)
Secondary Outcome Measure Information:
Title
Proportion of participants by HCV genotype subtypes with SVR12 after completing treatment with SOF/VEL FDC and SOF/VEL/VOX FDC
Description
Proportion of participants by HCV genotype 4 subtype with SVR12 after completing the study treatment with SOF/VEL FDC and SOF/VEL/VOX FDC
Time Frame
After study completion (week 24)
Title
Adherence to SOF/VEL FDC and SOF/VEL/VOX FDC
Description
Proportion of participants with adequate adherence to SOF/VEL FDC and SOF/VEL/VOX FDC measured by pill count >90% of pills taken
Time Frame
After study completion (week 24)
Title
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
Description
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
Time Frame
After study completion (week 24)
Title
Proportion of HIV co-infected subjects that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment
Description
Proportion of HIV co-infected subjects that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment, with HIV-1 RNA test performed at completion of the study treatment (week 12)
Time Frame
After study completion (week 24)
Title
Effect of SOF/VEL FDC and SOF/VEL/VOX FDC and SVR12 on quality of life
Description
Effect of SOF/VEL FDC and SOF/VEL/VOX FDC and SVR12 on quality of life, using the MOS HIV questionnaire, with proportion of patients showing significant improvement on physical quality of life and mental quality of life from pre- to post- treatment
Time Frame
After study completion (week 24)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fabienne Shumbusho, MD
Phone
+250788559065
Email
Fshumbusho@pih.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neil Gupta, MD, MPH
Organizational Affiliation
Partners In Health; Brigham and Women's Hospital; Harvard Medical School
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fredrick Kateera, MD, PhD
Organizational Affiliation
Partners In Health/Inshuti Mu Buzima - Rwanda
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rwanda Military Hospital
City
Kigali
Country
Rwanda
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabienne Shumbusho
Phone
+250788559065
Ext
+250788559065
Email
Fshumbusho@pih.org
12. IPD Sharing Statement
Citations:
PubMed Identifier
30552056
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.
Results Reference
result
PubMed Identifier
35248213
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.
Results Reference
derived
PubMed Identifier
35248212
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.
Results Reference
derived
Learn more about this trial
Simplifying HCV Treatment in Rwanda for Elsewhere in the Developing World: Pangenotypic and Retreatment Study (SHARED3)
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