Clinical trial NCT03579576: Simplified Antiviral Treatment Strategy for Hepatitis C in Myanmar
Official title: Demonstration Project on Assessment of Simplified Antiviral Treatment Strategy for Hepatitis C in Myanmar
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis C
Hepatitis B
HIV Infections
Keywords: PWID
MSM
HCV
HIV
Lead sponsor: Right to Care
Sponsor class: OTHER
Collaborators: name: Community Partners International
name: Myanmar Liver Foundation
name: Boston University
name: University of California, Los Angeles
name: Ministry of Health and Sports, Myanmar
First posted: 2018-07-06
Enrollment: 803
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The target population are key population including Female Sex Workers, Men who have sex with men and People Who Use InjecaAll HCV-infected men and women aged 18 years or older. The study population eligible for HCV treatment will be HCV treatment naïve or experienced (pegylated interferon \[PegIFN\] and ribavirin \[RBV\] only), HCV-infected men and women aged 18 years or older with HCV genotype 1, 2, 3, 4, 5 or 6, with or without HIV-1 co-infection. Participants with compensated cirrhosis (Child-Pugh Class A) and hepatitis B infection will be eligible for HCV treatment. Patients with decompensated liver cirrhosis (Child-Pugh Class B or C) or prior treatment with HCV DAAs will not be eligible for treatment.

Brief summary: The project will evaluate cost and treatment outcomes of a simplified hepatitis C virus (HCV) testing, treatment and care model integrated with HIV testing and treatment among key affected populations including people who inject drugs (PWID) in Myanmar.

Detailed description: Affected populations will be screened for HCV and HIV and treated with direct a fixed-dose combination of sofosbuvir 400 mg/velpatasvir 100 mg (SOF/VEL) orally once daily for 12 weeks with or without weight-based ribavirin. Before and after completion of the treatment course viral load assessments will be undertaken using low-cost laboratory monitoring for comparison to standard HCV viral load measurement. Up to 800 patients enrolled on treatment will be followed up at 4, 8, 12 and 24 weeks when Sustained Viral Load ( SVL) will be determined. Safety monitoring will be undertaken at applicable visits for those on Ribavirin and all adverse events will be reported based on Good Clinical Practice. In addition to assessing to assessing cost outcomes, the project will assess HCV treatment efficacy in terms of sustained virologic response at 12 weeks after end of HCV treatment (defined as undetected HCV RNA or less than lower limit of detection), compare the cost of low cost HCV viral assay platforms to standard of care, assess rates of ART initiation and virologic suppression of HIV-infected persons within the simplified HCV testing and treatment model and impact of HIV co-infection in participants on the HCV treatment outcome of sustained virologic response (SVR12). The project will be conducted 3 treatment sites in Yangon, Mandalay, and Kachin state in Myanmar.

Eligibility criteria: Inclusion Criteria:

1. Ability and willingness of participant to provide informed consent.
2. Men and women age 18 years.
3. Active HCV infection as defined by detectable serum or plasma HCV RNA at any time prior to study entry. Documentation may be obtained from medical records if available. NOTE: If no medical records on HCV infection are available, active HCV infection must be confirmed by a detectable HCV RNA PCR prior to project entry.
4. Allowed HCV treatment history:

   1. HCV treatment naïve defined as not having been previously treated for Hepatitis C infection with any medications approved for the treatment of HCV in any country.
   2. HCV treatment experienced with interferon with or without ribavirin only (no prior DAA treatment).
5. Chronic Hepatitis B status must be documented by hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and hepatitis B core antibody (HBcAb) testing. Participants with positive HBsAg must be already on an active HBV regimen at study entry.
6. HIV-1 infection status must be documented as either absent or present, as defined below:

   1. Absence of HIV-1 infection, as documented by rapid HIV test or HIV-1 enzyme immunoassay (ELISA) test kit, within 60 days prior to entry.

      OR
   2. Presence of HIV-1 infection, documented by rapid HIV test or HIV-1 ELISA test kit at any time prior to entry.

      OR
   3. HIV-1 infection confirmed by medical documentation as participant is registered in care at AIDS Center and receiving or preparing to initiate ARV treatment.
7. HIV co-infected participants taking ART or planning to initiate ART, should be:

   1. Tolerating ART for at least 2 weeks without signs of needing to modify or discontinue the ART regimen before initiating HCV treatment.

      AND
   2. The ART regimen must be a regimen that can be co-administered with SOF/VEL.
8. Participants who are assigned to receive ribavirin as part of the treatment protocol must have hemoglobin ≥11.0 g/dL
9. For females of reproductive potential who will receive ribavirin, a negative urine pregnancy test (urine -HCG with a sensitivity of \<25 mIU/mL) within 48 hours prior to project entry (HCV treatment initiation) must be documented.
10. Male and female participants who are able to impregnate or become pregnant (ie, of reproductive potential) and are participating in sexual activity that could lead to pregnancy must agree to practice contraception/birth control as indicated below or agree to not participate in a conception process while on treatment with ribavirin through at least 12 weeks post-treatment.
11. Life expectancy \>12 months, in the opinion of the site investigator

Exclusion Criteria:

1. Child-Pugh Score corresponding to Class B or C (decompensated cirrhosis). This requires assessment for encephalopathy and ascites, as well as measurement of serum bilirubin, albumin, and international normalized ratio (prothrombin time).
2. Breastfeeding or pregnancy if patient will be receiving ribavirin.
3. Known allergy/sensitivity or any hypersensitivity to components of drug(s) or their formulation.
4. Acute tuberculosis (TB) infection. They will be followed and offered enrolment when they complete TB treatment.
5. Renal impairment defined as estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73m2 or end-stage renal disease receiving dialysis as treatment with SOF/VEL is contraindicated (https://www.mdcalc.com/mdrd-gfr-equation).
6. Unwilling to provide informed consent for participation in the project.
7. Prior treatment with any HCV Direct Acting Agents (DAA).
8. Unable or unwilling to adhere to the HCV treatment course and monitoring in the opinion of the investigator.

Primary outcomes:
measure: Estimated cost of HCV screening per patient screened and per case identified and the cost per successfully treated patient for HCV mono-infected and co-infected participants
timeFrame: Two years. This will be after data on Viral load response is complete.
measure: Overall Sustained Viral load response (SVR12) across all groups of HCV genotype, fibrosis stage, HIV and HBV co-infection.
timeFrame: 24 weeks ( 12 weeks post treatment)
Secondary outcomes:
measure: HCV genotype and subtype
timeFrame: At baseline
measure: Validity and reliability of Cepheid GeneXpert in monitoring SVR12
timeFrame: Testing done at baseline and 24 weeks
measure: HIV Viral load among HCV/HIV co-infected patients
timeFrame: HIV Viral load at 24 weeks ( 12 weeks post HCV treatment)
Other outcomes:
Locations:
city: Kāchen
country: Myanmar
facility: Waimaw
state: Kachin
city: Mandalay
country: Myanmar
facility: Myanmar Liver Foundation Clinic
city: Yangon
country: Myanmar
facility: Myanmar Liver Foundation Charity Clinic
Study officials:
affiliation: Right to Care
name: Ian Sanne, MBBCH,FRCP
role: STUDY_CHAIR
affiliation: Myanmar Liver Foundation
name: Khin Pyone Khi, MBBS,FRCP,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Right to Care
name: Charles Chasela, PhD
role: STUDY_DIRECTOR
References: