Clinical trial NCT04038320: Simplified Antiviral Treatment Strategy for Hepatitis C in Ukraine
Official title: Demonstration Project on Assessment of Simplified Antiviral Treatment Strategy for Hepatitis C in Ukraine
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis C Virus
Keywords: Hepatitis C Virus
HIV
Key Population
Lead sponsor: Right to Care
Sponsor class: OTHER
Collaborators: name: All Ukrainian Network of PLHA
name: Public Health Center of MOH Ukraine
name: Alliance for the Public's Health
name: Boston University
name: University of California, Los Angeles
First posted: 2019-07-30
Enrollment: 868
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 study population are HCV treatment naïve or experienced (pegylated interferon \[PegIFN\] and ribavirin \[RBV\] only), HCV-infected with genotype 1, 2, 3, 4, 5 or 6, men and women aged 18 years or older, with or without HIV-1 co-infection, representatives of key populations (PWID, CSW, MSM) and their partners. Participants with compensated cirrhosis or Hepatitis B will be eligible for HCV treatment. Patients with decompensated liver cirrhosis or prior treatment with HCV DAAs will not be eligible for treatment. HCV-infected patients who are not eligible for HCV treatment will be eligible for an observation arm.

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 in Ukraine.

Detailed description: Affected populations will be screened for HCV and HIV and those HCV positive treated with direct with direct acting anti-HCV agents (DAAs), a fixed-dose combination of sofosbuvir/ledipasvir (SOF/LDV) 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 800 patients enrolled on treatment will be followed up at 4, 8, 12 and 24 weeks when Sustained Viral Response (SVR) 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 (GCP). In addition to assessing cost outcomes, the project will assess HCV treatment efficacy in terms of SVR at 12 weeks after end of treatment ( defined as undetected HCV RNA or less than lower limit of detection), compare the cost of low cost viral assay platforms to standard of care, assess rates of ART initiation and virologic suppression of HIV-infected persons within the simplified HCV treatment model and impact of HIV co-infection in participants on the HCV treatment outcome of SVR12. The project will be conducted at 2 treatment sites in Kiev.

Eligibility criteria: Inclusion Criteria:

1. Ability and willingness of participant to provide informed consent.
2. Attribution to one of the key population groups: People Who Inject Drugs (PWID), medication assisted treatment (MAT) participants, Commercial Sex Workers (CSW) or Men Having Sex with Men (MSM). Documentation of attribution to one of the key population groups will be done through applying Case Reporting Form "Risks Assessment" and "Substance Use and Alcohol Consumption". Additionally, medical record of substance use can be collected
3. Men and women age 18 years.
4. 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. If no medical records on HCV infection are available, HCV infection must be confirmed by a detectable HCV RNA PCR prior to project entry.
5. 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, although they will be followed).
6. 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 hepatitis B surface antigen (HBsAg+) must be on an active HBV regimen at study entry.
7. 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 and confirmed by a second antibody test by a method other than the initial rapid HIV and/or ELISA, or by HIV-1 antigen or plasma HIV-1 RNA viral load.

      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.
8. Participants who are assigned to receive ribavirin as part of the treatment protocol must have haemoglobin ≥110 g/L
9. For females of reproductive potential, a negative urine pregnancy test (urine -HCG with a sensitivity of \<25 mIU/mL) within 48 hours prior to project entry 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.

Note: Acceptable contraception/birth control for this project includes one of the following methods:

* condoms (male or female) with a spermicide
* diaphragm or cervical cap with spermicide
* hormonally impregnated intrauterine device (IUD)
* non-hormonally impregnated IUD in conjunction with spermicide
* Hormone-based therapy

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). For Child's cirrhosis severity calculator on the following link can be used: http://www.hepatitisc.uw.edu/page/clinical-calculators/ctp . Patients with decompensated cirrhosis and advanced liver disease will not be included to the treatment program, but they will remain under observation and will receive medical care within routine medical practice of the healthcare facility in such clinical cases.
2. Breastfeeding or pregnancy. Pregnant or breastfeeding woman will be documented and provided access to HCV treatment after resolution of pregnancy and breastfeeding.
3. Known allergy/sensitivity or any hypersensitivity to components of drug(s) or their formulation.
4. Active tuberculosis (TB) infection. Given the high TB prevalence in Ukraine, every candidate should be screened for TB signs/symptoms with further medical evaluation for active TB as indicated. In the case of proven active TB infection, the participant is ineligible for HCV treatment (due to the adverse drug interaction of SOF/LDV and rifampicin) but will be followed and offered enrolment when they complete treatment with rifampicin.
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/LDV is contraindicated (https://www.mdcalc.com/mdrd-gfr-equation). The participant may be rescreened if the renal function improves. Patients with worse renal impairment will not be treated but will be followed and will recive medical aid within routine medical practice of the healthcare facility where project is implemented
6. Prior treatment with any HCV Direct Acting Agents (DAA).

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: Sustained Viral Response
timeFrame: 24 weeks ( 12 weeks post treatment)
Secondary outcomes:
measure: HCV genotype
timeFrame: At baseline
measure: HCV subtype
timeFrame: Baseline
measure: Validity of Cepheid Gene-Xpert in monitoring SVR12
timeFrame: Testing done and 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)
measure: Reliability of Cepheid Gene-Xpert in monitoring SVR12
timeFrame: Testing done and baseline and 24 weeks
Other outcomes:
Locations:
city: Kiev
country: Ukraine
facility: Clinic of the Institute of Epidemiology and Infectious Diseases, National Academy of Medical Sciences of Ukraine
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #5
Study officials:
affiliation: Right to Care
name: Ian Sanne, MBBCH, FRCP
role: STUDY_CHAIR
affiliation: Hepatitis and HIV-infection of Institute of Epidemiology and Infectious Diseases of L.V. Gromashevskiy of NAMS of Ukraine
name: Svetlana Antonyak, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Right to Care, Ukraine
name: Tetiana Benard, MA
role: PRINCIPAL_INVESTIGATOR
affiliation: Right to Care
name: Charles Chasela, PhD
role: STUDY_DIRECTOR
References:
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citation: Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013 Apr;57(4):1333-42. doi: 10.1002/hep.26141. Epub 2013 Feb 4.
citation: Jaenisch T, Junghanss T, Wills B, Brady OJ, Eckerle I, Farlow A, Hay SI, McCall PJ, Messina JP, Ofula V, Sall AA, Sakuntabhai A, Velayudhan R, Wint GR, Zeller H, Margolis HS, Sankoh O; Dengue in Africa Study Group. Dengue expansion in Africa-not recognized or not happening? Emerg Infect Dis. 2014 Oct;20(10):e140487. doi: 10.3201/eid2010.140487.
citation: Lazarus JV, Sperle I, Maticic M, Wiessing L. A systematic review of Hepatitis C virus treatment uptake among people who inject drugs in the European Region. BMC Infect Dis. 2014;14 Suppl 6(Suppl 6):S16. doi: 10.1186/1471-2334-14-S6-S16. Epub 2014 Sep 19.
citation: Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S; ASTRAL-1 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med. 2015 Dec 31;373(27):2599-607. doi: 10.1056/NEJMoa1512610. Epub 2015 Nov 16.
citation: Gane EJ, Hyland RH, An D, Svarovskaia E, Pang PS, Brainard D, Stedman CA. Efficacy of ledipasvir and sofosbuvir, with or without ribavirin, for 12 weeks in patients with HCV genotype 3 or 6 infection. Gastroenterology. 2015 Nov;149(6):1454-1461.e1. doi: 10.1053/j.gastro.2015.07.063. Epub 2015 Aug 7.