Simplified Antiviral Treatment Strategy for Hepatitis C in Ukraine

NCT04038320 | Completed FDA Drug

• 1 other identifier: EQUIPHCV02-UKR
• Study Type: observational
• Target: 868
• Locations: 1 country
• Sites: 2

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.

Conditions

Hepatitis C Virus

Keywords

Hepatitis C Virus; HIV; Key Population

Outcome Measures

Primary Outcomes (2)

• 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

  The average cost to the provider per patient achieving SVR-12 will be estimated, as will the average cost per other outcomes achieved, such as per patient screened and per patient remaining in care by other specified endpoints, stratified by HIV status and by any other important patient or site characteristics that are identified as drivers of cost. The investigators will also estimate the average cost to "produce" a successful outcome (SVR-12), which is the ratio of total costs for the intervention for the entire sample enrolled to the number of patients achieving the primary outcome. This latter estimate captures the costs incurred for patients who do not have successful outcomes and thus relates resource utilization to health outcomes.

  Two years. This will be after data on Viral load response is complete.

• Sustained Viral Response

  This will be the main treatment outcome of all patients initiated on treatment. Baseline viral load is done at entry with treatment initiated for those positive and eligible. Patients initiated on treatment will be assessed for viral load response at 24 weeks ( 12 weeks post treatment). This will also help in development of a Care cascade model for HCV testing, treatment and SVR12 in key populations co-infected with HIV/HCV, HIV/HCV/HBV, HBV/HCV and HCV mono-infected.

  24 weeks ( 12 weeks post treatment)

Secondary Outcomes (5)

• HCV genotype

  At baseline

• HCV subtype

  Baseline

• Validity of Cepheid Gene-Xpert in monitoring SVR12

  Testing done and baseline and 24 weeks

• HIV viral load among HCV/HIV co-infected patients

  HIV Viral load at 24 weeks ( 12 weeks post HCV treatment)

• Reliability of Cepheid Gene-Xpert in monitoring SVR12

  Testing done and baseline and 24 weeks

Study Arms (1)

HCV infected patients

All HCV infected confirmed by HCV RNA,

Drug: Sofosbuvir/ledipasvir (SOF/LDV)

Interventions

Sofosbuvir/ledipasvir (SOF/LDV) DRUG

SOF/LDV (400mg/90mg) orally once daily with or without food in the morning and will receive treatment for a duration of 12 weeks. In addition, Ribavirin weight-based (1000 mg for patients \<75 kg and 1200 mg for those ≥75 kg) administered orally in two divided doses with food for Genotype 3 patients.

HCV infected patients

Eligibility Criteria

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

You may qualify if:

• Ability and willingness of participant to provide informed consent.
• 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
• Men and women age 18 years.
• 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.
• Allowed HCV treatment history:
• 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.
• HCV treatment experienced with interferon with or without ribavirin only (no prior DAA treatment, although they will be followed).
• 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.
• HIV-1 infection status must be documented as either absent or present, as defined below:
• 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.
• 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.
• HIV-1 infection confirmed by medical documentation as participant is registered in care at AIDS Center and receiving or preparing to initiate ARV treatment.
• Participants who are assigned to receive ribavirin as part of the treatment protocol must have haemoglobin ≥110 g/L
• 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.
• 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.

You may not qualify if:

• 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.
• Breastfeeding or pregnancy. Pregnant or breastfeeding woman will be documented and provided access to HCV treatment after resolution of pregnancy and breastfeeding.
• Known allergy/sensitivity or any hypersensitivity to components of drug(s) or their formulation.
• 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.
• 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
• Prior treatment with any HCV Direct Acting Agents (DAA).

Sponsors & Collaborators

• Right to Care: lead
• All Ukrainian Network of PLHA: collaborator
• Public Health Center of MOH Ukraine: collaborator
• Alliance for the Public's Health: collaborator
• Boston University: collaborator
• University of California, Los Angeles: collaborator

Study Sites (2)

Clinic of the Institute of Epidemiology and Infectious Diseases, National Academy of Medical Sciences of Ukraine

Kiev, Ukraine

Location

Kyiv City Clinical Hospital #5

Kyiv, Ukraine

Location

Related Publications (6)

• Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014 Nov;61(1 Suppl):S45-57. doi: 10.1016/j.jhep.2014.07.027. Epub 2014 Jul 30.

  PMID: 25086286 RESULT

• 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.

  PMID: 23172780 RESULT

• 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.

  PMID: 25271370 RESULT

• 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.

  PMID: 25252742 RESULT

• 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.

  PMID: 26571066 RESULT

• 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.

  PMID: 26261007 RESULT

Related Links

• Over 5% of Ukrainians are infected with hepatitis C. 2016
• EASL Recommendations on Treatment of Hepatitis C 2016. 2016

Biospecimen

Retention: SAMPLES WITHOUT DNA

Dry blood spots(DBS) collected at baseline, 4, 8, 12 and 24 weeks for viral load and resistance testing will be determined where indicated.

MeSH Terms

Conditions

Hepatitis C

Interventions

Sofosbuvir; ledipasvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Officials

• Ian Sanne, MBBCH, FRCP

  Right to Care

  STUDY CHAIR

• Svetlana Antonyak, MD

  Hepatitis and HIV-infection of Institute of Epidemiology and Infectious Diseases of L.V. Gromashevskiy of NAMS of Ukraine

  PRINCIPAL INVESTIGATOR

• Tetiana Benard, MA

  Right to Care, Ukraine

  PRINCIPAL INVESTIGATOR

• Charles Chasela, PhD

  Right to Care

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2018
• First Posted: July 30, 2019
• Study Start: March 26, 2018
• Primary Completion: March 30, 2019
• Study Completion: June 30, 2019
• Last Updated: July 30, 2019

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: One to two years after completion of the study
• Access Criteria: Based on a concept submitted, reviewed and accepted

Locations

UA (2)