Clinical trial NCT02601976: Evaluation of Unipeg® for Response and Ongoing Safety in Pakistani Population
Official title: Response Evaluation of Peginterferon Alfa-2a 180µg 20kDa (Unipeg®) Plus Ribavirin (Ribazole®) in Treatment naïve Pakistani Population With Chronic Hepatitis C Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C
Keywords: PegInterferon alpha-2a
Ribavirin
Hepatitis C Virus
Sustained Virological Response
End of Treatment Response
Unipeg
Ribazole
Lead sponsor: Getz Pharma
Sponsor class: INDUSTRY
Collaborators: name: Dimension Research
First posted: 2015-11-11
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Hepatitis C is a global problem, prevalent in developed as well as in the developing countries. New treatment regimens using PegInterferon in combination with ribavirin has led to improved sustained viral response rates for some genotypes. A single arm, open labeled, multicentre trial was conducted to evaluate the response rate and safety of PegInterferon alfa-2a (Unipeg®) plus ribavirin (Ribazole®) for the treatment of patients with chronic hepatitis C infection. RVR at 4 weeks, ETR at 24 weeks for genotype 3 and at 48 weeks for genotype 1 patients and SVR was determined at 24 weeks after completion of treatment. Quality of life at baseline and at follow-up visits were determined using SF-36.

Detailed description: A multicenter, phase IV, open labeled, single arm study was conducted. Total 110 patients were screened for recruitment. Out of which 67 subjects met the inclusion criteria, 3 failed to give the informed consent and were excluded. The final sample size of the study was 64 patients. The duration of study was August 2010 to September 2013. Peginterferon alfa-2a 180µg 20kDa (Unipeg®) solution for injection was administered as single dose sub-cutaneous once weekly for 24 weeks to patients with genotype 3 and 48 weeks in patients with genotype 1 at the site of recruitment. Ribavirin (Ribazole) orally were given in divided daily dose according to body weight-based dosing recommendations (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg). Quality of life related Physical Component Score (PCS) \& Mental Component Score (MCS) were measured through Health-Related Quality of Life (HRQOL) Questionnaire (SF-36). The SF-36 questionnaire was completed for all patients during their evaluations before treatment, at 4 weeks, at the end of treatment and at 24 weeks after completion of treatment.

Eligibility criteria: Inclusion Criteria:

1. Written Informed consent
2. Treatment naïve patients
3. Serological evidence of hepatitis C infection by an anti-HCV antibody test
4. HCV positive by PCR
5. Genotype 1,2 and 3
6. BMI 20-28
7. Participants were the resident of city where he /she enrolled at their respective centre
8. No evidence of liver cirrhosis
9. No other significant hepatic or systemic disease
10. No evidence of hepatic encephalopathy
11. Normal thyroid functions (By testing TSH)
12. Adequate bone marrow, liver and renal functions test

    * Hematology: ANC≥1,000/mm3, Platelet count ≥100,000 mm3, Hemoglobin≥11.0g/dl in female and ≥ 12.0 g/dl in male
    * Blood Chemistry: Total Bilirubin≤2.0mg/dl, AST and ALT \<3 times normal
    * Creatinine Clearance \>50 ml/min
    * Proteinuria: ≤ 0.5 g per 24h.
    * Prothrombin Time or partial-thromboplastin time if ≤1.5 times the upper limit of the normal range.

Exclusion Criteria:

1. Unable to give consent
2. Prior treatment for Hepatitis C
3. Co-infection with HBV and HCV
4. Obesity
5. Iron overload
6. Other Genotypes e.g. 4, 5, 6 with their sub-types
7. Pregnant and lactating women
8. History of medical condition associated with chronic liver disease other than CHC (e.g. hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposure)
9. Uncontrolled Hypertension
10. Uncontrolled Diabetes
11. Severe Depression
12. Clinically significant cardio-vascular disease
13. Symptomatic peripheral vascular disease
14. Oral or parenteral anticoagulants or anti platelet agents
15. History of systemic anti-viral therapy at least three months prior to first dose of study medication

Primary outcomes:
measure: Number of Participants With Sustained Virological Response (SVR)
timeFrame: Post treatment Week 24
measure: Number of Participants With End Treatment Response
timeFrame: Upto 48 weeks
Secondary outcomes:
measure: Number of Participants Who Reported Adverse Events
timeFrame: Upto 48 weeks
Other outcomes:
measure: Number of Participants With Rapid Virological Response (RVR)
timeFrame: 4 weeks
measure: Mean of Physical Component Score & Mental Component Score to Determine Quality of Life
timeFrame: Upto 48 weeks
Locations:
Study officials:
affiliation: Getz Pharma Pakistan
name: Dr. Khawar Mehdi, MD
role: STUDY_DIRECTOR
References:
citation: Chander G, Sulkowski MS, Jenckes MW, Torbenson MS, Herlong HF, Bass EB, Gebo KA. Treatment of chronic hepatitis C: a systematic review. Hepatology. 2002 Nov;36(5 Suppl 1):S135-44. doi: 10.1053/jhep.2002.37146.
citation: Abbas Z, Jeswani NL, Kakepoto GN, Islam M, Mehdi K, Jafri W. Prevalence and mode of spread of hepatitis B and C in rural Sindh, Pakistan. Trop Gastroenterol. 2008 Oct-Dec;29(4):210-6.
citation: Ali SA, Donahue RM, Qureshi H, Vermund SH. Hepatitis B and hepatitis C in Pakistan: prevalence and risk factors. Int J Infect Dis. 2009 Jan;13(1):9-19. doi: 10.1016/j.ijid.2008.06.019. Epub 2008 Oct 2.
citation: European Association for Study of Liver. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol. 2015 Jul;63(1):199-236. doi: 10.1016/j.jhep.2015.03.025. Epub 2015 Apr 21. No abstract available.
citation: Idrees M, Riazuddin S. Frequency distribution of hepatitis C virus genotypes in different geographical regions of Pakistan and their possible routes of transmission. BMC Infect Dis. 2008 May 23;8:69. doi: 10.1186/1471-2334-8-69.
citation: Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM; PEGASYS International Study Group. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004 Mar 2;140(5):346-55. doi: 10.7326/0003-4819-140-5-200403020-00010.
citation: Ahmad, T., R. Ahsan, and G. Saba. Evaluation of Safety and Pharmacokinetic Behavior of Unipeg® in Healthy Human Volunteers. Journal of Pharmacy and Nutrition Sciences 2014;4.3:220-227