To Study the Effect of Adding on Pegylated Interferon (PEG-INF) Therapy for Patients Diagnosed With Chronic Hepatitis B

Hepatitis B Clinical Trial

— RC14/055  

Official title:

Randomized, Multicenter, Open -Label Clinical Trial to Study the Effect of Adding on Pegylated Interferon Therapy for Patients Diagnosed With Chronic Hepatitis B Showing Maintained Response While Receiving Ongoing Nucleotide Analogues

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02982837
• Other study ID #: PDU15001
• Status: Recruiting
• Phase: Phase 4
• First received: August 7, 2016
• Last updated: March 8, 2018
• Start date: March 2015
• Est. completion date: May 2019

Study information

• Verified date: January 2018
• Source: King Abdullah International Medical Research Center
• Contact: Abduljaleel Alalwan, MD
• Phone: 801 111
• Email: alwana[@]ngha.med.sa
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To assess whether PEG-INF (Peglyated - interferon) Add-on therapy in patients of CHB who have achieved a maintained viral suppression (HBV DNA PCR( polymerase chain reaction) <200 for last 3-6 month) with NA's can result in increased rate of HBV infection eradication (HbsAg is undetectable by serological blood testing with or without seroconversion to HBs antibody).

Description:

Hepatitis B virus (HBV) infection remains a global health care problem with more than one third of world's population having serological evidence of been exposed to the virus and about 5% of global population ( 350-400 million) being chronically infected. About 15-40% of Patients with chronic hepatitis B (CHB) infection develop complications of liver cirrhosis, liver failure and hepatocellular carcinoma(HCC) in their life time , resulting in an estimated of 500,000 to 1.2 million deaths each year. In Saudi Arabia, chronic hepatitis B remains a serious medical problem, despite the implementation of mandatory HBV vaccination of children since 1989. According to a recent study conducted in Saudi hospital, HBV accounts for 49% of the hepatitis cases . Persistent viral replication is associated with disease progression to liver fibrosis, cirrhosis and development of HCC. Currently two classes of drugs are available for treatment of CHB namely immunomodulatory therapy (conventional & pegylated interferon (Pegasys) PEG-IFN) and nucleoside/nucleotide analogues(NA). Interferon(IFN)-α with its dual immunomodulatory and antiviral effects was the first drug (recombinant standard IFN- α) licensed for Chronic hepatitis B treatment in the 1990's followed by introduction of nucleos(t)ide analogues(NA) in 1998 that directly inhibit HBV polymerase and provide an effective on treatment maintained viral suppression . With the introduction of pegylated interferon- α (PEG-IFN) in 2005 that allows a convenient once a week dosing interval and of equal or superior treatment efficacy than conventional (IFN), the interferon based therapy has markedly improved its utility. Due to its predominant immunomodulatory effect peginterferon (PEG-IFN) offers the advantage of higher sustained off treatment response rate compared to NA thus allowing a finite duration of treatment. The NA act by directly inhibiting HBV polymerase resulting in effective on treatment maintained viral suppression (HBV DNA PCR <200 for last 3-6 month)). However, long term NA therapy has the problems of emergence of viral resistance, long -term safety, cost and patient compliance.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 214
• Est. completion date: May 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Adults =18 & < 70 years of both genders.

• CHB on NA's in maintained viral suppression (HBV DNA PCR <200 for last 3-6 month)

• Patients with measurable HBsAg quantitative levels

• Patients with any HBV genotypes.

• Patients with either CHB e Ag positive or eAg negative

• Patients who sign an informed consent for inclusion into the study.

• Patients with hepatitis Delta co-infection.

• only patients with a negative pregnancy test who are of child bearing potential and agree to utilize a strict birth control method will be enrolled

Exclusion Criteria:

• Patients with following characteristics will not be considered for the trial:

• Decompensated liver Cirrhosis

• HCV (hepatitis C virus) or HIV co infection.

• Autoimmune disorders like SLE (Systemic lupus erythematosus), RA (Rheumatoid Arthritis ), AIH (Autoimmune Hemolytic Anemia), ITP (Immune thrombocytopenic purpura), psoriasis etc.

• Untreated psychiatric conditions like depression and alcohol or drug abuse.

• Comorbid conditions like chronic renal failure or post renal/liver transplantation on immunosuppressive therapy.

• Complicated diabetes mellitus and advanced heart failure.

• Pregnancy or not willing to practice contraception.

• Known allergy to Interferons.

• Concomitant treatment with Telbivudine

• Evidence of portal hypertension by Biochemical (Low Platelets less than 100), imaging or UGI (upper gastrointestinal)endoscopy

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• PEG-IFN & Nucleos(t)tide analogues
Subjects who will be randomized to receive 180 Mcg/ week as an add-on Pegylated Interferon therapy a-2 A with their ongoing NUCLEOTIDE analogues for 48 weeks.
• Nucleos(t)tide analogues
Subjects will continue on the same dose of Nucleoside/nucleotide analogues as they started the study.

Locations

Country	Name	City	State
Saudi Arabia	King Abdulaziz Hospital	Jeddah
Saudi Arabia	King Abdulaziz Medical City	Jeddah
Saudi Arabia	King Abdulaziz Medical City	Riyadh

Sponsors (2)

Lead Sponsor	Collaborator
King Abdullah International Medical Research Center	Hoffmann-La Roche

Country where clinical trial is conducted

Saudi Arabia, 

References & Publications (13)

Al-Tawfiq JA, Anani A. Profile of viral hepatitis A, B, and C in a Saudi Arabian hospital. Med Sci Monit. 2008 Jan;14(1):CR52-56. — View Citation

Beasley RP. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer. 1988 May 15;61(10):1942-56. Review. — View Citation

Bosch FX, Ribes J, Cléries R, Díaz M. Epidemiology of hepatocellular carcinoma. Clin Liver Dis. 2005 May;9(2):191-211, v. Review. — View Citation

Chan HL, Tse CH, Mo F, Koh J, Wong VW, Wong GL, Lam Chan S, Yeo W, Sung JJ, Mok TS. High viral load and hepatitis B virus subgenotype ce are associated with increased risk of hepatocellular carcinoma. J Clin Oncol. 2008 Jan 10;26(2):177-82. doi: 10.1200/JCO.2007.13.2043. — View Citation

Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. — View Citation

Cooksley WG, Piratvisuth T, Lee SD, Mahachai V, Chao YC, Tanwandee T, Chutaputti A, Chang WY, Zahm FE, Pluck N. Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. J Viral Hepat. 2003 Jul;10(4):298-305. — View Citation

Goldstein ST, Zhou F, Hadler SC, Bell BP, Mast EE, Margolis HS. A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol. 2005 Dec;34(6):1329-39. Epub 2005 Oct 25. — View Citation

Lee A. Prevention of Helicobacter pylori infection. Scand J Gastroenterol Suppl. 1996;215:11-5. Review. — View Citation

Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009 Feb 14;373(9663):582-92. doi: 10.1016/S0140-6736(09)60207-5. — View Citation

Liaw YF, Leung N, Kao JH, Piratvisuth T, Gane E, Han KH, Guan R, Lau GK, Locarnini S; Chronic Hepatitis B Guideline Working Party of the Asian-Pacific Association for the Study of the Liver. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int. 2008 Sep;2(3):263-83. doi: 10.1007/s12072-008-9080-3. Epub 2008 May 10. — View Citation

Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007 Feb;45(2):507-39. Erratum in: Hepatology. 2007 Jun;45(6):1347. — View Citation

Memish ZA, Knawy BA, El-Saed A. Incidence trends of viral hepatitis A, B, and C seropositivity over eight years of surveillance in Saudi Arabia. Int J Infect Dis. 2010 Feb;14(2):e115-20. doi: 10.1016/j.ijid.2009.03.027. Epub 2009 Jun 21. — View Citation

Zoulim F, Locarnini S. Hepatitis B virus resistance to nucleos(t)ide analogues. Gastroenterology. 2009 Nov;137(5):1593-608.e1-2. doi: 10.1053/j.gastro.2009.08.063. Epub 2009 Sep 6. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The loss of HbsAg between groups (NA) group and NA +Peg_INF group assessed by HbsAg test	The loss of HbsAg between groups (NA) group and NA +Peg_INF group assessed by HbsAg test	48 weeks
Secondary	The seroconversion to HBs antibody between groups (NA) group and NA +Peg_INF group assessed by Hbe Ab test	The seroconversion to HBs antibody between groups (NA) group and NA +Peg_INF group assessed by Hbe Ab test	6 ,12 months & 48 weeks
Secondary	The HBeAg (Hepatitis B e-Antigen) loss in CHRONIC HBV eAg positive patient between groups (NA) group and NA +Peg_INF group assessed by HbeAg test	HBeAg loss in CHRONIC HBV eAg positive patient between groups (NA) group and NA +Peg_INF group assessed by HbeAg test	6,12 months & 48 weeks
Secondary	The conversion of HBeAg to HBe-antibody in CHRONIC HBV eAg (eAntigen) positive patient between groups (NA) group and NA +Peg_INF group assessed by HBe-antibody test	The conversion of HBeAg to HBe-antibody in CHRONIC HBV eAg positive patient between groups (NA) group and NA +Peg_INF group assessed by HBe-antibody test	6,12 months & 48 weeks
Secondary	The correlation between HBsAg ( Hepatitis B Surface Antigen) levels while on therapy at the a defined interval ie 8,12.24,36,48 weeks and rate of HBsAg loss at end of therapy assessed by measuring HBV s Ag during the period 8,12.24,36 and 48 weeks	The correlation between HBsAg levels while on therapy at the a defined interval ie 8,12.24,36,48 weeks and rate of HBsAg loss at end of therapy assessed by measuring HBV s Ag during that period 8,12.24,36 and 48 weeks	8,12,24 and 48 weeks
Secondary	The relationship between HBV genotype and HBsAg loss at the end of the study assessed by measuring HBV genotype only at base line and see if any particular genotype have more HBV sAg loss at the end of the study	The relationship between HBV genotype and HBsAg loss at the end of the study assessed by measuring HBV genotype only at base line and see if any particular genotype have more HBV sAg loss at the end of the study	At base line & 48 weeks
Secondary	The relationship between IL28B (Interleukin 28B) genotypes ( polymorphism) and HBsAg loss with or without seroconversion to HBs antibody	The relationship between IL28B genotypes ( polymorphism) and HBsAg loss with or without seroconversion to HBs antibody assess by doing IL28B genotypes ( polymorphism) once during the study and see if any specific IL28B genotypes ( polymorphism) associated more with HBV sAg loss at the end of the study with or without seroconversion to HBs antibody).	At base line & 48 weeks
Secondary	The relationship between vitamin D deficiency and (HbsAg loss with or without seroconversion to HBs antibody) assess by measuring Vitamin D level at base line And correlate the baseline level of Vitamin with HBV sAg loss at the end of the study	The relationship between vitamin D deficiency and (HbsAg loss with or without seroconversion to HBs antibody) assess by measuring vitamin D level at base line And correlate the base line level of vitamin D with HBV sAg loss at the end of the study	At base line & 48 weeks

External Links

•   13 European Association for the study of the Liver