Combined Therapy With Peginterferon Alfa-2a With NA in NA-treated HBeAg Positive Patients

Chronic Hepatitis B Clinical Trial

Official title:

A Prospective, Randomized, Multicenter, Open-label Study Evaluating HBeAg Seroconversion in HBeAg Positive CHB Patients on Treatment With NA Switched to Combined Therapy With Peginterferon Alfa-2a and NA for 48 Weeks

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02474316
• Other study ID #: HOPE
• Status: Recruiting
• Phase: Phase 4
• First received: March 25, 2015
• Last updated: December 2, 2015
• Start date: August 2014
• Est. completion date: December 2017

Study information

• Verified date: June 2015
• Source: Ruijin Hospital
• Contact: Qing Xie
• Phone: 86-13651804273
• Email: xieqingrjh2015[@]gmail.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This is a prospective, randomized, multicenter, open-label study. After more than 24 weeks NA treatment, HBeAg positive CHB patients who achieved HBV DNA<1000copies/ml but HBeAb negative, will be randomized (1:1) into 2 study arms as follows:

Arm A: Peginterferon alfa-2a 180μg /wk plus NA 1 piece qd for 48 weeks Arm B: Entecavir 0.5mg qd for 48 weeks

Description:

This is a prospective, randomized, multicenter, open-label study. After more than 24 weeks NA treatment, HBeAg positive CHB patients who achieved HBV DNA<1000copies/ml but HBeAb negative, will be randomized (1:1) into 2 study arms as follows:

Arm A: Peginterferon alfa-2a 180μg /wk plus NA 1piece qd for 48 weeks Arm B:NA 1 piece qd for 48 weeks

The primary endpoint: HBeAg seroconversion at week 48

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 366
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion criteria:

1. Male and female patients with age =18 and =65 years;

2. There should be evidences that HBsAg and HBeAg have been positive for more than 6 months with HBsAb and HBeAb negative before treated with Entecavir;

3. Treated with NA for more than 24 weeks and achieve HBV DNA<1000copies/ml with HBeAb negative;

4. Women without ongoing pregnancy or breast feeding and willing to take an effective contraceptive measure during the treatment

5. Agree to participate in the study and sign the patient informed consent.

Exclusion Criteria:

1. Co-infection with active hepatitisA, hepatitisC, hepatitisD and/or human immunodeficiency virus (HIV)

2. AFP>50ng/ml and/or evidence of hepatocellular carcinoma

3. Evidence of decompensated liver disease (Child-Pugh scores >5). Child-Pugh >5 means that, if one of the following 6 conditions is met, the patient has to be excluded:

1. Serum albumin <35 g/L;

2. Prothrombine time prolonged= 4 seconds or PTA < 60%;

3. Serum bilirubin > 34 µmol/L;

4. History of encephalopathy;

5. Ascites

4. History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures, thalassemia)

5. Pregnant or breast-feeding Women

6. ANC<1.5x 10^9/L or PLT<90x 10^9/L

7. Consuming alcohol in excess of 20g/day for women and 30g/day for men within 6 months prior to enrollment

8. History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as major depression or psychosis that treated with antidepressant medication or a major tranquilizer at therapeutic doses respectively at any time prior to 3 months or any history of the following: a suicidal attempt hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease

9. History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.)

10. History of esophageal varices bleeding or other evidence of esophageal varices bleeding or other symptoms consistent with decompensated liver disease

11. History of chronic pulmonary disease associated with functional limitation

12. History of severe cardiac disease (e.g., NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases)

13. Hemodialysis patients or patients with renal insufficiency

14. History of a severe seizure disorder or current anticonvulsant use

15. Major organ transplantation or other evidence of severe illness, malignancy, or any other conditions, which would make the patient, in the opinion of the investigator, unsuitable for the study

16. History of thyroid disease poorly controlled on prescribed medications

17. Evidence of severe retinopathy or clinically relevant ophthalmologic disorder

18. History of other severe disease or evidence of other severe disease or any other illness or conditions that the investigator believe that patients are not suitable to join in the study

19. Immunomodulatory treatment (including interferon) or LDT within 1 year prior to the first dose of treatment

20. Patients included in another trial or having been given investigational drugs within 12 weeks prior to screening

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Peginterferon alfa-2a
Peginterferon alfa-2a 180ug/wk s.c for 48 weeks
• nucleos(t)ide analgoue
nucleos(t)ide analgoue (NA) 1 piece p.o for 48 weeks

Locations

Country	Name	City	State
China	The Third People's Hospital of Guilin	Guilin
China	Ruijin Hospital	Shanghai
China	Shanghai Public Health Clinical Center	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

Brouwer WP, Xie Q, Sonneveld MJ, Zhang N, Zhang Q, Tabak F, Streinu-Cercel A, Wang JY, Idilman R, Reesink HW, Diculescu M, Simon K, Voiculescu M, Akdogan M, Mazur W, Reijnders JG, Verhey E, Hansen BE, Janssen HL; ARES Study Group. Adding pegylated interfe — View Citation

Chang TT, Lai CL, Kew Yoon S, Lee SS, Coelho HS, Carrilho FJ, Poordad F, Halota W, Horsmans Y, Tsai N, Zhang H, Tenney DJ, Tamez R, Iloeje U. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepato — View Citation

Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet. 2003 Dec 20;362(9401):2089-94. Review. — View Citation

Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, Jeffers L, Goodman Z, Wulfsohn MS, Xiong S, Fry J, Brosgart CL; Adefovir Dipivoxil 437 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. — View Citation

Tassopoulos NC, Volpes R, Pastore G, Heathcote J, Buti M, Goldin RD, Hawley S, Barber J, Condreay L, Gray DF. Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamiv — View Citation

Trépo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014 Dec 6;384(9959):2053-63. doi: 10.1016/S0140-6736(14)60220-8. Epub 2014 Jun 18. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants who achieve HBeAg seroconversion	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the HBeAg seroconversion in HBeAg positive CHB patients on treatment with Entecavir and with HBV DNA <1000copies/ml which will be measured by the number of participants who achieve HBeAg seroconversion	at week 48	Yes
Secondary	Number of participants who achieve HBeAg loss	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBeAg seroconversion which will be measured by number of participants who achieve HBeAg loss	at week 48	No
Secondary	Number of participants who achieve HBsAg loss	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBsAg loss which will be measured by number of participants who achieve HBsAg loss	at week 48	No
Secondary	Number of participants who achieve HBsAg seroconversion	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBsAg seroconversion which will be measured by number of participants who achieve HBsAg seroconversion	at week 48	No
Secondary	HBsAg decline from baseline	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBsAg decline from baseline	at week 48	No
Secondary	Percentage of participants who achieve HBsAg <1000IU/mL	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the percentage of participants who achieve HBsAg<1000IU/mL	at week 48	No
Secondary	Percentage of of participants who achieve HBsAg <100IU/mL	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the percentage of of participants who achieve HBsAg<100IU/mL	at week 48	No
Secondary	Number of participants who achieve combined response I (defined as HBeAg seroconversion and HBV DNA<100000copies/mL)	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the combined response I which will be measured by number of participants who achieve combined response I	at week 48	No
Secondary	Number of participants who achieve combined response II (defined as HBeAg seroconversion and HBV DNA<1000copies/mL)	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the combined response II which will be measured by number of participants who achieve combined response II	at week 48	No
Secondary	Number of participants who achieve dural response I (defined as HBeAg seroconversion and HBsAg<1000IU/mL)	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the dural response I which will be measured by number of participants who achieve dural response I	at week 48	No
Secondary	Number of participants who achieve dural response II (defined as HBeAg seroconversion and HBsAg<100IU/mL)	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the dural response II which will be measured by number of participants who achieve dural response II	at week 48	No
Secondary	Number of Participants with AE	Number of participants with adverse events as a measure of safety and tolerability	at week 48	Yes
Secondary	Number of Participants with SAE	Number of participants with SAEs as a measure of safety and tolerability	at week 48	Yes