B-Together: Study of Sequential GSK3228836 and Peginterferon Treatment in Participants With Chronic Hepatitis B (CHB)

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04676724
Collaborator
(none)
100
49
2
24.6
2
0.1

Study Details

Study Description

Brief Summary

This study is intended to evaluate if 12 or 24 weeks of treatment with GSK3228836 followed by up to 24 weeks of pegylated interferon (PegIFN) can increase the rate of hepatitis B virus surface antigen (HBsAg) loss in participants on stable nucleos(t)ide analogue (NA) therapy, and whether virologic response can be sustained once PegIFN treatment is discontinued. Participants will be randomized to receive GSK3228836 for 12 or 24 weeks followed by up to 24 weeks of PegIFN.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Participants will be randomised in a ratio of 1:1 to one of two treatment arms: 24 weeks GSK3228836 followed by up to 24 weeks PegIFN, or 12 weeks GSK3228836 followed by up to 24 weeks PegIFN.Participants will be randomised in a ratio of 1:1 to one of two treatment arms: 24 weeks GSK3228836 followed by up to 24 weeks PegIFN, or 12 weeks GSK3228836 followed by up to 24 weeks PegIFN.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase IIb Multi-Center, Randomised, Open Label Study to Assess the Efficacy and Safety of Sequential Treatment With GSK3228836 Followed by Pegylated Interferon Alpha 2a in Participants With Chronic Hepatitis B Virus (B-Together)
Actual Study Start Date :
Jan 28, 2021
Anticipated Primary Completion Date :
Feb 17, 2023
Anticipated Study Completion Date :
Feb 17, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: GSK3228836 for 24 weeks + PegIFN for up to 24 weeks

Eligible participants on stable NA therapy will receive GSK3228836 for 24 weeks, followed by up to 24 weeks of PegIFN.

Drug: GSK3228836
Participants will be administered GSK3228836.

Drug: PegIFN
Participants will be administered PegIFN.

Drug: NA therapy
Participants will continue to receive their NA therapy for the duration of the study.

Experimental: GSK3228836 for 12 weeks + PegIFN for up to 24 weeks

Eligible participants on stable NA therapy will receive GSK3228836 for 12 weeks, followed by up to 24 weeks of PegIFN.

Drug: GSK3228836
Participants will be administered GSK3228836.

Drug: PegIFN
Participants will be administered PegIFN.

Drug: NA therapy
Participants will continue to receive their NA therapy for the duration of the study.

Outcome Measures

Primary Outcome Measures

  1. Percentage of participants who achieve sustained virologic response (SVR) for 24 weeks after end of treatment [From off-treatment Week 1 to off-treatment Week 24]

    Sustained virologic response is defined as undetectable levels of HBsAg and Hepatitis-B virus deoxy-ribonucleic acid (HBV DNA) on treatment.

Secondary Outcome Measures

  1. Percentage of participants achieving HBsAg and HBV DNA < lower limit of quantitation (LLOQ) [From off-treatment Week 1 to off-treatment Week 24]

    Percentage of participants achieving HBsAg and HBV DNA <LLOQ.

  2. Percentage of participants with alanine aminotransferase (ALT) normalization over time in absence of rescue medication [Up to 72 weeks]

    Limited to participants having Baseline ALT> upper limit of normal (ULN).

  3. Absolute values of HBsAg levels [Up to 72 weeks]

    Blood samples will be collected to assess HBsAg levels.

  4. Change from Baseline in HBsAg levels [Baseline and up to 72 weeks]

    Blood samples will be collected to assess HBsAg levels.

  5. Absolute values of HBV DNA levels [Up to 72 weeks]

    Blood samples will be collected to assess HBV DNA levels.

  6. Change from Baseline in HBV DNA levels [Baseline and up to 72 weeks]

    Blood samples will be collected to assess HBV DNA levels.

  7. Absolute values of Hepatitis B virus e-antigen (HBeAg) levels [Up to 72 weeks]

    Blood samples will be collected to assess HBeAg levels.

  8. Change from Baseline in HBeAg levels [Baseline and up to 72 weeks]

    Blood samples will be collected to assess HBeAg levels.

  9. Absolute values of HBs antibody levels [Up to 72 weeks]

    Blood samples will be collected to assess HBs antibody levels.

  10. Change from Baseline in HBs antibody levels [Baseline and up to 72 weeks]

    Blood samples will be collected to assess HBs antibody levels.

  11. Absolute values of HBe antibody levels [Up to 72 weeks]

    Blood samples will be collected to assess HBe antibody levels.

  12. Change from Baseline in HBe antibody levels [Baseline and up to 72 weeks]

    Blood samples will be collected to assess HBe antibody levels.

  13. Absolute values of ALT [Up to 72 weeks]

    Blood samples will be collected to assess ALT levels.

  14. Change from Baseline in ALT [Baseline and up to 72 weeks]

    Blood samples will be collected to assess ALT levels.

  15. Time to ALT normalization in absence of rescue medication [Baseline and up to 72 weeks]

    Time to ALT normalization in absence of rescue medication will be measured in participants having Baseline ALT>ULN.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • 18 to 75 years of age at the time of signing the informed consent.

  • Participants who are eligible to be treated with PegIFN.

  • Documented chronic HBV infection >=6 months prior to screening and currently receiving stable NA therapy except telbivudine, defined as no changes to their NA regimen from at least 6 months prior to screening and with no planned changes to the stable regimen over the duration of the study.

  • Plasma or serum HBsAg concentration >100 International Units per milliliter (IU/mL).

  • Plasma or serum HBV DNA concentration <90 IU/mL.

  • ALT <=2 times ULN.

  • A male participant is eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of study treatment: a) Refrain from donating sperm; b) Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or agree to use contraception/barrier: Agree to use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak) when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.

  • A female participant is eligible to participate: a) If she is not pregnant or breastfeeding; b) at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) or is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1 percent per year), preferably with low user dependency during the intervention period and for at least 90 days after the last dose of study treatment.

  • A WOCBP must have both a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

  • Capable of giving signed informed consent.

Exclusion Criteria:
  • Clinically significant abnormalities, aside from chronic HBV infection in medical history or physical examination.

  • Co-infection with: Current or past history of Hepatitis C virus (HCV); Human immunodeficiency virus (HIV); Hepatitis D virus (HDV).

  • History of or suspected liver cirrhosis and/or evidence of cirrhosis as determined by both: Aspartate aminotransferase (AST)-Platelet Index (APRI) >2 and FibroSure/FibroTest result >0.7. If only one parameter (APRI or FibroSure/FibroTest) result is positive, a discussion with the Medical Monitor is required before inclusion in study is permitted. Regardless of APRI of Fibrosure/FibroTest score, if the participant meets one of the following criteria, they will be excluded from the study:

  1. Liver biopsy (i.e., Metavir Score F4); b) Liver stiffness >12 kilopascals (kPa).
  • Diagnosed or suspected hepatocellular carcinoma as evidenced by the following: Alpha- fetoprotein concentration >=200 nanogram per milliliter (ng/mL); If the screening alpha fetoprotein concentration is >=50 ng/mL and <200 ng/mL, the absence of liver mass must be documented by imaging within 6 months before randomization.

  • History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer). Participants under evaluation for possible malignancy are not eligible.

  • History of vasculitis or presence of symptoms and signs of potential vasculitis (e.g., vasculitic rash, skin ulceration, repeated blood detected in urine without identified cause) or history/presence of other diseases that may be associated with vasculitis condition (e.g., systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex).

  • History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, uncontrolled hypertension).

  • Poorly controlled thyroid dysfunction or abnormal thyroid stimulating hormone (TSH) levels

  • Positive (or borderline positive) anti-neutrophil cytoplasmic antibody (ANCA) at screening. Participants that meet these criteria may be considered for inclusion in the study following: a) Analysis of myeloperoxidase (MPO)-ANCA [perinuclear ANCA (pANCA)] and PR3-ANCA [classical ANCA (cANCA)]; b) A discussion with the Medical Monitor to review participant's complete medical history to ensure no past history or current manifestations of a vasculitic/inflammatory/auto-immune condition.

  • Low complement 3 (C3) at screening and evidence of past history or current manifestations of vasculitic/inflammatory/auto-immune conditions. All participants with low C3 at screening should have their medical history discussed with the Medical Monitor prior to enrolment.

  • History of alcohol or drug abuse/dependence. Current alcohol use as judged by investigator to potentially interfere with participant compliance; History of or current drug abuse/dependence as judged by the investigator to potentially interfere with participant compliance. Refers to illicit drugs and substances with abuse potential. Medications that are used by the participant as directed, whether over-the-counter or through prescription, are acceptable and would not meet the exclusion criteria.

  • Pre-existing severe psychiatric condition or a history of severe psychiatric disorders, including severe depression, suicidal ideation and attempted suicide.

  • Currently taking, or took within 3 months of screening, any immunosuppressing drugs (e.g., prednisone), other than a short course of therapy (<=2 weeks) or topical/inhaled steroid use.

  • Participants for whom immunosuppressive treatment is not advised, including therapeutic doses of steroids, will be excluded.

  • Participants with prior treatment with PegINF or interferon will be excluded

  • Participants requiring anti-coagulation therapies (for example warfarin, Factor Xa inhibitors or anti-platelet agents like clopidogrel).

  • Participants currently taking, or took within 6 months of screening, telbivudine.

  • The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives (if known) or twice the duration (if known) of the biological effect of the study treatment (whichever is longer) or 90 days (if half-life or duration is unknown).

  • Prior treatment with any oligonucleotide or small interfering ribonucleic acid (siRNA) within 12 months prior to the first dosing day.

  • Fridericia's QT correction formula (QTcF) >=450 milliseconds (msec) (if single electrocardiogram [ECG] at screening shows QTcF>=450 msec, a mean of triplicate measurements should be used to confirm that participant meets exclusion criterion).

  • Laboratory results as follows: Serum albumin <3.5 grams per deciliter (g/dL); Glomerular filtration rate (GFR) <60 milliliter per minute per 1.73 square meter (mL/min /1.73 m^2) as calculated by the Chronic Kidney Disease Epidemiologic Collaboration (CKD-EPI) formula (for Japan, Japanese Society of Nephrology Chronic Kidney Disease Initiative [JSN-CKDI equation]); International normalized ratio (INR)

1.25; Platelet count <140x10^9 cells/L; Baseline hemoglobin <10 g/dL; Total bilirubin 1.25 times ULN (For participants with benign unconjugated hyperbilirubinemia with total bilirubin >1.25 times ULN, discussion for inclusion to the study is required with the Medical Monitor); Urine albumin to creatinine ratio (ACR) >=0.03 milligram (mg)/mg (or >=30 mg/g). In the event of an ACR above this threshold, eligibility may be confirmed by a second measurement. In cases where participants have low urine albumin and low urine creatinine levels resulting in a urine ACR calculation >=0.03 mg/mg (or >=30 mg/g), the investigator should confirm that the participant does not have a history of diabetes, hypertension or other risk factors that may affect renal function and discuss with the Medical Monitor, or designee.

  • History of/sensitivity to GSK3228836 or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Sacramento California United States 95817
2 GSK Investigational Site Iowa City Iowa United States 52242
3 GSK Investigational Site Detroit Michigan United States 48202
4 GSK Investigational Site New York New York United States 10016
5 GSK Investigational Site Calgary Alberta Canada T2N 4Z6
6 GSK Investigational Site Edmonton Alberta Canada T6G 2X8
7 GSK Investigational Site Montreal Quebec Canada H2L 4E9
8 GSK Investigational Site Changchun Jilin China 130021
9 GSK Investigational Site Beijing China 100015
10 GSK Investigational Site Beijing China 100069
11 GSK Investigational Site Hangzhou China 310000
12 GSK Investigational Site Shanghai China 200025
13 GSK Investigational Site Baggiovara (MO) Emilia-Romagna Italy 40126
14 GSK Investigational Site Milano Lombardia Italy 20122
15 GSK Investigational Site Milano Lombardia Italy 20157
16 GSK Investigational Site Monza (MB) Lombardia Italy 20900
17 GSK Investigational Site Aichi Japan 467-8602
18 GSK Investigational Site Fukui Japan 918-8503
19 GSK Investigational Site Gifu Japan 500-8717
20 GSK Investigational Site Hiroshima Japan 737-0023
21 GSK Investigational Site Kumamoto Japan 860-8556
22 GSK Investigational Site Nagasaki Japan 856-8562
23 GSK Investigational Site Tokyo Japan 113-8603
24 GSK Investigational Site Busan Korea, Republic of 49241
25 GSK Investigational Site Daegu Korea, Republic of 41944
26 GSK Investigational Site Gyeonggi-do Korea, Republic of 15355
27 GSK Investigational Site Gyeonggi-do Korea, Republic of 463-712
28 GSK Investigational Site Ulsan Korea, Republic of 44033
29 GSK Investigational Site Lancut Poland 37-100
30 GSK Investigational Site Lublin Poland 20-884
31 GSK Investigational Site Myslowice Poland 41-400
32 GSK Investigational Site Barnaul Russian Federation 656010
33 GSK Investigational Site Chelyabinsk Russian Federation 454052
34 GSK Investigational Site Krasnojarsk Russian Federation 660049
35 GSK Investigational Site Moscow Russian Federation 121170
36 GSK Investigational Site Novosibirsk Russian Federation 630099
37 GSK Investigational Site Samara Russian Federation 443063
38 GSK Investigational Site St. Petersburg Russian Federation 190103
39 GSK Investigational Site Ennerdale Gauteng South Africa 1830
40 GSK Investigational Site Johannesburg Gauteng South Africa 1401
41 GSK Investigational Site Barcelona Spain 08011
42 GSK Investigational Site Barcelona Spain 08035
43 GSK Investigational Site Madrid Spain 28031
44 GSK Investigational Site Málaga Spain 29010
45 GSK Investigational Site Santander Spain 39008
46 GSK Investigational Site London United Kingdom WC1E 6JB
47 GSK Investigational Site Newcastle-upon-Tyne United Kingdom NE7 7DN
48 GSK Investigational Site Nottingham United Kingdom NG7 2UH
49 GSK Investigational Site Plymouth United Kingdom PL68DH

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT04676724
Other Study ID Numbers:
  • 209348
First Posted:
Dec 21, 2020
Last Update Posted:
Aug 25, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 25, 2022