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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05343481




Registration number
NCT05343481
Ethics application status
Date submitted
12/04/2022
Date registered
25/04/2022

Titles & IDs
Public title
Efficacy of VTP-300 in Chronic Hepatitis B Infection
Scientific title
A Phase 2b, Open-label Study to Evaluate the Efficacy, Safety, Tolerability, Immunogenicity and Treatment Regimens of VTP-300 Combined With Low-dose Nivolumab in Chronic Hepatitis B Infection
Secondary ID [1] 0 0
HBV-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - ChAdOx1-HBV
Treatment: Other - MVA-HBV
Treatment: Other - Nivolumab

Experimental: Experimental: Group 1 ChAdOx1-HBV, MVA-HBV and nivolumab - Day 1: ChAdOx1-HBV 1 x 2.5 10\^10 vp IM injection Day 29: MVA-HBV 1 x 10\^8 pfu IM injection + nivolumab 0.3 mg/kg IV infusion

Experimental: Experimental: Group 2 ChAdOx1-HBV, MVA-HBV and nivolumab, MVA-HBV and nivolumab - Day 1: ChAdOx1-HBV 1 x 2.5 10\^10 vp IM injection Day 29: MVA-HBV 1 x 10\^8 pfu IM injection + nivolumab 0.3 mg/kg IV infusion Day 85: MVA-HBV 1 x 10\^8 pfu IM injection + nivolumab 0.3 mg/kg IV infusion

Experimental: Experimental: Group 3 ChAdOx1-HBV, MVA-HBV, nivolumab, MVA-HBV - Day 1: ChAdOx1-HBV 1 x 2.5 10\^10 vp IM injection Day 29: MVA-HBV 1 x 10\^8 pfu IM injection Day 36: Nivolumab 0.3 mg/kg IV infusion Day 85: MVA-HBV 1 x 10\^8 pfu IM injection


Treatment: Other: ChAdOx1-HBV
Chimpanzee Adenovirus Oxford 1-vectored Hepatitis B virus immunotherapeutic

Treatment: Other: MVA-HBV
Modified Vaccinia Ankara-vectored Hepatitis B virus immunotherapeutic

Treatment: Other: Nivolumab
Human immunoglobulin G4 monoclonal antibody
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The incidence of participants with a greater than 1 log HBsAg
Timepoint [1] 0 0
6 months after the initiation of therapy
Secondary outcome [1] 0 0
The incidence of participants with Treatment-Emergent Adverse Events (TEAEs) and =Grade 3 related adverse events following study treatment
Timepoint [1] 0 0
From each study vaccination for the following 7 days
Secondary outcome [2] 0 0
The incidence of participants with Treatment-Emergent Adverse Events (TEAEs) and =Grade 3 related adverse events following administration with nivolumab
Timepoint [2] 0 0
From each study administration with nivolumab for the following 7days
Secondary outcome [3] 0 0
The incidence of participants with Adverse Events of Special Interest (AESIs)
Timepoint [3] 0 0
From study admission (the signature of informed consent) to the end of the study (Month 12)
Secondary outcome [4] 0 0
The incidence of participants with Treatment-Emergent Adverse Events (TEAEs) within each study group
Timepoint [4] 0 0
From each study administration for the following 7 days
Secondary outcome [5] 0 0
Incidence of participants with potentially clinically significant laboratory signs within each treatment group as assessed by the Investigator
Timepoint [5] 0 0
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336
Secondary outcome [6] 0 0
Incidence of participants with potentially clinically significant vital signs within each treatment group as assessed by the Investigator
Timepoint [6] 0 0
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336
Secondary outcome [7] 0 0
Number of participants with worst changes from baseline in laboratory hematology parameters
Timepoint [7] 0 0
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336
Secondary outcome [8] 0 0
Number of participants with worst changes from baseline in laboratory biochemistry parameters
Timepoint [8] 0 0
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336
Secondary outcome [9] 0 0
Number of participants with worst changes from baseline in laboratory urinalysis parameters
Timepoint [9] 0 0
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336
Secondary outcome [10] 0 0
Number of participants with worst changes from baseline in vital signs parameters (heart rate, systolic blood pressure, diastolic blood pressure and temperature)
Timepoint [10] 0 0
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336
Secondary outcome [11] 0 0
T cell response to the HBV antigen inserts of VTP-300 as measured by interferon (IFN)-? enzyme-linked immunospot (ELISpot)
Timepoint [11] 0 0
Baseline, Day 8, Day 29, Day 36, Day 57, Day 85, Day 92, Day 113, Day 169, Day 252 and Day 336

Eligibility
Key inclusion criteria
1. Adult males or females aged =18 to =65 years at screening (according to country/local regulations)
2. BMI =35 kg/m2
3. Able to provide informed consent indicating they understand the purpose of, and procedures required, for the study and are willing to participate
4. If female, willing not to become pregnant up to 8 weeks after the last dose of study vaccine and up to 5 months after the last dose of nivolumab
5. If female: Not pregnant or breast feeding and one of the following:

* Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in =1 year and without an alternative medical cause)
* Of childbearing potential but agrees to practice highly effective contraception for 4 weeks prior to study vaccine and 8 weeks after VTP-300 and 5 months after the last dose of nivolumab. Highly effective methods of contraception include one or more of the following:

* Male partner who is sterile (medically effective vasectomy) prior to the female participant's entry into the study and is the sole sexual partner for the female participant
* Combined (oestrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal or transdermal
* Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable or implantable
* An intrauterine device
* Bilateral tubal occlusion
* Abstinence from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
6. Documented evidence of CHB infection (e.g., HBsAg positive =6 months with detectable HBsAg levels at screening; both HBeAg+ and HBeAg- allowed)
7. Receipt of only either entecavir, tenofovir (tenofovir alafenamide fumarate or tenofovir disoproxil fumarate) or besifovir for at least 6 months before screening
8. HBV-DNA viral load = 1,000 IU/mL
9. HBsAg levels > 10 and = 4,000 IU/mL
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of any significant acute or chronic, uncontrolled medical or psychiatric illness in the opinion of the investigator would affect the safety of the participant or the evaluation of the data or interfere with adherence to the study requirements
2. Medical history that is thought to increase the participant's risk of reaction to a vaccine, including but not limited to capillary leak syndrome; transverse myelitis, Guillain Barré syndrome, thrombosis with thrombocytopenia syndrome (also termed vaccine-induced thrombotic thrombocytopenia); heparin-induced thrombocytopenia HCV RNA positive
3. HIV antibody positive and active hepatitis C (antibody positive and then DNA positive)
4. Co-infection with hepatitis D virus (HDV)
5. Documented cirrhosis or advanced fibrosis indicated by a liver biopsy within 6 months prior to Day 0 (Metavir activity grade A4 and stage F4; Ishak stages 5 - 6).
6. In the absence of a documented liver biopsy, either 1 of the following (not both):

* Screening Fibroscan with a result >9 kilopascals (kPa) (or the equivalent) within = 6 months of screening, OR
* Both screening FibroTest >0.48 and aspartate aminotransferase (AST) to platelet ratio index (APRI) of >1.
7. ALT >3 x ULN, or INR >1.5 unless the participant was stable on an anticoagulant regimen affecting INR, albumin <3.2 g/dL, direct bilirubin >1.5 x ULN, platelet count <100,000/µL.
8. A history of liver decompensation (e.g., ascites, encephalopathy or variceal haemorrhage)
9. Prior hepatocellular carcinoma
10. Chronic liver disease of a non-HBV aetiology. (Note that Gilbert's syndrome, asymptomatic gallstones and non-alcoholic fatty liver not associated with steatohepatitis are not exclusions)
11. History or evidence of autoimmune disease or known immunodeficiency of any cause except history of autoimmune thyroiditis if the participant is stable on replacement therapy
12. Evidence of interstitial lung disease, active pneumonitis, myocarditis or a history of myocarditis
13. Prolonged therapy with immunomodulators (e.g., corticosteroids such as prednisone >10 mg/day) or biologics (e.g., monoclonal antibodies, IFN) within 3 months of Day 1. Inhaled, intra-articular, intra-bursal or topical corticosteroids are allowed. Physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency is allowed.
14. Receipt of immunoglobulin or other blood products within 3 months prior to Day 1
15. Receipt of any investigational drug or vaccine within 3 months prior to Day 1
16. Receipt of any non-oral adenoviral-based vaccine within 3 months prior to administration of ChAdOx1-HBV on Day 1
17. Severe reaction to any vaccine, requiring medical attention
18. Receipt of any live vaccines within 30 days prior to Day 1
19. Receipt of any inactivated non-live vaccines (e.g., mRNA, inactivated vaccines, toxoid vaccines) within 14 days prior to Day 1
20. History of severe hypersensitivity or anaphylactic reactions likely to be exacerbated by any component of VTP-300 or nivolumab, including severe allergy to egg
21. Malignancy within 5 years prior to screening with the exception of basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. Participants under evaluation for possible malignancy are not eligible
22. Current alcohol or substance abuse judged by the investigator to potentially interfere with participant safety or compliance
23. Any laboratory test which is abnormal, and which is deemed by the investigator to be clinically significant
24. Any other finding that, in the opinion of the investigator, deems the participant unsuitable for the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/09/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2026
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Hong Kong
State/province [1] 0 0
Hong Kong
Country [2] 0 0
Taiwan
State/province [2] 0 0
Chiayi City
Country [3] 0 0
Taiwan
State/province [3] 0 0
Kaohsiung
Country [4] 0 0
Taiwan
State/province [4] 0 0
Taichung City
Country [5] 0 0
Taiwan
State/province [5] 0 0
Tainan City
Country [6] 0 0
Taiwan
State/province [6] 0 0
Taipei
Country [7] 0 0
Taiwan
State/province [7] 0 0
Taoyuan City
Country [8] 0 0
Thailand
State/province [8] 0 0
Bangkok
Country [9] 0 0
Thailand
State/province [9] 0 0
Chiang Mai
Country [10] 0 0
Thailand
State/province [10] 0 0
Khon Kaen
Country [11] 0 0
Thailand
State/province [11] 0 0
Mueang Nonthaburi

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Barinthus Biotherapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05343481