A platform study to evaluate investigational therapies in chronic hepatitis B infection
| ISRCTN | ISRCTN29337285 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN29337285 |
| EudraCT/CTIS number | 2022-002014-16 |
| Secondary identifying numbers | VIR-MHB1-200 |
- Submission date
- 25/09/2022
- Registration date
- 28/09/2022
- Last edited
- 27/03/2024
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
The purpose of this research study is to test different experimental study drug(s) in people with chronic hepatitis B virus (HBV) infection. The main goals of the research study are to study if the experimental drugs are safe, how the study drugs interact with the patient’s body, do the study drugs cause any side effects, can the study drugs reduce levels of HBV particles in the body, and measure how much study drugs are found in the blood over time.
Who can participate?
Adults with chronic HBV infection
What does the study involve?
The research study duration for each sub-protocol will have a screening period that could be up to 8 weeks, an on-treatment period that will have a minimum of 8 weeks, and a follow-up period that will have a minimum of 24 weeks. The sub-protocols will include different groups (or cohorts) and each group may evaluate different doses, different dosing schedules, and different combinations of the study drugs. Assignment to a cohort within a sub-protocol will be done in order based on available open cohorts. Study procedures include but are not limited to routine blood and urine tests, HBV blood tests, and physical examinations.
What are the possible benefits and risks of participating?
A possible benefit is that the study drugs may reduce viral particles in the participant’s blood or help activate the immune system to fight HBV. Potential risks in participating are outlined in the participant’s informed consent forms.
Where is the study run from?
Vir Biotechnology Inc (USA)
When is the study starting and how long is it expected to run for?
January 2022 to March 2027
Who is funding the study?
Vir Biotechnology Inc (USA)
Who is the main contact?
Briana (Project Manager) (New Zealand)
Briana.Kawaihae@novotech-cro.com
Contact information
Principal Investigator
Auckland City Hospital
2 Park Road Grafton
Auckland 1010
Auckland
1010
New Zealand
| Phone | +64 21 581 015 |
|---|---|
| liverresearchunit@adhb.govt.nz |
Scientific
499 Illinois St
Suite 500
San Francisco
CA 94158
United States of America
| Phone | +1 415-654-5281 |
|---|---|
| clinicaltrials@vir.bio |
Public
499 Illinois St
Suite 500
San Francisco
CA 94158
United States of America
| Phone | +1 415 654 5281 |
|---|---|
| clinicaltrials@vir.bio |
Study information
| Study design | Multicentre parallel-assignment open-label Phase Ib/II platform study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A platform study evaluating the efficacy and safety of investigational therapies in participants with chronic hepatitis B infection (PREVAIL) |
| Study acronym | PREVAIL |
| Study hypothesis | Phase Ib sub-protocols will be exploratory, and no formal hypothesis testing will be conducted. In phase II sub-protocols, the null hypothesis is that the response rate is the same as in NRTI-suppressed patients. It is assumed that ≤ 2% of NRTI-suppressed patients will achieve a response rate. The alternative hypothesis will be described in the sub-protocol. |
| Ethics approval(s) | Approved 02/09/2022, (Central) Health & Disability Ethics Committee (Ministry of Health, 133 Molesworth Street, PO Box 5013, Wellington, 6011, New Zealand; +64 (0)800 4 38442; hdecs@health.govt.nz), ref: 2022 FULL 12906. |
| Condition | Chronic hepatitis B infection |
| Intervention | Sub-Protocol A (STRIVE): Participants will receive combination therapy with VIR-3434, VIR-2218, PEG-IFNα, and/or TD/TDF up to 48 weeks total Assigned interventions: Drug: VIR-3434 VIR-3434 given by subcutaneous injection Drug: VIR-2218 VIR-2218 given by subcutaneous injection Drug: TD/TDF TD/TDF given orally Drug: PEG-IFNα PEG-IFNα given by subcutaneous injection Sub-Protocol B (THRIVE): Participants will receive combination therapy with VIR-3434, VIR-2218, and/or TD/TDF up to 44 weeks total Assigned interventions: Drug: VIR-3434 VIR-3434 given by subcutaneous injection Drug: VIR-2218 VIR-2218 given by subcutaneous injection Drug: TD/TDF TD/TDF given orally |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | VIR-2218, VIR-3434, pegylated interferon alfa-2a (PEG-IFNα or Pegasys®), tenofovir disoproxil/tenofovir disoproxil fumarate (TD/TDF; Viread®) |
| Primary outcome measure | 1. Proportion of participants achieving sustained suppression of HBV DNA (< lower limit of quantification [LLOQ]) at 24 weeks after discontinuation of all treatment 2. Proportion of participants achieving sustained suppression of HBV DNA (< LLOQ) with HBsAg loss (< 0.05 IU/mL) at 24 weeks after discontinuation of all treatment 3. Proportion of participants with Hepatitis B surface antigen (HBsAg) loss (<0.05 IU/ml) at the end of treatment 4. Proportion of participants with HBsAg loss (<0.05 IU/ml) at 24 weeks post-end of treatment 5. Mean change in serum HBsAg from baseline across time points in the study STRIVE: 6. Proportion of participants with HBsAg loss (< 0.05 IU/ml) at the end of treatment THRIVE: 7. Proportion of participants with HBsAg loss (<0.05 IU/ml) at the end of treatment All outcomes measured using drawn blood |
| Secondary outcome measures | 1. Proportion of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) during the study 2. Proportion of participants with serum HBsAg ≤ 10 IU/ml at end of treatment 3. Proportion of participants with serum HBsAg ≤ 10 IU/ml at 24 weeks post-end of treatment 4. Serum HBsAg levels and change from baseline across time points in the study 5. Serum HBsAg level at nadir during the study 6. Time to achieve nadir of serum HBsAg during the study 7. Time to achieve serum HBsAg loss (< 0.05 IU/ml) 8. Proportion of participants with HBsAg loss with anti-HBs seroconversion at end of treatment and at 24 weeks post-end of treatment STRIVE: 9. Proportion of participants with HBsAg loss (< 0.05 IU/mL) at 24 weeks post-end of treatment 10. Proportion of participants achieving sustained suppression of HBV DNA (< LLOQ) after discontinuation of all treatment: 10.1. At 24 weeks 10.2. At the F48 Follow-Up visit 11. Proportion of participants achieving sustained suppression of HBV DNA (< LLOQ) with HBsAg loss (< 0.05 IU/ml) after discontinuation of all treatment: 11.1. At 24 weeks 11.2. At the F48 Follow-Up visit 12. For HBeAg-positive participants: proportion of participants with HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion 13. Incidence and titers of anti-drug antibodies (ADA; if applicable) to VIR-3434 14. Mean change in serum HBsAg level from baseline across time points in the study 15. Proportion of participants achieving HBV DNA (< LLOQ) across time points in the study 16. Proportion of participants achieving ALT ≤ ULN across time points in the study THRIVE: 9. Proportion of participants with HBsAg loss (< 0.05 IU/mL) at 24 weeks post-end of treatment 10. Proportion of participants achieving sustained suppression of HBV DNA (< LLOQ) after discontinuation of all treatment: 10.1. At 24 weeks 10.2. At 48 weeks 11. Proportion of participants achieving sustained suppression of HBV DNA (< LLOQ) with HBsAg loss (< 0.05 IU/mL) after discontinuation of all treatment 11.1. At 24 weeks 11.2. At 48 weeks 12. Incidence and titers of anti-drug antibodies (ADA; if applicable) to VIR-3434 13. Mean change in serum HBsAg level from baseline across time points in the study 14. Proportion of participants achieving HBV DNA (< LLOQ) All outcomes measured using drawn blood |
| Overall study start date | 30/01/2022 |
| Overall study end date | 05/04/2023 |
| Reason abandoned (if study stopped) | Participant recruitment issue |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Up to 90 (STRIVE) and up to 60 (THRIVE) |
| Participant inclusion criteria | 1. Male or female aged 18 years old and over 2. Chronic HBV infection for >/= 6 months 3. A Body Mass Index (BMI) less than 18 kg/m2 or greater than 35 kg/m2 |
| Participant exclusion criteria | 1. History or current suspicion of malignancy diagnosed or treated within 5 years 2. Any clinically significant medical or psychiatric condition that may interfere with study intervention, assessment, or compliance with the protocol or otherwise makes the participant unsuitable for participation in the study 3. History or evidence of drug or alcohol abuse 4. History of hepatic decompensation |
| Recruitment start date | 18/10/2022 |
| Recruitment end date | 30/04/2025 |
Locations
Countries of recruitment
- New Zealand
Study participating centres
Auckland
1010
New Zealand
Auckland
2025
New Zealand
Tauranga
3110
New Zealand
Hamilton
3204
New Zealand
Sponsor information
Industry
499 Illinois Street
Suite 500
San Francisco, CA
San Francisco
94158
United States of America
| Phone | +1 415-654-5281 |
|---|---|
| clinicaltrials@vir.bio | |
| Website | https://www.vir.bio/ |
"ROR" |
https://ror.org/030pjfg04 |
Industry
Level 6
2-6 Crowhurst Street
Newmarket
Auckland
1023
New Zealand
| Phone | +64 9307 4360 |
|---|---|
| Briana.Kawaihae@novotech-cro.com | |
| Website | https://www.novotech-cro.com/locations/new-zealand |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Vir Biotechnology Inc, Vir Biotechnology, Inc., Vir
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/03/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | A clinical study report for each sub-protocol will be written and may be provided to the appropriate regulatory authorities. This clinical study may be registered, and its results posted on public registries in compliance with local and/or regional regulations. Site-specific results of this study may be published or presented at scientific meetings subject to the terms and requirements of the clinical trial agreement. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Editorial Notes
27/03/2024: The study was withdrawn before recruitment started in NZ due to delays in start-up and lower enrollment potential.
28/09/2023: The overall study end date was changed from 30/03/2027 to 05/04/2023.
28/09/2022: Trial's existence confirmed by the (Central) Health & Disability Ethics Committee, Ministry of Health, New Zealand.
