MARCH: Study of VIR-2218, VIR-3434, and/or PEG-IFNα in Subjects With Chronic Hepatitis B Virus Infection

• Sponsor: Vir Biotechnology, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04856085
• Collaborator: (none)
• Enrollment: 260
• Locations: 32
• Arms: 11
• Anticipated Duration (Months): 70.7
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a phase 2 study in which subjects with chronic hepatitis B virus (HBV) infection will receive VIR-2218, VIR-3434 and/or PEG-IFNα and be assessed for safety, tolerability, and efficacy

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: VIR-2218; Drug: VIR-3434; Drug: PEG-IFNα	Phase 2

Detailed Description

Subjects may be enrolled into cohorts 1a, 2a, 3a, 4a, 5a, 6a, 1b, 2b in a non-randomized manner. Subjects may also be randomized randomized 3:2:2 into cohorts 7a, 8a, or 1c respectively.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 260 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study to Evaluate the Safety, Tolerability, and Efficacy of Regimens Containing VIR-2218, VIR-3434, and/or PEG-IFNα in Subjects With Chronic Hepatitis B Virus Infection
• Actual Study Start Date: Jul 11, 2021
• Anticipated Primary Completion Date: Jun 1, 2027
• Anticipated Study Completion Date: Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1a (VIR-2218 + VIR-3434) Subjects will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 2a (VIR-2218 + VIR-3434) Subjects will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 3a (VIR-2218 + VIR-3434) Subjects will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 4a (VIR-2218 + VIR-3434) Subjects will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 5a (VIR-2218 + VIR-3434) Subjects will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 6a (VIR-2218 + VIR-3434) Subjects will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 7a (VIR-2218 + VIR-3434) Subjects will be randomized 3:2:2 to Cohort 7a, 8a, or 1c respectively. Subjects will receive multiple doses of VIR-2218 + VIR-3434 for 44 weeks	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 8a (VIR-2218 + VIR-3434) Subjects will be randomized 3:2:2 to Cohort 7a, 8a, or 1c respectively. Subjects will receive multiple doses of VIR-2218 + VIR-3434 for 20 weeks	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 1b (VIR-3434) Subjects will receive multiple doses of VIR-3434 for 44 weeks	Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 2b (VIR-3434) Subjects will receive multiple doses of VIR-3434 for 20 weeks	Drug: VIR-3434; VIR-3434 given by subcutaneous injection
Experimental: Cohort 1c (VIR-2218 + VIR-3434) Subjects will be randomized 3:2:2 to Cohort 7a, 8a, or 1c respectively. Subjects will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 24 weeks	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Drug: VIR-3434; VIR-3434 given by subcutaneous injection; Drug: PEG-IFNα; PEG-IFNα given by subcutaneous injection

Outcome Measures

Primary Outcome Measures

1. Proportion of subjects with treatment-emergent adverse events (TEAEs) [Up to 142 weeks]

2. Proportion of subjects with serious adverse events (SAEs) [Up to 142 weeks]

3. Proportion of subjects with HBsAg loss at end of treatment [Up to 44 weeks]

4. Proportion of subjects with HBsAg loss at 24 weeks post-end of treatment [Up to 68 weeks]

Secondary Outcome Measures

1. Absolute serum HBsAg and change from baseline across all timepoints in the study [Up to 142 weeks]

2. Time to achieve the nadir and maximum reduction of serum HBsAg from baseline [Up to 142 weeks]

3. Proportion of subjects with serum HBsAg loss (defined as undetectable HBsAg) [Up to 142 weeks]

4. For hepatitis B e-antigen (HBeAg)-positive subjects: Proportion of subjects with HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion at any timepoint [Up to 142 weeks]

5. For HBeAg-positive subjects: Time to HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion [Up to 142 weeks]

6. Cmax [Up to 64 weeks]

7. Clast [Up to 64 weeks]

8. Tmax [Up to 64 weeks]

9. Tlast [Up to 64 weeks]

10. AUCinf [Up to 64 weeks]

11. AUClast [Up to 64 weeks]

12. %AUCexp [Up to 64 weeks]

13. t1/2 [Up to 64 weeks]

14. λz [Up to 64 weeks]

15. Vz/F [Up to 64 weeks]

16. CL/F [Up to 64 weeks]

17. Number of subjects with incidence and titers of anti-drug antibody (ADA) (if applicable) to VIR-3434 [Up to 142 weeks]

18. Proportion of subjects meeting criteria for nucleotide reverse transcriptase inhibitors (NRTI) discontinuation [Up to 92 weeks]

19. Proportion of subjects meeting criteria for NRTI retreatment [Up to 142 weeks]

20. Proportion of subjects achieving undetectable hepatitis B surface antigen (HBsAg) and sustained suppression of HBV DNA [target not detected (TND)] >/= 24 weeks after discontinuation of all treatment, including NRTIs [Up to 142 weeks]

21. Proportion of subjects with serum HBsAg < 10 IU/mL at end of treatment [Up to 44 weeks]

22. Proportion of subjects with serum HBsAg < 10 IU/mL at 24 weeks post-end of treatment [Up to 68 weeks]

    44 weeks and 24 weeks post-end of treatment

23. Proportion of subjects with anti-HBs seroconversion [Up to 142 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female ages 18 - <66 years

• Chronic HBV infection for >/= 6 months

• On NRTI therapy for >/= 2 months at the time of screening

Exclusion Criteria:

• Any clinically significant chronic or acute medical condition that makes the participant unsuitable for participation

• Significant fibrosis or cirrhosis

• History or evidence of drug or alcohol abuse

• History of chronic liver disease from any cause other than chronic HBV infection

• History of hepatic decompensation

• History of anaphylaxis

• History of allergic reactions, hypersensitivity, or intolerance to monoclonal antibodies, antibody fragments, or any excipients of VIR-3434

• History of immune complex disease

• History of known contraindication to any interferon product

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigative Site	Frankfurt		Germany	60590
2	Investigative Site	Hannover		Germany	30625
3	Investigative Site	Mannheim		Germany	68167
4	Investigative Site	Ulm		Germany	89081
5	Investigative Site	Hong Kong	Shatin	Hong Kong
6	Investigative Site	Hong Kong	Tai Po	Hong Kong
7	Investigative Site	Hong Kong		Hong Kong
8	Investigative Site	Busan		Korea, Republic of	49421
9	Investigative Site	Seoul		Korea, Republic of	03080
10	Investigative Site	Seoul		Korea, Republic of	05505
11	Investigative Site	Yangsan		Korea, Republic of	50612
12	Investigative Site	Batu Caves		Malaysia	68100
13	Investigative Site	Kajang		Malaysia	43000
14	Investigative Site	Kuala Lumpur		Malaysia	59100
15	Investigative Site	Chisinau		Moldova, Republic of
16	Investigative Site	Auckland		New Zealand	1010
17	Investigative Site	Auckland		New Zealand	2025
18	Investigative Site	Hamilton		New Zealand	3204
19	Investigative Site	Tauranga		New Zealand	3110
20	Investigative Site	Wellington		New Zealand	6021
21	Investigative Site	Bucharest		Romania
22	Investigative Site	Chiayi City		Taiwan	60041
23	Investigative Site	Kaohsiung City		Taiwan	80756
24	Investigative Site	Kaohsiung City		Taiwan	83301
25	Investigative Site	Taichung City		Taiwan	40705
26	Investigative Site	Taipei City		Taiwan	100
27	Investigative Site	Taoyuan City		Taiwan	33305
28	Investigative Site	Kyiv		Ukraine	08132
29	Investigative Site	Birmingham		United Kingdom	B15 2TH
30	Investigative Site	London		United Kingdom	E1 4NS
31	Investigative Site	London		United Kingdom	SE5 9RS
32	Investigative Site	Manchester		United Kingdom	M8 5RB

Sponsors and Collaborators

• Vir Biotechnology, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Vir Biotechnology, Inc.
• ClinicalTrials.gov Identifier: NCT04856085
• Other Study ID Numbers: VIR-2218-1006
• First Posted: Apr 22, 2021
• Last Update Posted: Jul 20, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Vir Biotechnology, Inc.: Hepatitis B Virus; Chronic Hepatitis B; HBV; Hepatitis
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Virus Diseases; Herpesviridae Infections; Hepatitis; Hepatitis, Chronic

Study Results

No Results Posted as of Jul 20, 2022