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Study of VIR-2218 in Healthy Subjects and Patients With Chronic Hepatitis B

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03672188
Recruitment Status : Completed
First Posted : September 14, 2018
Results First Posted : December 13, 2021
Last Update Posted : December 13, 2021
Sponsor:
Collaborator:
Alnylam Pharmaceuticals
Information provided by (Responsible Party):
Vir Biotechnology, Inc.

Brief Summary:

This is a phase 1/2 study in which healthy adult subjects and subjects with chronic hepatitis B virus (HBV) infection will receive VIR-2218 or placebo and will be assessed for safety, tolerability, pharmacokinetics, and antiviral activity (only in subjects with chronic HBV).

In the single ascending dose (SAD) part, Part A, healthy adult subjects will receive one dose of VIR-2218 or placebo, administered subcutaneously (SC). In the multiple ascending dose (MAD) parts, Part B & Part C, subjects with chronic HBV infection will receive two doses of VIR-2218 or placebo every 4 weeks administered SC.


Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: VIR-2218 Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of VIR-2218
Actual Study Start Date : November 14, 2018
Actual Primary Completion Date : September 3, 2020
Actual Study Completion Date : September 3, 2020


Arm Intervention/treatment
Experimental: Part A: SAD VIR-2218 50 mg
Healthy subjects received a single dose of VIR-2218 of 50 mg administered SC
Drug: VIR-2218
VIR-2218 given by subcutaneous injection

Experimental: Part A: SAD VIR-2218 100 mg
Healthy subjects received a single dose of VIR-2218 of 100 mg administered SC
Drug: VIR-2218
VIR-2218 given by subcutaneous injection

Experimental: Part A: SAD VIR-2218 200 mg
Healthy subjects received a single dose of VIR-2218 of 200 mg administered SC
Drug: VIR-2218
VIR-2218 given by subcutaneous injection

Experimental: Part A: SAD VIR-2218 400 mg
Healthy subjects received a single dose of VIR-2218 of 400 mg administered SC
Drug: VIR-2218
VIR-2218 given by subcutaneous injection

Experimental: Part A: SAD VIR-2218 600 mg
Healthy subjects received a single dose of VIR-2218 of 600 mg administered SC
Drug: VIR-2218
VIR-2218 given by subcutaneous injection

Experimental: Part A: SAD VIR-2218 900 mg
Healthy subjects received a single dose of VIR-2218 of 900 mg administered SC
Drug: VIR-2218
VIR-2218 given by subcutaneous injection

Placebo Comparator: Part A: SAD Placebo
Healthy subjects received a single dose of placebo administered SC
Drug: Placebo
Sterile normal saline (0.9% NaCl) given by subcutaneous injection

Experimental: Part B: MAD VIR-2218 20 mg
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 20 mg VIR-2218 administered 4 weeks apart.
Drug: VIR-2218
VIR-2218 given by subcutaneous injection

Experimental: Part B: MAD VIR-2218 50 mg
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.
Drug: VIR-2218
VIR-2218 given by subcutaneous injection

Experimental: Part B: MAD VIR-2218 100 mg
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 100 mg VIR-2218 administered 4 weeks apart.
Drug: VIR-2218
VIR-2218 given by subcutaneous injection

Experimental: Part B: MAD VIR-2218 200 mg
Chronic HBV, HBeAg negative, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.
Drug: VIR-2218
VIR-2218 given by subcutaneous injection

Experimental: Part C: MAD VIR-2218 50 mg
Chronic HBV, HBeAg positive, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.
Drug: VIR-2218
VIR-2218 given by subcutaneous injection

Experimental: Part C: MAD VIR-2218 200 mg
Chronic HBV, HBeAg positive, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.
Drug: VIR-2218
VIR-2218 given by subcutaneous injection

Placebo Comparator: Part B: MAD Placebo
Chronic HBV, HBeAg negative, subjects received 2 SC doses of placebo administered 4 weeks apart.
Drug: Placebo
Sterile normal saline (0.9% NaCl) given by subcutaneous injection

Placebo Comparator: Part C: MAD Placebo
Chronic HBV, HBeAg positive, subjects received 2 SC doses of placebo administered 4 weeks apart.
Drug: Placebo
Sterile normal saline (0.9% NaCl) given by subcutaneous injection




Primary Outcome Measures :
  1. Incidence of Adverse Events (AEs) [ Time Frame: Up to 364 days ]
    Number of Subjects with Adverse Events as assessed by CTCAE v5.0. In our planned analysis for this outcome measure, incidence is defined as the number of participants with treatment emergent AEs (TEAEs) in relation to the total number of participants in the cohort.

  2. Clinical Assessments Including But Not Limited to Laboratory Test Results [ Time Frame: Up to 336 days ]
    Number of participants with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0.


Secondary Outcome Measures :
  1. Maximum Plasma Concentration (ng/mL) [ Time Frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5 ]
    VIR-2218 and metabolite Maximum Concentration in Plasma

  2. Time to Reach Maximum Plasma Concentration (h) [ Time Frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5 ]
    VIR-2218 and metabolite time of Cmax in Plasma: Median (Inter-Quartile Range Q1-Q3)

  3. Area Under the Plasma Concentration Versus Time Curve (ng*h/mL) [ Time Frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1; Part B/C: predose on Day 1 and at 1h, 2h, 4h, 8h, 24h postdose, Week 1, predose on Week 4 and at 1h, 2h, 4h, 8h, 24h postdose, and Week 5 ]
    VIR-2218 and metabolite Area under the curve from time 0 to last measurable Time

  4. Apparent Terminal Elimination Half-life (h) [ Time Frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose and Week 1 ]
    VIR-2218 Apparent Elimination Half-life t1/2 in Plasma: Median (Inter-Quartile Range Q1-Q3)

  5. Apparent Plasma Clearance (L/h) [ Time Frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1 ]
    VIR-2218 CL/F Apparent plasma clearance

  6. Apparent Volume of Distribution (L) [ Time Frame: Part A: predose on Day 1 and at 30 min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 48h postdose, and Week 1 ]
    VIR-2218 VZ/F apparent volume of distribution

  7. Urine %fe 0-24h [ Time Frame: Pooled urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs) ]
    VIR-2218 and metabolite: Fraction excreted in the urine from time 0 to 24 h. Pooled Urine PK samples was collected at pre-specified intervals in the single ascending dose study of VIR-2218. Therefore, the following PK parameter, fraction excreted in the urine ( %fe 0-24h ) was only calculated in healthy subjects who participated in Part A of the study. This parameter was not listed as a secondary endpoint for parts B/C in the submitted protocol, and as such was not reported in this secondary outcome measures.

  8. Apparent Renal Clearance (CLR/F) [ Time Frame: Pooled Urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs) ]
    VIR-2218 Apparent renal clearance from 0 to 24 h. Pooled Urine PK samples was collected at pre-specified intervals in the single ascending dose study of VIR-2218. Therefore, the following PK parameter, apparent renal clearance (CLR/F) was only calculated in healthy subjects who participated in Part A of the study. This parameter was not listed as a secondary endpoint for parts B/C in the submitted protocol, and as such was not reported in this secondary outcome measures.

  9. Maximum Reduction of Serum HBsAg From Baseline [ Time Frame: Up to 112 days ]
    Maximum reduction of serum HBsAg from Day 1 until Week 16.

  10. Number of Subjects With Serum HBsAg Loss at Any Time Point [ Time Frame: Up to 336 days ]
    Serum HBsAg loss is defined as quantitative HBsAg < 0.05 IU/mL at two or more consecutive measurements

  11. Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months [ Time Frame: Up to 336 days ]
    Serum HBsAg loss is defined as quantitative HBsAg < 0.05 IU/mL at two or more consecutive measurements

  12. Number of Subjects With Anti-HBs Seroconversion at Any Timepoint [ Time Frame: Up to 336 days ]
    Anti-HBs seroconversion is defined as anti-HBs positivity at two or more consecutive measurements

  13. Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint [ Time Frame: Up to 336 days ]
    HBeAg loss is defined as quantitative HBeAg < 0.11 IU/mL at two or more consecutive measurements. anti-HBe seroconversion is defined as anti-HBe positivity at two or more consecutive measurements



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Part A SAD:

Inclusion Criteria:

  • Male or female age 18 - 55
  • BMI 18 - 32 kg/m^2

Exclusion Criteria:

  • Any clinically significant chronic or acute medical condition that makes the volunteer unsuitable for participation
  • History or evidence of drug or alcohol abuse
  • History of intolerance to SC injection

Parts B/C MAD:

Inclusion Criteria:

  • Male or female age 18 - 65
  • BMI 18 - 32 kg/m^2
  • Chronic HBV infection for >/= 6 months

Exclusion Criteria:

  • Any clinically significant chronic or acute medical condition that makes the volunteer unsuitable for participation
  • Significant fibrosis or cirrhosis
  • History or evidence of drug or alcohol abuse
  • History of intolerance to SC injection
  • History of chronic liver disease from any cause other than chronic HBV infection
  • History of hepatic decompensation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03672188


Locations
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Australia, Queensland
Investigative Site
Birtinya, Queensland, Australia, 4575
Australia, Victoria
Investigative Site
Clayton, Victoria, Australia, 3168
Investigative Site
Fitzroy, Victoria, Australia, 3065
Hong Kong
Investigative Site
Hong Kong, Hong Kong
Korea, Republic of
Investigative Site
Busan, Korea, Republic of, 49241
Investigative Site
Seoul, Korea, Republic of, 03080
Investigative Site
Seoul, Korea, Republic of, 05505
New Zealand
Investigative Site
Auckland, New Zealand, 1010
Investigative Site
Auckland, New Zealand, 2025
Thailand
Investigative Site
Bangkok, Thailand, 10330
Investigative Site
Bangkok, Thailand, 10400
Investigative Site
Bangkok, Thailand, 10700
Investigative Site
Hat Yai, Thailand, 90110
Investigative Site
Khon Kaen, Thailand, 40002
Sponsors and Collaborators
Vir Biotechnology, Inc.
Alnylam Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Vir Biotechnology, Inc.:
Study Protocol  [PDF] March 27, 2019
Statistical Analysis Plan  [PDF] December 22, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Vir Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT03672188    
Other Study ID Numbers: VIR-2218-1001
First Posted: September 14, 2018    Key Record Dates
Results First Posted: December 13, 2021
Last Update Posted: December 13, 2021
Last Verified: December 2021

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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:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Infections
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
Hepadnaviridae Infections
DNA Virus Infections