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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

VIR-2218

Placebo

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Part A: SAD VIR-2218 50 mg

Part A: SAD VIR-2218 100 mg

Part A: SAD VIR-2218 200 mg

Part A: SAD VIR-2218 400 mg

Part A: SAD VIR-2218 600 mg

Part A: SAD VIR-2218 900 mg

Part A: SAD Placebo

Part B: MAD VIR-2218 20 mg

Part B: MAD VIR-2218 50 mg

Part B: MAD VIR-2218 100 mg

Part B: MAD VIR-2218 200 mg

Part C: MAD VIR-2218 50 mg

Part C: MAD VIR-2218 200 mg

Part B: MAD Placebo

Part C: MAD Placebo

Arm Description

Healthy subjects received a single dose of VIR-2218 of 50 mg administered SC

Healthy subjects received a single dose of VIR-2218 of 100 mg administered SC

Healthy subjects received a single dose of VIR-2218 of 200 mg administered SC

Healthy subjects received a single dose of VIR-2218 of 400 mg administered SC

Healthy subjects received a single dose of VIR-2218 of 600 mg administered SC

Healthy subjects received a single dose of VIR-2218 of 900 mg administered SC

Healthy subjects received a single dose of placebo administered SC

Chronic HBV, HBeAg negative, subjects received 2 SC doses of 20 mg VIR-2218 administered 4 weeks apart.

Chronic HBV, HBeAg negative, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.

Chronic HBV, HBeAg negative, subjects received 2 SC doses of 100 mg VIR-2218 administered 4 weeks apart.

Chronic HBV, HBeAg negative, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.

Chronic HBV, HBeAg positive, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.

Chronic HBV, HBeAg positive, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.

Chronic HBV, HBeAg negative, subjects received 2 SC doses of placebo administered 4 weeks apart.

Chronic HBV, HBeAg positive, subjects received 2 SC doses of placebo administered 4 weeks apart.

Outcomes

Primary Outcome Measures

Incidence of Adverse Events (AEs)

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.

Clinical Assessments Including But Not Limited to Laboratory Test Results

Number of participants with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0.

Secondary Outcome Measures

Maximum Plasma Concentration (ng/mL)

VIR-2218 and metabolite Maximum Concentration in Plasma

Time to Reach Maximum Plasma Concentration (h)

VIR-2218 and metabolite time of Cmax in Plasma: Median (Inter-Quartile Range Q1-Q3)

Area Under the Plasma Concentration Versus Time Curve (ng*h/mL)

VIR-2218 and metabolite Area under the curve from time 0 to last measurable Time

Apparent Terminal Elimination Half-life (h)

VIR-2218 Apparent Elimination Half-life t1/2 in Plasma: Median (Inter-Quartile Range Q1-Q3)

Apparent Plasma Clearance (L/h)

VIR-2218 CL/F Apparent plasma clearance

Apparent Volume of Distribution (L)

VIR-2218 VZ/F apparent volume of distribution

Urine %fe 0-24h

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.

Apparent Renal Clearance (CLR/F)

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.

Maximum Reduction of Serum HBsAg From Baseline

Maximum reduction of serum HBsAg from Day 1 until Week 16.

Number of Subjects With Serum HBsAg Loss at Any Time Point

Serum HBsAg loss is defined as quantitative HBsAg < 0.05 IU/mL at two or more consecutive measurements

Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months

Serum HBsAg loss is defined as quantitative HBsAg < 0.05 IU/mL at two or more consecutive measurements

Number of Subjects With Anti-HBs Seroconversion at Any Timepoint

Anti-HBs seroconversion is defined as anti-HBs positivity at two or more consecutive measurements

Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint

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

Full Information

NCT ID

NCT03672188

First Posted

September 11, 2018

Last Updated

December 9, 2021

Sponsor

Vir Biotechnology, Inc.

Collaborators

Alnylam Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03672188

Brief Title

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

Official Title

A Phase 1/2, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of VIR-2218

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

November 14, 2018 (Actual)

Primary Completion Date

September 3, 2020 (Actual)

Study Completion Date

September 3, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vir Biotechnology, Inc.

Collaborators

Alnylam Pharmaceuticals

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis B

Keywords

Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

82 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A: SAD VIR-2218 50 mg

Arm Type

Experimental

Arm Description

Healthy subjects received a single dose of VIR-2218 of 50 mg administered SC

Arm Title

Part A: SAD VIR-2218 100 mg

Arm Type

Experimental

Arm Description

Healthy subjects received a single dose of VIR-2218 of 100 mg administered SC

Arm Title

Part A: SAD VIR-2218 200 mg

Arm Type

Experimental

Arm Description

Healthy subjects received a single dose of VIR-2218 of 200 mg administered SC

Arm Title

Part A: SAD VIR-2218 400 mg

Arm Type

Experimental

Arm Description

Healthy subjects received a single dose of VIR-2218 of 400 mg administered SC

Arm Title

Part A: SAD VIR-2218 600 mg

Arm Type

Experimental

Arm Description

Healthy subjects received a single dose of VIR-2218 of 600 mg administered SC

Arm Title

Part A: SAD VIR-2218 900 mg

Arm Type

Experimental

Arm Description

Healthy subjects received a single dose of VIR-2218 of 900 mg administered SC

Arm Title

Part A: SAD Placebo

Arm Type

Placebo Comparator

Arm Description

Healthy subjects received a single dose of placebo administered SC

Arm Title

Part B: MAD VIR-2218 20 mg

Arm Type

Experimental

Arm Description

Chronic HBV, HBeAg negative, subjects received 2 SC doses of 20 mg VIR-2218 administered 4 weeks apart.

Arm Title

Part B: MAD VIR-2218 50 mg

Arm Type

Experimental

Arm Description

Chronic HBV, HBeAg negative, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.

Arm Title

Part B: MAD VIR-2218 100 mg

Arm Type

Experimental

Arm Description

Chronic HBV, HBeAg negative, subjects received 2 SC doses of 100 mg VIR-2218 administered 4 weeks apart.

Arm Title

Part B: MAD VIR-2218 200 mg

Arm Type

Experimental

Arm Description

Chronic HBV, HBeAg negative, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.

Arm Title

Part C: MAD VIR-2218 50 mg

Arm Type

Experimental

Arm Description

Chronic HBV, HBeAg positive, subjects received 2 SC doses of 50 mg VIR-2218 administered 4 weeks apart.

Arm Title

Part C: MAD VIR-2218 200 mg

Arm Type

Experimental

Arm Description

Chronic HBV, HBeAg positive, subjects received 2 SC doses of 200 mg VIR-2218 administered 4 weeks apart.

Arm Title

Part B: MAD Placebo

Arm Type

Placebo Comparator

Arm Description

Chronic HBV, HBeAg negative, subjects received 2 SC doses of placebo administered 4 weeks apart.

Arm Title

Part C: MAD Placebo

Arm Type

Placebo Comparator

Arm Description

Chronic HBV, HBeAg positive, subjects received 2 SC doses of placebo administered 4 weeks apart.

Intervention Type

Drug

Intervention Name(s)

VIR-2218

Intervention Description

VIR-2218 given by subcutaneous injection

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Sterile normal saline (0.9% NaCl) given by subcutaneous injection

Primary Outcome Measure Information:

Title

Incidence of Adverse Events (AEs)

Description

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.

Time Frame

Up to 364 days

Title

Clinical Assessments Including But Not Limited to Laboratory Test Results

Description

Number of participants with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0.

Time Frame

Up to 336 days

Secondary Outcome Measure Information:

Title

Maximum Plasma Concentration (ng/mL)

Description

VIR-2218 and metabolite Maximum Concentration in Plasma

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

Title

Time to Reach Maximum Plasma Concentration (h)

Description

VIR-2218 and metabolite time of Cmax in Plasma: Median (Inter-Quartile Range Q1-Q3)

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

Title

Area Under the Plasma Concentration Versus Time Curve (ng*h/mL)

Description

VIR-2218 and metabolite Area under the curve from time 0 to last measurable Time

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

Title

Apparent Terminal Elimination Half-life (h)

Description

VIR-2218 Apparent Elimination Half-life t1/2 in Plasma: Median (Inter-Quartile Range Q1-Q3)

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

Title

Apparent Plasma Clearance (L/h)

Description

VIR-2218 CL/F Apparent plasma clearance

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

Title

Apparent Volume of Distribution (L)

Description

VIR-2218 VZ/F apparent volume of distribution

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

Title

Urine %fe 0-24h

Description

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.

Time Frame

Pooled urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs)

Title

Apparent Renal Clearance (CLR/F)

Description

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.

Time Frame

Pooled Urine was collected at time interval D1 (0-4 hrs) (4-8 hrs) (8-12 hrs) and (12-24 hrs)

Title

Maximum Reduction of Serum HBsAg From Baseline

Description

Maximum reduction of serum HBsAg from Day 1 until Week 16.

Time Frame

Up to 112 days

Title

Number of Subjects With Serum HBsAg Loss at Any Time Point

Description

Serum HBsAg loss is defined as quantitative HBsAg < 0.05 IU/mL at two or more consecutive measurements

Time Frame

Up to 336 days

Title

Number of Subjects With Sustained Serum HBsAg Loss for >/= 6 Months

Description

Serum HBsAg loss is defined as quantitative HBsAg < 0.05 IU/mL at two or more consecutive measurements

Time Frame

Up to 336 days

Title

Number of Subjects With Anti-HBs Seroconversion at Any Timepoint

Description

Anti-HBs seroconversion is defined as anti-HBs positivity at two or more consecutive measurements

Time Frame

Up to 336 days

Title

Number of Subjects With HBeAg Loss and/or Anti-HBe Seroconversion at Any Timepoint

Description

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

Time Frame

Up to 336 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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

Facility Information:

Facility Name

Investigative Site

City

Birtinya

State/Province

Queensland

ZIP/Postal Code

4575

Country

Australia

Facility Name

Investigative Site

City

Clayton

State/Province

Victoria

ZIP/Postal Code

3168

Country

Australia

Facility Name

Investigative Site

City

Fitzroy

State/Province

Victoria

ZIP/Postal Code

3065

Country

Australia

Facility Name

Investigative Site

City

Hong Kong

Country

Hong Kong

Facility Name

Investigative Site

City

Busan

ZIP/Postal Code

49241

Country

Korea, Republic of

Facility Name

Investigative Site

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

Facility Name

Investigative Site

City

Seoul

ZIP/Postal Code

05505

Country

Korea, Republic of

Facility Name

Investigative Site

City

Auckland

ZIP/Postal Code

1010

Country

New Zealand

Facility Name

Investigative Site

City

Auckland

ZIP/Postal Code

2025

Country

New Zealand

Facility Name

Investigative Site

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

Facility Name

Investigative Site

City

Bangkok

ZIP/Postal Code

10400

Country

Thailand

Facility Name

Investigative Site

City

Bangkok

ZIP/Postal Code

10700

Country

Thailand

Facility Name

Investigative Site

City

Hat Yai

ZIP/Postal Code

90110

Country

Thailand

Facility Name

Investigative Site

City

Khon Kaen

ZIP/Postal Code

40002

Country

Thailand

12. IPD Sharing Statement

Citations:

PubMed Identifier

34741731

Citation

Gupta SV, Fanget MC, MacLauchlin C, Clausen VA, Li J, Cloutier D, Shen L, Robbie GJ, Mogalian E. Clinical and Preclinical Single-Dose Pharmacokinetics of VIR-2218, an RNAi Therapeutic Targeting HBV Infection. Drugs R D. 2021 Dec;21(4):455-465. doi: 10.1007/s40268-021-00369-w. Epub 2021 Nov 6.

Results Reference

derived

Chronic Hepatitis B

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial