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Trial registered on ANZCTR


Registration number
ACTRN12620000403932p
Ethics application status
Submitted, not yet approved
Date submitted
5/03/2020
Date registered
25/03/2020
Date last updated
25/03/2020
Date data sharing statement initially provided
25/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase 1/2 study of IMC-I109V in non-cirrhotic HBeAg-negative chronic hepatitis B (HBV) infection
Scientific title
An Open-label Study Evaluating the Safety, Antiviral Activity, and Pharmacokinetics of IMC-I109V in HLA-A*02:01 Positive Patients with Chronic HBV who are Non-Cirrhotic, Hepatitis B e Antigen-negative, and Virally Suppressed
Secondary ID [1] 300363 0
IMC-I109V-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HBeAg-negative chronic HBV infection 315974 0
Condition category
Condition code
Infection 314251 314251 0 0
Other infectious diseases
Oral and Gastrointestinal 314988 314988 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
The purpose of this study is to test IMCI109V in people with chronic hepatitis B virus (HBV) infection and to assess the safety and effectiveness a new treatment, called IMC-I109V. IMC- I109V has been developed to treat HBV by activating the body’s own immune system to fight the virus. This is the first time that IMC-I109V is being tested in humans. The study consists of 2 parts as follows;
Part 1 – Single Ascending Dose (SAD): will be approximately 10 weeks for each participant, comprising a maximum 42-day screening period, a 1-day treatment period involving a single administration of IMC-I109V (by intravenous (IV) infusion) and a 28 day follow-up period, for a total of 9 visits. The first cohort will receive a single IMC-I109V starting dose of 0.8 mcg, and subsequent cohorts up to 60.0 mcg. Visits will take place on Day -1 and Days 1, 2, 3, 5, 8, 15, 22, and 29. Follow up may be extended in participants who achieve a decrease in HBsAg of greater than 0.5 log10 IU/mL at Day 29. Approximately 5 to 9 cohorts will be enrolled.

Part 2 – Multiple Ascending Dose (MAD): will be approximately 54 weeks for each participant, comprising a maximum 42-day screening period, a 24-week treatment period involving weekly administration of IMC-I109V (by intravenous (IV) infusion), and a 24-week follow-up period, with a total of 30 visits. The initial dose in Part 2 – MAD will be the lowest dose evaluated during Part 1 – SAD i.e. 0.8 mcg. Visits will take place on Day -1 and Days 1, 3, 5, and 8, Weeks 3 (Day 15) through 24, Weeks 28, 36, 48 and 49. Participants who have achieved HBsAg less than 100 IU/mL at end of Week 24 may be considered for further study treatments of up to Week 48 and follow-up visits every 12 weeks to Week 72. Treatment will be discontinued at Week 16 in participants who have not shown evidence of a response to IMC-I109V. Approximately 3 to 6 dose cohorts will be enrolled and the maximum possible dose that may be administered to a cohort will be 60.0 mcg.
The participant groups in SAD and MAD are exclusive.
Intervention code [1] 316641 0
Treatment: Drugs
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 322635 0
(Part 1 – SAD) To evaluate the safety and tolerability of IMC-I109V when administered as a single dose in virally suppressed, HBeAg-negative participants.
Timepoint [1] 322635 0
Assessed through 28 days after the last infusion of study treatment.
Parameters:
1. Incidence and severity of treatment-emergent adverse events (TEAEs)
2. Incidence of dose-limiting toxicities (DLTs)
3. Changes in safety laboratory parameters, vital signs, and electrocardiogram (QTcF),
4. Incidence of serious adverse events (SAEs)
5. Incidence of adverse events (AEs) leading to treatment discontinuation
Primary outcome [2] 322636 0
(Part 2 – MAD) To evaluate the safety and tolerability of IMC-I109V when administered in a multiple dose schedule up to week 24 in virally suppressed, HBeAg-negative participants
Timepoint [2] 322636 0
Assessed through 28 days after the last infusion of study treatment.
Parameters:
1. Incidence and severity of treatment-emergent adverse events (TEAEs)
2. Incidence of dose-limiting toxicities (DLTs)
3. Changes in safety laboratory parameters, vital signs, and electrocardiogram (QTcF),
4. Incidence of serious adverse events (SAEs)
5. Incidence of adverse events (AEs) leading to treatment discontinuation
Secondary outcome [1] 379135 0
To characterize the pharmacokinetic (PK) profile of IMC-I109V in single dose and multiple dose schedules
Timepoint [1] 379135 0
Assessed through 3 days after the last infusion of study treatment.
IMC-I109V serum PK parameters (eg, AUC, Cmax, Tmax, t1/2) after single and multiple doses will determine the endpoints for this secondary outcome.
IMC-I109V PK samples collection timepoints in Part 1 - SAD: pre-dose (within 2 hours of start of infusion), End of Infusion(EOI), 2 hours post-EOI, 4 hours post-EOI, 8 hours post-EOI, 12 hour post-EOI, 24 hours post-EOI, then Day 3 (48 hours post-EOI).
IMC-I109V PK samples collection timepoints in Part 2 - MAD: Dose L1 - pre-dose (within 2 hours), EOI, 2 hours post-EOI, 4 hours post-EOI, 8 hours post-EOI, 12 hours post-EOI, 24 hours post-EOI, then Day 3 (48 hours post-EOI);
Dose T1 - pre-dose (within 2 hours), EOI, 2 hours post-EOI, 4 hours post- EOI, 8 hours post-EOI;
Doses T2 – T24 - pre-dose (within 2 hours), EOI.
Secondary outcome [2] 379138 0
To evaluate incidence of anti-IMC-I109V antibody formations following single and multiple infusions.
This outcome is analysed by Anti-Drug-Antibody(ADA) Analysis.
Timepoint [2] 379138 0
Incidence of anti-IMC-I109V antibody formation following administration of 1 or more doses of study drug will determine the endpoint for this secondary outcome.

IMC-I109V Anti-Drug Antibody(ADA) will be assessed through each infusion of study treatment and EOT.
IMC-I109V Anti-Drug Antibody(ADA) samples will be collected pre-dose during Part 1 - SAD. During Part 2 - MAD, the ADA samples will be collected pre-dose (dose 1, dose 3, dose 5, dose 16 and EOT (last dose) and Follow-up Week 24 (last FU week)
Secondary outcome [3] 379139 0
To assess the antiviral effects of IMC-I109V following administration of SAD and MAD schedules using HBV biomarkers
This outcome is analysed by HBsAg, hepatitis B core-related antigen (HBcrAg), HBV RNA, HBsAb analysis.
Timepoint [3] 379139 0
Evaluation of HBsAg, hepatitis B core-related antigen (HBcrAg), HBV RNA, HBsAb changes from baseline through end of trial will assess the antiviral effects of IMC-I109V following administration of SAD and MAD schedules.
Samples for quantification of HBsAg, HBV RNA, hepatitis B core-related antigen (HBcrAg) and HBsAb will be collected at following timepoints;
Part 1 - SAD: Day 1(predose), Day 3, Follow-up Week 2, 3, 4 and 5.
Part 2 - MAD: Will be performed weekly Week 1-Week 8, then every 4 weeks during Week 8-Week 24


Eligibility
Key inclusion criteria
1. Aged 18 to 55 years inclusive, at the time of signing the informed consent.
2. HLA-A*02:01 positive (central laboratory testing)
3. Documented evidence of CHB based on one of the following:
a. Positive HBsAg and HBV DNA at least 6 months prior to the screening visit; OR
b. Historical liver biopsy consistent with CHB infection available.
4. If previously HBeAg-positive, participants must be HBeAg-negative at the screening
visit and have historical HBeAg-negative status greater than 3 months prior to the screening visit available for review.
5. Have been receiving entecavir and/or tenofovir (including tenofovir alafenamide) for
greater than or equal to 12 months prior to screening and are willing to continue.
6. HBV DNA negative at screening.
7. Quantitative HBV surface antigen less than or equal to 1000 IU/mL at the screening visit. Participants with HBsAg levels greater than or equal to 1000 IU/mL and less than or equal to 3000 IU/mL may be eligible after consultation with, and approval by, the Sponsor’s Medical Monitor.
8. All participants must have no history of liver cirrhosis AND prior assessment of fibrosis demonstrating non-cirrhotic status at screening. as defined by one of the following:
9. a. Liver biopsy demonstrating a Metavir Fibrosis Score of F0-2 (or equivalent);
OR
b. Fibroscan® result of less than 9 kPa.
10. Male and female participants of childbearing potential who are sexually active with a nonsterilized partner must agree to use highly effective methods of birth control from the trial screening date until 6 months after the final dose of the study intervention.
11. Capable of giving signed informed consent.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants are excluded from the study if ANY of the following criteria apply:
1. Known co-infection with any of the following:
a. HIV
b. Hepatitis C virus OR
c. Hepatitis D virus
2. Changes in HBeAg status within 3 months prior to the screening visit.
3. Known HBV genotype A
4. History of HCC
5. Gilbert’s syndrome
6. Any known pre-existing medical or psychiatric condition that could interfere with the participant’s ability to provide informed consent or participate in study conduct, or that may confound study findings.
7. Significant immunosuppression from, but not limited to immunodeficiency conditions
such as common variable hypogammaglobulinemia.
8. Evidence of active or suspected malignancy, or a history of malignancy less than or equal to 3 years prior to the screening visit (except adequately treated carcinoma in situ and basal cell carcinoma of the skin).
9. Known or suspected hypersensitivity or previous severe reactions to any of the constituents of IMC-I109V, or the drugs used in the pre-treatment regimen (eg, dexamethasone, ibuprofen and paracetamol).
10. Pregnant or lactating women.


Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Part 1 - SAD: Approximately, 20 to 36 participants will be enrolled in approximately 5 to 9 ascending dose cohorts, with a minimum of 4 participants per cohort.

Part 2 - MAD: A total of approximately 28 to 44 participants will be enrolled into approximately 3 to 6 dose cohorts, with a minimum of 4 participants each.
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment hospital [1] 15683 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 15684 0
Nepean Hospital - Kingswood
Recruitment hospital [3] 15685 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [4] 15686 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 29102 0
3065 - Fitzroy
Recruitment postcode(s) [2] 29103 0
2747 - Kingswood
Recruitment postcode(s) [3] 29104 0
6009 - Nedlands
Recruitment postcode(s) [4] 29105 0
2010 - Darlinghurst
Recruitment outside Australia
Country [1] 22260 0
New Zealand
State/province [1] 22260 0
Country [2] 22261 0
Hong Kong
State/province [2] 22261 0
Country [3] 22262 0
Moldova, Republic Of
State/province [3] 22262 0
Country [4] 22263 0
United Kingdom
State/province [4] 22263 0
Country [5] 22264 0
Korea, Republic Of
State/province [5] 22264 0
Country [6] 22265 0
Romania
State/province [6] 22265 0
Country [7] 22266 0
Belgium
State/province [7] 22266 0
Country [8] 22267 0
Poland
State/province [8] 22267 0
Country [9] 22268 0
Spain
State/province [9] 22268 0

Funding & Sponsors
Funding source category [1] 304788 0
Commercial sector/Industry
Name [1] 304788 0
Immunocore Ltd
Address [1] 304788 0
101 Park Drive
Milton Park
Abingdon
Oxfordshire
OX14 4RY
United Kingdom
Country [1] 304788 0
United Kingdom
Primary sponsor type
Commercial sector/Industry
Name
Immunocore Ltd
Address
101 Park Drive
Milton Park
Abingdon
Oxfordshire
OX14 4RY
United Kingdom
Country
United Kingdom
Secondary sponsor category [1] 305105 0
None
Name [1] 305105 0
NA
Address [1] 305105 0
NA
Country [1] 305105 0
Other collaborator category [1] 281147 0
Commercial sector/Industry
Name [1] 281147 0
Novotech (Australia) Pty Limited
Address [1] 281147 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 281147 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305202 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 305202 0
St. Vincent’s Hospital Melbourne
Research Governance Unit (RGU), PO Box 2900
Fitzroy, 3065, VIC, Australia
Ethics committee country [1] 305202 0
Australia
Date submitted for ethics approval [1] 305202 0
28/01/2020
Approval date [1] 305202 0
Ethics approval number [1] 305202 0

Summary
Brief summary
Hepatitis B is the most common liver infection in the world and is caused by the hepatitis B virus (HBV). HBV enters the body and travels to the liver via the bloodstream. In the liver, the virus attaches to healthy liver cells and multiplies. The liver is the main site of HBV replication. Hepatitis B infection can lead to cirrhosis (scarring of the liver), liver cancer, or liver failure, if it is not diagnosed and managed appropriately. The purpose of this study is to test IMC-I109V in people with chronic hepatitis B virus (HBV) infection. The main goal of the study is to assess the safety and effectiveness a new treatment, called IMC-I109V. IMC- I109V has been developed to treat HBV by activating the body’s own immune system to fight the virus.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99594 0
Prof Alex Thompson
Address 99594 0
St. Vincent’s Hospital Melbourne
41 Victoria Parade
Fitzroy VIC 3065
Country 99594 0
Australia
Phone 99594 0
+61 0392313581
Fax 99594 0
Email 99594 0
alexander.thompson@svhm.org.au
Contact person for public queries
Name 99595 0
Dr Mudassar Mor
Address 99595 0
Novotech Australia Pty Ltd.
Level 3, 235 Pyrmont St Pyrmont NSW 2009 Australia
Country 99595 0
Australia
Phone 99595 0
+61 285691402
Fax 99595 0
Email 99595 0
Mudassar.Mor@novotech-cro.com
Contact person for scientific queries
Name 99596 0
Dr Mudassar Mor
Address 99596 0
Novotech Australia Pty Ltd.
Level 3, 235 Pyrmont St Pyrmont NSW 2009 Australia
Country 99596 0
Australia
Phone 99596 0
+61 285691402
Fax 99596 0
Email 99596 0
Mudassar.Mor@novotech-cro.com

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 other documents available
Summary results
No Results