Clinical Trials Register

Summary
EudraCT Number:	2019-004212-64
Sponsor's Protocol Code Number:	IMC-I109V-101
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2020-06-11
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2019-004212-64

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Phase 1/2 study of IMC-I109V in non-cirrhotic HBeAg-negative chronic HBV infection

A.3.2

Name or abbreviated title of the trial where available

IMC-I109V-101

A.4.1

Sponsor's protocol code number

IMC-I109V-101

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Immunocore Ltd
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Immunocore Ltd
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Immunocore Ltd
B.5.2	Functional name of contact point	Sheetal Thakur
B.5.3	Address:
B.5.3.1	Street Address	92 Park Drive Milton Park
B.5.3.2	Town/ city	Abingdon
B.5.3.3	Post code	OX14 4RY
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+1 267 3007657
B.5.6	E-mail	sheetal.thakur@immunocore.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	IMC-I109V
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	N/A
D.3.9.2	Current sponsor code	IMC-I109V
D.3.9.3	Other descriptive name	IMC-I109V
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

chronic hepatitis B virus (HBV) infection

E.1.1.1

Medical condition in easily understood language

chronic hepatitis B virus (HBV) infection

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10019182
E.1.2	Term	HBV
E.1.2	System Organ Class	100000004848

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10019743
E.1.2	Term	Hepatitis B virus (HBV)
E.1.2	System Organ Class	100000004848

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary (Part 1 – SAD)
To evaluate the safety and tolerability of IMC-I109V when administered as a single dose in virally suppressed, HBeAg-negative participants

Primary (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, HBeAgmnegative participants

E.2.2

Secondary objectives of the trial

1) To characterize the PK profile of IMC-I109V in single dose and multiple dose schedules
2) To evaluate incidence of anti-IMC-I109V antibody formations following single and multiple infusions
3) To assess the antiviral effects of IMC-I109V following administration of SAD and MAD schedules using HBV biomarkers

E.2.3

Trial contains a sub-study

E.3

Principal 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 >3 months prior to the screening visit available for review.
5. Have been receiving entecavir and/or tenofovir (including tenofovir alafenamide) for ≥ 12 months prior to screening and are willing to continue.
6. HBV DNA negative (below the LLOQ) at screening
7. Quantitative HBV surface antigen ≤ 1000 IU/mL at the screening visit.
Participants with HBsAg levels ≥ 1000 IU/mL and ≤ 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:
a. Liver biopsy demonstrating a Metavir Fibrosis Score of F0-2 (or equivalent);
OR
b. Fibroscan® result of < 9 kPa.
NOTE: A confirmatory Fibroscan® is required within 6 months prior to Day 1.
9. Liver imaging confirming absence of clinically significant abnormalities is required within 6 months prior to Day 1.
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 3 months after the final dose of the study intervention or longer if required by local regulations; cessation of birth control after this point should be discussed with a responsible physician. *Male participants are not allowed to donate sperm from the time of enrollment until 3 months post-administration of study interventions or longer if required by local
regulations.
*Female participants must refrain from egg donation during the course of the study
11. Capable of giving signed informed consent

E.4

Principal exclusion criteria

Medical Conditions
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 ≤ 3 years prior to the screening visit (except adequately treated carcinoma in situ and basal cell carcinoma of the skin). NOTE: Participants under evaluation for malignancy are not eligible
9. Known or suspected hypersensitivity or previous severe reactions to any of the constituents of IMC-I109V, or the drugs used in the pretreatment regimen (eg, dexamethasone, ibuprofen and paracetamol)
10. Pregnant or lactating women

Prior/Concomitant Therapy
11. Receiving or planning to receive systemic immunosuppressive medications during the study or ≤ 2 months prior to Day 1, including but not limited to prednisone > 10 mg/day (or equivalent), methotrexate, cyclosporine, or interferon. NOTE: Local steroid therapy are allowed (eg,inhaled, otic, ophthalmic, or intra-articular medications).

Prior/Concurrent Clinical Study Experience
12. Use of any live vaccines against infectious diseases within 4 weeks of the first planned administration of study intervention or use of any non-live vaccines against infectious diseases within 2 weeks of the first planned administration of study intervention.
13. Treatment with any investigational drug or enrollment in any other clinical study ≤ 6 months prior to Day 1, or at any time during participation in the study
Laboratory Exclusion Criteria
14. If any of the laboratory exclusion criteria are met, then the site may have the participant retested. If a single value is within ±10% of the listed laboratory exclusion criterion value upon retest, and the value is considered to be not clinically significant by the physician investigator, the participant may be considered for enrollment.

Other Exclusions
15. Clinical diagnosis of substance abuse with alcohol, narcotics, or cocaine ≤ 12 months prior to the screening visit, except for those participants monitored in an opioid substitution maintenance program
16. Poor venous access that precludes routine peripheral blood sampling or intravenous (IV) infusion required for this study
17. Participants who have a planned need for anesthesia for outpatient surgery or any other reasons during the study
18. Employed as site personnel directly involved with this study

E.5 End points

E.5.1

Primary end point(s)

• Incidence and severity of treatment-emergent adverse events (TEAEs)
• Incidence of dose-limiting toxicities (DLTs)
• Changes in safety laboratory parameters, vital signs, and electrocardiogram (QTcF)
• Incidence of serious adverse events (SAEs)
• Incidence of adverse events (AEs) leading to treatment discontinuation
Through 28 days after the last infusion of study treatment

E.5.1.1

Timepoint(s) of evaluation of this end point

Through 28 days after the last infusion of study treatment

E.5.2

Secondary end point(s)

IMC-I109V serum PK parameters (eg, AUC, Cmax, Tmax, t1/2) after single and multiple doses
Incidence of anti-IMC-I109V antibody formation following administration of 1 or more doses of study drug
HBsAg, hepatitis core-related antigen (HBcrAg), HBV RNA, HBsAb changes from baseline through end of trial

E.5.2.1

Timepoint(s) of evaluation of this end point

-IMC-I109V serum PK parameters (eg, AUC, Cmax, Tmax, t1/2) after single and multiple doses
- Incidence of anti-IMC-I109V antibody formation following administration of 1 or more doses of study drug
SAD – W1D1 and W4D1
MAD - pre-dose (dose 1, dose 3, dose 5, dose 16 and EOT (last dose) and Follow-up Week 24 (last FU week)
- HBsAg, hepatitis B core-related antigen (HBcrAg), HBV RNA, HBsAb changes from baseline through end of trial
SAD – W1D1, W1D3, W2D1, W3D1, W4D1, W5D1
MAD - performed weekly Week 1-Week 8, then every 4 weeks during Week 8-Week 24

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Belgium

Hong Kong

Korea, Republic of

New Zealand

Poland

Romania

Spain

Ukraine

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1