Phase 1/2 study of IMC-M113V in virologically suppressed chronic HIV infection

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Immunocore Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

6 Apr 2022 → ongoing

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-513938-38-00

EudraCT number

2021-002008-11

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Pharmacokinetic

Part 1: Single Ascending Dose (SAD) Study
To evaluate the safety and tolerability of IMC-M113V when administered as a single dose during antiretroviral therapy (ART)
Part 2: Multiple Ascending Dose (MAD) Study
• To evaluate the safety and tolerability of IMC-M113V when administered in a multiple dose schedule, up to at least week 12, in participants receiving ART

Secondary objectives 5

1. To characterise the pharmacokinetic (PK) profile of IMC-M113V in single dose and multiple dose schedules.
2. To evaluate incidence of anti-IMC-M113V antibody formation following single and multiple infusions
3. To determine pharmacodynamic (PD) changes in the systemic immune response in relation to treatment with IMC-M113V, including but not limited to changes in peripheral cytokines and lymphocyte counts
4. To determine the incidence and duration of post-treatment control during analytical therapy interruption in participants completing multiple dose schedules.
5. To determine the recommended Phase 2 dosing regimen

Conditions and MedDRA coding

Chronic HIV infection

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 18-65 years
2. HLA-A*02:01-positive
3. ≥ 50 kg
4. • Evidence of HIV-1 infection • On continuous ART for a minimum of 12 months and maximum of 15 years • Consistently undetectable plasma HIV RNA (< 50 copies/mL) throughout the 12-month period prior to screening • Current CD4+ T cell count > 450 cells/μL and CD4+ cells >15% total lymphocytes • CD4+ T cell nadir > 200 cells/μL
5. Contraception
6. Informed Consent

Exclusion criteria 13

1. Confirmed HIV controller with HIV RNA consistently below 2000 copies/mL for at least 12 months and on ≥ 2 determinations.
2. Initiated ART within 12 weeks of a diagnosis of primary HIV infection (PHI) Diagnosis of PHI is confirmed by any of: a. positive HIV-1 serology preceded by a recent negative HIV-1 antibody (Ab) test, b. Negative HIV Ab test plus positive viral antigen or RNA test c. HIV-1 Ab avidity test consistent with recent infection, or d. Weakly reactive or equivocal 4th generation HIV Ab/Ag test.
3. Recent diagnosis of an AIDS-defining condition within 90 days prior to screening excludes participation in Part 1. Any history of AIDS-defining condition excludes participation in Part 2.
4. Individuals receiving an ART regimen containing a non-nucleoside reverse transcriptase inhibitor may not enrol in Part 2 unless willing and able to switch to a short-acting alternative prior to receiving their first dose of study drug.
5. Medical Conditions Co-infection with HBV Current active Mycobacterium tuberculosis infection or known untreated latent infection. Significant cardiovascular disease or impaired cardiac function Active autoimmune disease requiring immunosuppressive treatment Prior solid organ or bone marrow transplant. History of malignant disease Pregnant or lactating women.
6. Recent immunotherapy medication Systemic treatment with steroids or any other immunosuppressive drug use
7. Prior treatment with investigational HIV-targeted therapy
8. Recent use of live vaccine
9. Prior treatment with ImmTAC molecule
10. Participation in other interventional studies
11. If any of the following 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 not clinically significant by the physician Investigator, the participant may be considered for enrolment: a. Hemoglobin < 120 g/L for participants assigned male at birth; < 110 g/L for participants assigned female at birth b. Platelet count < 150 × 109/L c. Alanine aminotransferase (ALT) > 3 × ULN (upper limit of normal) d. eGFR(Foundation, 2009) < 60 mL/min/1.73 m2 (calculated using CKD-EPI equation, 2009; or measured)
12. Inability or unwillingness to adhere to safer sex practices during ART interruption.
13. Hypersensitivity to study treatment or excipient Any medical condition that would interfere with the participation in the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • 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) and AEs leading to treatment interruption, dose reduction, or discontinuation through 28 days after the last infusion of study treatment

Secondary endpoints 3

1. IMC-M113V pharmacokinetics (PK) parameters (eg, AUC, Cmax, Tmax, t1/2) at multiple time points from baseline up to 72 hours post-dose in SAD and MAD (first dose) and after each subsequent dose in MAD studies Incidence of anti-IMC-M113V antibody formation following administration of one or more doses of study drug
2. Change in serum cytokines/chemokines and peripheral blood lymphocyte counts (absolute values and fold-change) from baseline through 72 hours post-dosing with IMC-M113V in SAD and MAD schedules and during Follow-Up.
3. • Proportion of participants with pVL < 200 copies/mL 12 weeks after interruption of ART (W24) • Proportion of participants resuming ART before W24 • Duration of post-treatment control (pVL < 200 copies/mL) after interruption of ART • Duration of virological suppression (pVL <1000 copies/mL) after interruption of ART Identification of at least 1 tolerable dosing regimen for further evaluation in subsequent development

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Immunocore Limited

Sponsor organisation

Immunocore Limited

Address

92 Park Drive, Milton Milton

City

Abingdon

Postcode

OX14 4RY

Country

United Kingdom

Scientific contact point

Organisation

Immunocore Limited

Contact name

Regulatory Affairs

Public contact point

Organisation

Immunocore Limited

Contact name

Information desk

Third parties 4

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 46 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications