BISPECIFIC PROTEIN WITH A HIGH-AFFINITY T-CELL RECEPTOR DOMAIN FUSED TO AN ANTIBODY SINGLE-CHAIN VARIABLE FRAGMENT AGAINST CD3 for Chronic HIV infection|HIV infection

Inclusion criteria

• {"criterion_text":"- 18-65 years\n- HLA-A*02:01-positive\n- ≥ 50 kg\n- •\tEvidence of HIV-1 infection •\tOn continuous ART for a minimum of 12 months and maximum of 15 years •\tConsistently undetectable plasma HIV RNA (< 50 copies/mL) throughout the 12-month period prior to screening •\tCurrent CD4+ T cell count > 450 cells/μL and CD4+ cells >15% total lymphocytes •\tCD4+ T cell nadir > 200 cells/μL\n- Contraception\n- Informed Consent"}

Exclusion criteria

• {"criterion_text":"- Confirmed HIV controller with HIV RNA consistently below 2000 copies/mL for at least 12 months and on ≥ 2 determinations.\n- Participation in other interventional studies\n- 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)\n- Inability or unwillingness to adhere to safer sex practices during ART interruption.\n- Hypersensitivity to study treatment or excipient Any medical condition that would interfere with the participation in the study\n- 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.\n- 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.\n- 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.\n- 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.\n- Recent immunotherapy medication Systemic treatment with steroids or any other immunosuppressive drug use\n- Prior treatment with investigational HIV-targeted therapy\n- Recent use of live vaccine\n- Prior treatment with ImmTAC molecule"}

Primary endpoints

• {"endpoint_text":"- \tIncidence and severity of treatment-emergent adverse events (TEAEs)\n- \tIncidence of dose-limiting toxicities (DLTs)\n- \tChanges in safety laboratory parameters, vital signs, and electrocardiogram (QTcF)\n- \tIncidence 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","definition_or_measurement_approach":"Endpoints are safety-focused and assessed during treatment and up to 28 days after the last infusion; measurements include recorded TEAEs and SAEs, identification of DLTs, laboratory safety parameters, vital signs, and ECG QTcF monitoring as recorded in study visits and safety assessments."}

Secondary endpoints

• {"endpoint_text":"- 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\n- Incidence of anti-IMC-M113V antibody formation following administration of one or more doses of study drug","definition_or_measurement_approach":"PK parameters (AUC, Cmax, Tmax, t1/2) measured at specified time points from baseline up to 72 hours post-dose in SAD and MAD; anti-drug antibody incidence measured following dosing."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Serum cytokines/chemokines and peripheral blood lymphocyte counts assessed as absolute values and fold-change from baseline through 72 hours post-dose and during follow-up."}
• {"endpoint_text":"- \tProportion of participants with pVL < 200 copies/mL 12 weeks after interruption of ART (W24)\n- \tProportion of participants resuming ART before W24\n- \tDuration of post-treatment control (pVL < 200 copies/mL) after interruption of ART\n- \tDuration of virological suppression (pVL <1000 copies/mL) after interruption of ART\n- Identification of at least 1 tolerable dosing regimen for further evaluation in subsequent development","definition_or_measurement_approach":"Virological endpoints assessed after analytical treatment interruption (ATI), with pVL thresholds (<200 and <1000 copies/mL) measured at scheduled visits (including W24) to determine proportions, durations of post-treatment control, and ART resumption; identification of tolerable dosing regimen based on safety and PD outcomes."}

Methods

• Use of recruitment materials and public-facing content: Banner Ads (K2_Banner Ads_EN; K2_Recruitment material_Banner Advertisements), Social Media Clinical Trial Posts (K2_Social Media_Clinical Trial Posts), Patient Posters and Brochures (K2_Patient Poster, K2_Patient Brochure Part 2), and ePR content (K2_ePR Content) targeted to potential participant populations (people with chronic HIV infection on ART and HLA-A*02:01-positive).
• Country-specific materials: Belgium-targeted materials available in NL, FR and EN (e.g. versions labelled for BE: NL/FR/EN); Spain-targeted materials available in Spanish (e.g. K2_Recruitment material_Patient Brochure Part 2_red, K2_Recruitment material_Banner Advertisements V01ESP01).

Belgium

Earliest CTIS Part Ii Submission Date

23-07-2024

Latest Decision Or Authorization Date

08-01-2025

Processing Time Days

169

Number Of Sites

2

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

23-07-2024

Latest Decision Or Authorization Date

05-05-2026

Processing Time Days

651

Number Of Sites

4

Number Of Participants

10

Primary sponsor

Full Name

Immunocore Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Iqvia Biotech Limited

Responsibilities

sponsorDuties codes: 1, 12, 2, 6, 8

Name

Medidata Solutions International Limited

Responsibilities

sponsorDuties codes: 3, 6, 7

Third parties

• {"country":"United States","full_name":"American Red Cross (ARC)","duties_or_roles":"HLA subtyping for patient selection","organisation_type":"Health care"}
• {"country":"United States","full_name":"Q Squared Solutions Holdings LLC","duties_or_roles":"CTL PBMC Processing, IL-6 (Part#1373), Interferon-gamma (IP-10), Serum (Part#1846), 5 Plex MSD, Serum (sponsorDuties entries)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"sponsorDuties codes: 1, 12, 2, 6, 8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Medidata Solutions International Limited","duties_or_roles":"sponsorDuties codes: 3, 6, 7","organisation_type":"Pharmaceutical company"}