Chronic HIV infection MedDRA version: 20.1 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
Immunocore Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age 1. 18-65 years inclusive, at time of informed consent HLA 2. HLA-A*02:01 positive (central laboratory testing) Weight 3. = 50 kg Condition Under Study and Prior Therapy 4. Documented evidence of HIV-1 infection 5. On continuous ART for a minimum of 12 months and maximum of 7 years at the time of planned first dose 6. Plasma HIV RNA 500 cells/µL 8. CD4+ T cell nadir > 200 cells/µL Contraception 9. Participants who engage in sexual activity which could result in pregnancy for themselves or their partner(s) must agree to use highly effective methods of contraception 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 contraception after this point should be discussed with a responsible physician. Highly effective methods of contraception are described in Section 10.4. a. Participants are not allowed to donate sperm from the time of enrolment until 3 months post-administration of study interventions or longer if required by local regulations. b. Participants must refrain from egg donation during the study. Informed Consent 10. Capable of giving signed informed consent as described in Section 10.1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Condition Under Study and Prior/Current Antiretroviral Therapy 1. Known HIV controller: pVL 160 mmHg or diastolic BP >110 mmHg, as defined in Section 8.5.2). c. History of ventricular arrhythmia currently requiring medical treatment or uncontrolled atrial fibrillation. d. QTcF > 470 msec on screening electrocardiograms (ECGs) or known history of congenital prolonged QT syndrome. e. Acute myocardial infarction or unstable angina pectoris = 6 months prior to screening. 8. Active autoimmune disease requiring immunosuppressive treatment, including inflammatory bowel disease (ulcerative colitis or Crohn’s disease), within 5 years of screening. 9. Participants with prior solid organ or bone marrow transplant. 10. History of malignant disease will preclude participation if diagnosed in the preceding 2 years from the planned first dose of IMC-M113V; in addition, history of systemic virus-associated cancer, including Kaposi’s sarcoma and lymphoma, will preclude participation in Part 2 if diagnosed at any time. Prior/Concomitant Therapy 11. Use of blood products, cytokine therapy or other immunotherapy or immunosuppressive medication in the preceding 3 months from screening. 12. Current or recent systemic steroid therapy (in the preceding 3 months from screening) or anticipated need for systemic steroids during the study with the following exceptions: a. Treatment for well-controlled and asymptomatic adrenal insufficiency is permitted, but replacement dosing is limited to prednisone = 12 mg daily or the equivalent. b. Local steroid therapies (eg, optic, ophthalmic, intra-articular, or inhaled medications) are acceptable. c. Premedication for allergy to contrast reagent. Prior/Concurrent Clinical Study Experience 13. History of any investigational HIV immunotherapy or vaccine within 6 months of screening. 14. Planned receipt of vaccines: live vaccines are not permitted within 28 days, and nonlive vaccines within 14 days of planned first ad
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: Single Ascending Dose (SAD) Study To evaluate the safety and tolerability of M113V when administered as a single dose during 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 Objective: •To characterise the pharmacokinetic (PK) profile of IMC-M113V in single dose and multiple dose schedules •To evaluate incidence of anti-IMC-M113V antibody formation following single and multiple infusions. •To determine pharmacodynamic 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 •To determine the incidence and duration of post-treatment control during analytical therapy interruption in participants completing multiple dose schedules •To determine the recommended Phase 2 dosing regimen;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) and AEs leading to treatment interruption, dose reduction, or discontinuation through 28 days after the last infusion of study treatment;Timepoint(s) of evaluation of this end point: Incidence rates will be used to summarise primary endpoints relating to the incidence of AEs. The denominators for incidence rate calculations will be the Safety Analysis Set (SAF) for participants in the respective part of the study (Part 1, Part 2, ATI) except for summaries of DLTs, which will be based on the SAD DLT evaluable set and MAD DLT evaluable set. Numerators will generally be based on TEAEs, which are defined as an AE that occurs after the first dose of investigational product and within 28 days of the last dose of investigational product. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •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. •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 •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 •Identification of at least 1 tolerable dosing regimen for further evaluation in subsequent development;Timepoint(s) of evaluation of this end point: •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 | — |
Countries
Belgium, Spain, United Kingdom
Contacts
Public ContactEric Phillips
Immunocore, Ltd.
Outcome results
None listed