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

Phase 1

Conditions: Chronic HIV infection
MedDRA version: 20.1Level: PTClassification code 10020161Term: HIV infectionSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2021-002008-11-BE

Lead Sponsor: Immunocore Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 53

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 < 50 copies/mL at Screening and at all available determinations in the 12-month period preceding Screening
7. Current CD4+ T cell count > 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

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 < 2000 copies/mL in absence of ART for at least 12 months and on = 2 determinations.
2. Initiated ART within 12 weeks of a diagnosis of primary HIV infection, confirmed by any of the following:
a. Positive HIV-1 serology = 12 weeks after a documented negative HIV-1 antibody (Ab) test,
b. Negative HIV Ab test plus either positive p24 antigen (Ag) test or detectable HIV RNA,
c. HIV-1 Ab avidity test consistent with recent infection, or
d. Weakly reactive or equivocal 4th generation HIV Ab/Ag test.
3. Prior AIDS-defining condition will preclude participation in Part 1 if diagnosed within 90 days prior to Screening. A prior AIDS-defining condition at any time will preclude 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.
Medical Conditions
5. Co-infection with HBV (defined as positive HBsAg test or detectable HBV DNA) or HCV infection (defined as detectable HCV RNA).
6. Current active Mycobacterium tuberculosis infection or known untreated latent infection.
7. History of clinically significant cardiovascular disease or impaired cardiac function, including any of the following:
a. Congestive heart failure (New York Heart Association Class =3).
b. Uncontrolled hypertension (consistent findings of systolic blood pressure [BP] >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. Pregnant or lactating women.
12. Use of blood products, cytokine therapy or other immunotherapy or immunosuppressive medication in the preceding 3 months from Screening.
13. 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
14. History of any investigational HIV immunotherapy or vaccine within 6 months of Screening.
15. Planned receipt of vaccines: live vaccines are not permitted within 28 days, and non-live vaccines