E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV persistence during initiation of antiretroviral therapy |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10073675 |
E.1.2 | Term | HIV infection CDC category unspecified |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effects of IMPs (romidepsin and 3BNC117)on the size of the latent HIV reservoir in patients initiating antiretroviral treatment. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability of the Investigational Medicinal Products (IMP)s • To evaluate the effect of the IMPs on the amount of integrated HIV-1 DNA in CD4+ T cells • To evaluate the effect of the IMPs on the functional HIV-1 reservoir in CD4+ T cells • To compare viral load (plasma HIV-1 RNA) kinetics between the different study arms • To compare the levels of immune reconstitution (CD4+ T cell recovery) between the different study arms • To evaluate the effect of early viral reactivation by IMPs on the immunological control of HIV-infection following optional ART interruption • To compare HIV-specific immunity, T cell phenotype, immune activation, and cytokine production between the investigational treatment regimens
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Documented HIV-1 infection - No current or prior antiretroviral therapy - Age >18 years - CD4+ T-cell count >200/µL on last visit prior to study entry - Able to give informed consent |
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E.4 | Principal exclusion criteria |
- Current immunosuppressive therapy - Ongoing AIDS-defining condition - Pregnancy as determined by a positive urine beta-hCG (if female). - Participant unwilling to use reliable contraception methods for the duration of the trial. Reliable methods of birth control include: pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; surgical sterilization; vaginal ring; intrauterine device; abstinence; and post-menopause (if female). - Currently breast-feeding (if female). - Any medical, psychiatric, social, or occupational condition or other responsibility that, in the judgment of the Principal Investigator (PI), would interfere with the evaluation of study objectives (such as severe alcohol abuse, severe drug abuse, dementia). - Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood - Unable to follow protocol regimen
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline (day 0) to day 365 in copies of total HIV-1 DNA per 10⁶ CD4+ T cells as measured by digital droplet PCR
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) To characterize the safety and tolerability of the intervention as measured by adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR), suspected unexpected serious adverse reactions (SUSAR), and dose-limiting toxicity. 2) To compare viral load (plasma HIV RNA) decay in the different study arms as measured by Cobas Taqman 3) To compare the level of immune reconstitution (CD4+ recovery) as measured by absolute CD4+ count 1 year post the study entry 4) To characterize changes in immune effectors functions (CD8+, NK, and NKT cells) 5) To compare changes in inflammatory markers (e.g. soluble IL-6, hsCRP, d-dimer, sCD14, sCD163) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Day 0, 7, 10, 17, 21, 24, 30, 60, 90, 180, 270, 365 1) Day 0, 7, 10, 17, 21, 24, 30, 60, 90, 180, 270, 365, 400, 407, 414, 421, 428, 435, 442, 449, 456, 470, 484, 491 3) Day 0, 7, 10, 17, 21, 24, 30, 60, 90, 180, 270, 365, 400, 407, 414, 421, 428, 435, 442, 449, 456, 470, 484, 491 4) Absolute T, NK, and NKT cell counts and phenotypic properties will be characterized using standard cell marker panels (Day 0, 30, 90, 180, 270, 365, 400, 491), functional properties of CTL, NK, and NKT cells will be investigated by analysing cytokine secretion properties, and change in the capacity of CD8 T cells and NK cells to mediate inhibition of viral replication ex vivo (Day 0, 365) 5) Day 0, 7, 10, 17, 21, 24, 30, 60, 90, 180, 270, 365, 400, 491 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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The end of the trial will be the last visit of the last subject enrolled into the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |