E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV infection |
HIV-infeksjon |
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E.1.1.1 | Medical condition in easily understood language |
HIV infection |
HIV-infeksjon |
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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 | PT |
E.1.2 | Classification code | 10020161 |
E.1.2 | Term | HIV infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 compare the effects of a TLR9 agonist (Lefitolimod) and/or administration of potent bNAbs (3BNC117 and 10-1074) on time to viral rebound during analytical treatment interruption. |
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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 compare viral load (plasma HIV-1 RNA) kinetics (e.g. doubling time) between study arms - To evaluate the effect of the IMPs on the amount of 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 HIV-specific immunity, T cell phenotype, immune activation and cytokine production between study arms |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Documented HIV-1 infection - Adults age 18-65 year - On antiretroviral therapy for a minimum of 18 months - CD4+ count >500 at screening - HIV-1 RNA plasma level of < 50 copies/mL by standard assays for at least 15 months (a single viral load measurement > 50 but < 500 copies/mL during this time period is allowable) - Viral reservoir sensitivity to 3BNC117 and 10-1074 (analyzed using the PhenoSense HIV mAb Assay, Monogram Biosciences). - Able to give informed consent |
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E.4 | Principal exclusion criteria |
- Any significant acute medical illness requiring hospitalization in the past 4 weeks - Any evidence of an active AIDS-defining opportunistic infection - Any condition that, in the Investigator's opinion, will prevent adequate compliance with study therapy - The following laboratory values at screening, the values can be repeated within the screening period, but test results must be available before baseline (Day 0) and checked for eligibility: o Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN) o Serum total bilirubin ≥3 ULN o Estimated glomerular filtration rate (eGFR) ≤50 mL/min (based on serum creatinine) o Platelet count ≤100 x109/L o Absolute neutrophil count ≤1x109/L - Hepatitis B or C infection as indicated by the presence of hepatitis B surface antigen or hepatitis C virus RNA in blood - History of: o Malignancy, excluding non-melanoma skin cancers, or organ transplantation - Receipt of strong immunosuppressive or systemic chemotherapeutic agents within 28 days prior to study entry - Known resistance to >2 classes of ART - Known hypersensitivity to the components of lefitolimod, 3BNC117, 10- 1074 or their analogues - Pre-existing autoimmune or antibody-mediated diseases - Women who are pregnant or breastfeeding, or with a positive pregnancy test as determined by a positive urine beta- human chorionic gonadotropin test during screening or women of child bearing potential who are unwilling or unable to use an acceptable method of nonestrogen containing contraception (according to the Danish Medicines Agency guidelines) to avoid pregnancy during the study - Males or females who are unwilling or unable to use barrier contraception during sexual intercourse until plasma HIV-1 RNA is undetectable using standard assays |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time from the day of cART cessation to the day of the last of three consecutive plasma HIV-1 RNA measurements >10,000 copies/mL. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The following visits: 5-9 and 10a-10j |
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E.5.2 | Secondary end point(s) |
1. Safety evaluation, as measured by Adverse Events (AE), Adverse Reactions (ARs), Serious Adverse Events (SAE), Serious Adverse Reactions (SAR) and CD4 cell change from baseline to end of study 2. ď‚·Rebound virus kinetics including time to >50 copies/mL and >1,000 copies/mL as well as doubling time during the analytical treatment interruption as measured by plasma HIV-1 RNA (Cobas TaqMan; Lower limit of quantitation 20 copies/mL) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. All visits 2. During the analytical treatment interruption (visit 5-9 and 10a-10j) |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
|
Last visit of the last subject |
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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 | 0 |
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 | 0 |