E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV infection |
HIV infektion |
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E.1.1.1 | Medical condition in easily understood language |
HIV infection |
HIV infektion |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020180 |
E.1.2 | Term | HIV positive |
E.1.2 | System Organ Class | 100000004848 |
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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 |
Evaluate the effects of romidepsin plus 3BNC117 or romidepsin alone on delaying or preventing viral rebound in HIV-1-infected individuals during an analytical interruption of ART. |
Vurdere effekten af romidepsin plus 3BNC117 eller romidepsin alene på tiden til genopblussen af virus hos HIV-1 patienter under en monitoreret behandlingspause af HIV behandlingen. |
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E.2.2 | Secondary objectives of the trial |
1) Evaluate the safety of romidepsin plus 3BNC117 or romidepsin alone in ART-treated HIV-1 infected individuals 2) Evaluate the effects of romidepsin plus 3BNC117 or romidepsin alone on the size of the replication competent HIV-1 reservoir in ART-treated HIV-1-infected individuals; 3) Evaluate the immunomodulatory effects of romidepsin plus 3BNC117 or romidepsin alone in ART-treated HIV-1-infected individuals.
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1) Vurdere sikkerheden af romidepsin plus 3BNC117 eller romidepsin alene hos HIV-1 patienter, som er i HIV-behandling 2) Vurdere effekten af romidepsin plus 3BNC117 eller romidepsin alene på størrelsen af det replikationskompetente reservoir hos HIV-1 patienter, som er i HIV-behandling 3) Vurdere de immunomodulatoriske effekter af romidepsin plus 3BNC117 eller romidepsin alene hos HIV-1 patienter, som er i HIV-behandling |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Adults age 18-65 years with documented HIV-1 infection 2) CD4+ T-cell count >500 cells/mm3 at screening 3) On ART for a minimum of 18 months and HIV-1 RNA plasma level of < 50 copies/ml by standard assays for at least 12 months (a single viral load measurement > 50 but < 500 copies/ml during this time period is allowable). 4) Individuals on protease inhibitor or NNRTI-based regimens must be willing to switch to an integrase-inhibitor-based regimen (raltegravir or dolutegravir) prior to enrollment. |
1) Alder mellem 18 og 65 år med dokumenteret HIV-1 infektion 2) CD4+ T celletal >500 celler/mm3 ved screening 3) HIV-behandlet i minimum 18 måneder med HIV-1 RNA i blodet <50 kopier/ml for minimum 12 måneder (et enkelt virus-blip >50, men <500 kopier/ml i periosden er tilladt) 4) HIV-1 patienter, som får behandlingsregimen baseret på enten proteasehæmmer eller NNRTI, skal skiftes til et integrasehæmmer-baseret (raltegravir eller dolutegravir) forud for inklusion |
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E.4 | Principal exclusion criteria |
1) Use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the investigators within the last 6 months 2) Pregnancy as determined by a positive urine beta-hCG. 3) Participant unwilling to use two reliable contraception methods (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) for the study duration. 4) Currently breast-feeding. 5) History of resistance to 2 or more classes of antiretroviral medication 6) Any medical, psychiatric, social, or occupational condition that, as judged by the investigators, would interfere with the evaluation of study objectives (such as severe alcohol or drug abuse, dementia). 7) 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. 8) Receipt of an HDAC inhibitor or 3BNC117 in the past 2 years. 9) Have a history of AIDS-defining illness within 3 years prior to enrollment. 10) History of significant coronary artery disease, myocardial infarction, percutaneous coronary intervention with placement of cardiac stents. 11) ECG at screening that shows QTc >450 msec when calculated using the Fridericia formula from either lead V3 or V4. 12) Use of Coumadin or Coumadin derivatives 13) Laboratory abnormalities in the parameters listed below: 13a) Absolute neutrophil count ≤ 1,300 13b) Hemoglobin ≤ 10 gm/dL 13c) Platelet count ≤ 125,000 13d) ALT ≥ 2.0 x ULN 13e) AST ≥ 2.0 x ULN 13f) Total bilirubin ≥ 2.0 x ULN (for participants on atazanavir, a total bilirubin up to 3 x ULN is allowable) 13g) eGFR < 60 mL/min/1.73m2 14) Any vaccination within 14 days prior to 3BNC117 administration 15) Receipt of any therapeutic HIV vaccine in the past 16) Receipt of any monoclonal antibody therapy of any kind in the past 2 years 17) Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study. |
1) Brug af immunmodulerende midler eller systemisk kemoterapi indenfor de seneste 6 måneder før inklusion 2) Gravid eller positiv graviditetstest under screening hos kvinder i den fødedygtige alder eller kvinder, der planlægger at blive gravide i forsøgsperioden, som ikke kan/vil benytte sikker antikonception (indeholde ikke-østrogener i henhold til Sundhedsstyrelsens retningslinjer) i hele studieperioden 3) Mænd eller kvinder, som ikke kan/vil bruge barriereprævention (kondom/femidom) i hele studieperioden 4) Ammende kvinde 5) Kendt resistens overfor >2 regimer af HIV behandling 6) Aktuel alkohol- eller stofmisbrug, som Investigator finder ensbetydende med manglende compliance i henhold til forsøgsplanen 7) Hepatitis B or C infektion ved tilstedeværelsen af hepatitis B overflade antigen (HBsAg) eller hepatitis C virus RNA (HCV-RNA) i blodet 8) Tidligere behandlet med: HDACi eller 3BNC117 indenfor de seneste 2 år 9) AIDS-definerende opportunistisk infektion seneste 3 år før screening 10) Medicinsk historie med: Alvorlig hjertesygdom, symptomatisk eller asymptomatisk arytmier, besvimmelsesepisoder, eller øget risiko for Torsades de pointes (ved f.eks. hjertesvigt) 11) Elektrokardiogram ved screening, som viser QTc >450 ms, når beregnet ved Fridericia formula fra enten afledning V3 eller V4 12) Brug af warfarin or warfarin-derivater 13) Laboratoriemæssig forhold ved screening: 13a) Antal neutrofile granolucytter ≤1.3 x109/L 13b) Hæmoglobin ≤ 10 gm/dL 13c) Antal blodplader ≤125 x109/L 13d+e) Leverenzymer (aspartat-aminotransferase eller alanin-aminotransferase) ≥2 x øvre normalgrænse (ULN) 13f) Total bilirubin ≥2 ULN (hvis behandles med atazanavir, da ≥3 ULN) 13g) Estimated glomerular filtration rate (eGFR) ≤60 mL/min (baseret på serum kreatinin eller anden valid markør) 14) Vaccineret indenfor 14 dage i forhold til 3BNC117 infusion 15) Tidligere behandlet med: HIV vaccine 16) Tidligere behandlet med: Monoklonale antistoffer mod HIV indenfor de seneste 2 år 17) Deltaget i andre interventionsstudier indenfor seneste 12 uger fra screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Days to viral rebound during analytic treatment interruption or days to reinitiation of ART in participants who restart ART before viral rebound. Viral rebound is defined as HIV-1 RNA ≥ 200 on 2 consecutive measurements during ATI. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During analytic treatment interruption. |
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E.5.2 | Secondary end point(s) |
1) Safety evaluation, as measured by rate and severity of adverse events (AE), serious adverse events (SAE), and serious unexpected serious adverse reactions (SUSAR) 2) Size of the functional, latent HIV-1 reservoir as determined by the number of infectious units per 106 resting memory CD4+ T cells (IUPM) using a viral outgrowth assay before and after therapy. Post therapy measurements will occur after the second cycle, just before ATI. These measurements will be performed in Dr. Siliciano’s laboratory 3) Size of the proviral HIV-1 reservoir as determined by total HIV-1 DNA and episomal HIV-1 DNA (2-LTR) in circulating total CD4+ T cells. 4) Plasma HIV-1 RNA, as measured by a routine clinical assay (Cobas Taqman; detection limit 20 copies/mL) and a transcription mediated amplification (TMA)-based assay. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) During trial 2) Before and after therapy 4) During trial |
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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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
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 |
Denmark |
Germany |
United States |
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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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LVLS. |
Sidste besøg sidste deltager |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |