E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus (HIV) Infection |
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E.1.1.1 | Medical condition in easily understood language |
Human Immunodeficiency Virus (HIV) Infection |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020172 |
E.1.2 | Term | HIV infection NOS |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020192 |
E.1.2 | Term | HIV-1 |
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 re-activate HIV transcription in latently infected CD4+ T-cells as measured by an increase >0.5 log10 from baseline in copies of unspliced HIV-RNA/μg total RNA in the CD4+ T-cells of HIV-infected patients on suppressive HAART |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of oral panobinostat on the size of the latent HIV-1 reservoir • To evaluate the safety and tolerability of oral panobinostat in HIV-infected patients receiving HAART • To evaluate the effect of oral panobinostat on the immunological control of HIV-infection • To characterize the immunological events induced by oral panobinostat with regard to HIV-specific immunity, T-cell phenotype, immune activation, and cytokine production • To characterize the phylogenetic relationship between episomal HIV-DNA and plasma HIV-RNA induced by oral panobinostat and how these relate to proviral HIV-DNA and the persistent low-level viremia present prior to study intervention • To describe genetic, virological, and immunological predictors of treatment response
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Documented HIV-1 infection • Age >18 years • HIV-1 plasma RNA <50 copies/ml for at least 2 years with at least 2 viral load measures per year. Episodes of a single HIV plasma RNA 50-199 copies/ml will not exclude participation if the subsequent HIV plasma RNA was <50 copies/ml • Receiving HAART, defined as at least 2 nucleoside/nucleotide reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor, integrase inhibitor, or a protease inhibitor • CD4+ T-cell count >500/mm3 on minimum 2 occasions in the last 12 months prior to study entry • Able to give informed consent
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E.4 | Principal exclusion criteria |
• Any significant acute medical illness in the past 8 weeks • Any evidence of an active AIDS-defining opportunistic infection • Current or recent gastrointestinal disease that may impact the absorption of the investigational drug • Any gastrointestinal surgery that could impact upon the absorption of the investigational drug • Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy • Patient has the following laboratory values within 3 weeks before starting the investigational drug (lab tests may be repeated, as clinically indicated, to obtain acceptable values before failure at screening is concluded but supportive therapies are not to be administered within the week prior to screening tests for ANC or platelet count) o Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN) o Serum total bilirubin ≥1.5 ULN o Serum creatinine levels ≥1.5 x ULN, or calculated creatinine clearance ≤60 ml/min o Platelet count ≤100 x109/L o Absolute neutrophil count ≤1.5x109/L o Serum potassium, magnesium, phosphorus outside normal limits o Total calcium (corrected for serum albumin) or ionized calcium ≤lower normal limits • 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 • A personal history of clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de pointes (e.g. heart failure) • History of malignancy or transplantation, including skin cancers or Kaposi sarcoma • History of diabetes mellitus • Use of a protease inhibitor • Receipt of immunomodulating agents, immunization or systemic chemotherapeutic agents within 28 days prior to study entry • Use of an agent definitely or possibly associated with effects on QT intervals within 2 weeks of screening • ECG at screening that shows QTc >450 msec when calculated using the Fridericia formula from either lead V3 or V4 • Known resistance to >2 classes of ART • Has known hypersensitivity to the components of panobinostat or its analogues • Current use of sodium valproate or other HDAC inhibitor • Women who are pregnant or breastfeeding, or with a positive pregnancy test during screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception (according to the Danish Medicines Agency guidelines) to avoid pregnancy for the entire study period and for at least 4 weeks before and 4 weeks after study treatment • Males or females who are unwilling or unable to use barrier contraception during sexual intercourse for the entire study period, including at least 4 weeks before, 4 weeks after study treatment, and when plasma HIV-RNA is detectable using standard assays
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HIV transcription in latently infected CD4+ T-cells as measured by copies of unspliced HIV-RNA/μg total RNA in the CD4+ T-cells of HIV-infected patients on suppressive HAART |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Unspliced HIV-RNA to be evaluated repeatedly during study treatment (week 4-12) |
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E.5.2 | Secondary end point(s) |
• Change from baseline to week 16 and 36 in the size of the latent HIV-reservoir, as measured by copies of proviral HIV-DNA per 10⁶ CD4+ T-cells • Change from baseline to week 16 and 36 in the frequency of cells latently infected with replication competent HIV, as measured by the HIV reactivation assay and expressed as infectious units per million (IUPM) • Safety evaluation, as measured by adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR), serious unexpected serious adverse reactions (SUSAR), and dose-limiting toxicity • Plasma HIV-RNA, as measured by the single copy assay • During the optional HAART-interruption study (if performed) o Time to viremia >1000 copies/ml during cessation of HAART o Time to meet criteria to restart HAART
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At week 16 and 36 post study enrollment as indicated
Plasma HIV-RNA (single copy assay) to be evaluated repeatedly during study treatment (week 4-12)
Viral rebound measures during HAART interruption to be measured repeatedly during optional HAART interruption |
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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 | 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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
First administration in HIV-infected humans |
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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 | No |
E.8.1.1 | Randomised | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
One-armed interventional proof-of-concept study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 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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Last visit of the last subject undergoing 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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |