Human Immunodeficiency Virus (HIV) Infection MedDRA version: 14.1 Level: LLT Classification code 10020172 Term: HIV infection NOS System Organ Class: 10021881 - Infections and infestations MedDRA version: 14.1 Level: LLT Classification code 10020192 Term: HIV-1 System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: panobinostat
Product Code: LBH589
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PANOBINOSTAT
CAS Number: 404950-80-7
Concentration unit: mg milligram(s)
Concentration type: equ
Sponsors
Aarhus University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Documented HIV-1 infection • Age >18 years • HIV-1 plasma RNA 500/mm3 on minimum 2 occasions in the last 12 months prior to study entry • Able to give informed consent 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 16 F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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;Secondary Objective: • 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 ;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;Timepoint(s) of evaluation of this end point: Unspliced HIV-RNA to be evaluated repeatedly during study treatment (week 4-12) | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 ;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 | — |
Countries
Denmark
Contacts
Public ContactDepartment of Infectious Diseases
Aarhus University Hospital
Outcome results
None listed