HIV infection MedDRA version: 19.0 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Vacc-4x
Product Code: Vacc-4x
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Vacc-10
Current
Sponsors
Bionor Pharma ASA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects. 2. Age =18 to = 55 years. 3. All subjects must have a serologically documented HIV diagnosis. 4. Subjects receiving ART according to the national and/or International guidelines and recommendations observed by the trial centers. 5. ART maintained without interruption for at least 3 years prior to randomization. 6. Plasma HIV RNA maintained =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects with contraindications (hypersensitivity included) to Leukine®, see Appendix 1. 2. Subjects with contraindications to the practice of i.d. injections. 3. Subjects who have received a HIV experimental therapeutic or preventive vaccination or immune-modulatory or interleukin-based treatment within 3 years of randomization. 4. Subjects with a history of treatment with chemotherapeutic agents within 2 years of ran-domization. 5. Subjects on a Protease Inhibitor-based regimen during three months preceding randomization. 6. History of any latency activating agent, notably HDACi use within 24 months preceding randomization. 7. Any vaccinations within 4 weeks of randomization, excluding influenza vaccinations. 8. Any acute and clinically significant infection within the last 4 weeks of randomization. 9. Subjects with a history of AIDS defining condition. 10. Clinical abnormalities, as determined by physical examination alone, indicative of chronic active disease states. Subjects with acute or chronic conditions which are either non-stabilized or not in remission as per the investigator's opinion. 11. Subjects with a history of clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncope episodes, or additional risk factors for Torsades de Pointes (e.g. heart failure, congenital long QT syndrome). 12. Subjects receiving concomitant medication according to Appendix 5. 13. Subjects with a history of current or past: a. HBV infection. b. HBV/HDV infection. c. HCV infection. 14. Subjects with recurrent Herpes Zoster. 15. Subjects with recurrent herpes infection (HSV-1 or HSV-2 reactivation) that cannot be controlled with valaciclovir. 16. Subjects with clinically significant laboratory abnormalities: a. Hemoglobin =12 g/dL b. Platelet count =150 x109/L c. Absolute neutrophil count =2.0x109/L d. Hepatic transaminases (AST or ALT) =1.5 x ULN e. Serum total bilirubin =1.5 x ULN f. Specific or standard (CRP and CBC) =1.5 x ULN g. eGFR =60 mL/min (based on serum creatinine or other appropriate validated markers) h. Serum potassium, magnesium, phosphorus outside =1.5 x ULN/LLN 17. Subjects with acute or chronic major psychiatric conditions (i.e. schizophrenia, major depression or bipolar disease) which are either non-stabilized or not in remission as per the investigator's clinical assessment, or are in need of continual psycho-active medications. 18. Subjects with a history of multiple sclerosis including subjects in remission. 19. Subjects with a history of substance and/or alcohol abuse/dependency within the last 24 months prior to randomization. 20. Males who are unwilling to use barrier contraception during the entire course of the present trial. 21. ECG at screening that shows QTc >450 msec for males and >470 msec for women when calculated using the Fridericia formula from either lead V3 or V4. 22. Subjects who have switched ART regimens more than once due to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the immune-mediated effect on plasma VL (HIV-1 RNA) of the HIV therapeutic vaccine Vacc-4x with GM-CSF adjuvant when administered prior to HIV latent reservoir activation by the HDACi romidepsin in HIV patients on ART.; Secondary Objective: To assess the safety and tolerability of Vacc-4x when administered prior to the HDACi romidepsin in HIV patients on ART. To explore the effect of Vacc-4x on HIV viral reservoir size in CD4 T cells when ad-ministered prior to the HDACi romidepsin in HIV patients on ART. To explore virus production induced by romidepsin To assess the potential additive antiviral effect of two additional booster injections of Vacc-4x when administered prior to the HDACi romidepsin in HIV patients on ART. To explore the effects of Vacc-4x on immune responses to HIV when Vacc-4x is admin-istered prior to the HDACi romidepsin in HIV patients on ART. To explore the effects of Vacc-4x on selected markers of inflammation when adminis-tered prior to the HDACi romidepsin in HIV patients on ART. ;Primary end point(s): Plasma HIV RNA levels below 20 copies/mL 72 h after each of the three romidepsin infusions.;Timepoint(s) of evaluation of this end point: End of trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Virological Endpoints - Change from baseline in CA US HIV RNA at visits 6, 9, 12-25. - Change from baseline in proviral DNA at visits 6, 9, 12, 13, 24 and 25. - Change from baseline in plasma HIV-1 RNA (single-copy assay) at 2 h, 24 h and 72 h after each of the three romidepsin infusions. Immunological and Inflammatory Endpoints - Change from baseline in CD4 and CD8 counts at visits 13, 24 and 25. - Change from baseline in CD4/CD8 ratio at visits 13, 24 and 25. - Change from baseline in T cell proliferation to visits 6, 9, 12, 13, 21, 22, and 23. - Change from baseline in intracellular cytokines to visits 6, 9, 12, 13, 21, 22, and 23. - Change from baseline in hs-CRP to visits 13 and 25. - Change from baseline in IP-10 to visits 13 and 25. - Change from baseline in D-dimer to visits 13 and 25 - Change from baseline in sTNF1 and sTNF2 to visits 13 and 25. Pharmacodynamic Endpoint - Histone H3 acetylation to visits 13-21 and 24. Safety Endpoints - Number of AEs - Number of ARs - Number of SAEs - Number of SARs - Number of SUSARs - Laboratory safety parameters. - Plasma concentrations of romidepsin prior to romidepsin administration, close to the end of the infusion (3:45-4:00 h after infusion start) and at visits 14, 15, 17, 18, 20 and 21. Serological Endpoint - Change from baseline in Anti-Vacc C5 Ab levels to visit 13 and visit 25 (or EOT). ;Timepoint(s) of evaluation of this end point: End of trial | — |
Countries
Australia, Denmark, European Union, United States
Contacts
Public ContactJoris Wilms
Klifo A/S
Outcome results
None listed