Clinical trial NCT02092116: Safety and Efficacy of Romidepsin and the Therapeutic Vaccine Vacc-4x for Reduction of the Latent HIV-1 Reservoir
Official title: An Open Phase I/IIa Study to Evaluate the Safety and Effect of Therapeutic HIV-1 Immunization Using Vacc-4x + rhuGM-CSF and HIV-1 Reactivation Using Romidepsin on the Viral Reservoir in Virologically Suppressed HIV-1 Infected Adults on cART
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV I Infection
Lead sponsor: Bionor Immuno AS
Sponsor class: INDUSTRY
Collaborators: name: Celgene Corporation
First posted: 2014-03-19
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The REDUC trial's objective is to address one of the core issues with the treatment of HIV, which is that some HIV infected cells hide in so-called latent reservoirs. The reservoirs are unaffected by conventional HIV medication and invisible to the immune system. HDACi have the potential to activate these latently infected cells. This will make the HIV infected cells visible to the immune system; the immune response generate by Vacc-4x will be able to attack and eliminate the infected cells.

Detailed description: The study is divide into two parts. In Part A the safety and tolerability of romidepsin will be evaluated and the effect of romidepsin treatment on HIV-1 transcription in HIV-infected patients virologically suppressed on cART will be determined.

In Part B the effect of treatment with Vacc-4x + rhuGM-CSF and romidepsin treatment on the HIV-1 latent reservoir in HIV-infected patients virologically suppressed on cART will be measured.

Six patients will be enrolled for part A and the safety and tolerability profile evaluated before enrolling 20 patients in B.

Eligibility criteria: Inclusion Criteria:

1. Age \>18 years
2. Currently receiving cART and having received cART for a minimum of 1 year
3. HIV-1 plasma RNA \<50 copies/mL for at least 1 year (excluding viral load blips)
4. CD4 T cell count ≥500 cells/mm3

Exclusion Criteria:

1. CD4 T cell count nadir \<200 cells/mm3
2. Previous treatment with an HDACi (Histone deacetylase inhibitor) within the previous 6 months
3. Any evidence of an active AIDS-defining opportunistic infection, active HBV or HCV co-infection, significant cardiac disease, malignancy, transplantation, insulin dependent diabetes mellitus or other protocol defined excluded medical condition
4. Use of any protocol defined contraindicated medication or vaccination
5. Unacceptable values of the hematologic and clinical chemistry parameters as defined in the protocol.
6. Males or females who are unwilling or unable to use protocol defined methods of contraception

Primary outcomes:
measure: Part A: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: 3 weeks
measure: Part B: Changes From Baseline in HIV-1 Reservoir (Total HIV-1DNA; Integrated HIV-1 DNA in Unfractionated CD4+ T Cells and Replication Competent Provirus.
timeFrame: Day 161/175
Secondary outcomes:
measure: Part A: Changes From Baseline in HIV-1 Reservoir (Total HIV-1DNA; Integrated HIV-1 DNA in Unfractionated CD4+ T Cells and Replication Competent Provirus. Estimates of Change From Baseline of the Size of the Latent HIV-1 Reservoir in CD4+ Cells.
timeFrame: Day 56/84
measure: Part B: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: 287 days
measure: Part B: Level of HIV-1 Transcription.
timeFrame: Day 105, 112 and 119
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital, Skejby Sygehus
Study officials:
affiliation: Aarhus University Hospital
name: Lars Jørgen Østergaard, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leth S, Schleimann MH, Nissen SK, Hojen JF, Olesen R, Graversen ME, Jorgensen S, Kjaer AS, Denton PW, Mork A, Sommerfelt MA, Krogsgaard K, Ostergaard L, Rasmussen TA, Tolstrup M, Sogaard OS. Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial. Lancet HIV. 2016 Oct;3(10):e463-72. doi: 10.1016/S2352-3018(16)30055-8. Epub 2016 Jul 7.
citation: Sogaard OS, Graversen ME, Leth S, Olesen R, Brinkmann CR, Nissen SK, Kjaer AS, Schleimann MH, Denton PW, Hey-Cunningham WJ, Koelsch KK, Pantaleo G, Krogsgaard K, Sommerfelt M, Fromentin R, Chomont N, Rasmussen TA, Ostergaard L, Tolstrup M. The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo. PLoS Pathog. 2015 Sep 17;11(9):e1005142. doi: 10.1371/journal.ppat.1005142. eCollection 2015 Sep.