Safety and Efficacy of Romidepsin and the Therapeutic Vaccine Vacc-4x for Reduction of the Latent HIV-1 Reservoir (REDUC)

Bionor Immuno

Status and phase: Completed; Phase 2; Phase 1

Conditions: HIV I Infection

Treatments: Biological: Vacc-4x; Biological: rhuGM-CSF; Drug: Romidepsin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02092116

2013-004747-23 (EudraCT Number)

BPC01-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

Part A

Other group

Description:

Pre-treatment phase of 2-4 weeks (Visit 1- Visit 2a) followed by viral reactivation phase of 3 weeks (Visit 2 to Visit 7) consisting of one cycle of romidepsin infusions at a dosing of 5 mg/m2 on days 0, 7, and 14. Post-activation phase of \~9 weeks (Visit 8 to Visit 11) to assess the effect of romidepsin on the size of latent HIV-1 reservoir.

Treatment:

Drug: Romidepsin

Part B

Other group

Description:

Pre-treatment phase of 2-4 weeks (Visit 1-Visit 2) followed by a therapeutic HIV-1 immunization phase of 12 weeks (Visit 2 to Visit 7) in which 1.2 mg Vacc-4x was administered together with 0.06 mg rhuGM-CSF at Visits 2, 3, 4, 5, 6 and 7 follow by a follow-up period of 2 weeks (Visit 8). A viral reactivation phase of 3 weeks (Visit 9-Visit 11) consisting of one cycle of 3 romidepsin infusions (5 mg/m2) followed by a post-treatment observation phase of \~9 weeks (Visit 12-Visit 13) to assess the effect of the investigational treatment on the size of the latent HIV-1 reservoir. A monitored antiretroviral pause of up to 16 weeks (Visit 14-Visit 33).

Treatment:

Drug: Romidepsin

Biological: rhuGM-CSF

Biological: Vacc-4x