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

NCT02092116 | Completed Phase 1 Results

• 2 other identifiers: BPC01-0012013-004747-23
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV I Infection

Outcome Measures

Primary Outcomes (2)

• Part A: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

  Safety and tolerability evaluation as measured by adverse events (AE) and serious adverse events (SAE).

  3 weeks

• 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.

  Total HIV-1 DNA and integrated HIV-1 DNA were analysed by MMRM analysis (copies/10\^6 CD4+ T cells). To estimate the frequency of infectious units per 10\^6 resting memory CD4+ T cells a quantitative viral outgrowth assay (qVOA) was used. Blood samples were obtained at Day 0, Day 105 and Day 161.

  Day 161/175

Secondary Outcomes (3)

• 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.

  Day 56/84

• Part B: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

  287 days

• Part B: Level of HIV-1 Transcription.

  Day 105, 112 and 119

Study Arms (2)

Part A

OTHER

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.

Drug: Romidepsin

Part B

OTHER

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).

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

Interventions

Romidepsin DRUG

Latency reversing agent

Also known as: Istodax®

Part A; Part B

Vacc-4x BIOLOGICAL

Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.

Also known as: A combination of Vacc-10, Vacc-11, Vacc-12 and Vacc-13

Part B

rhuGM-CSF BIOLOGICAL

Granulocyte macrophage colony stimulating factor as a local adjuvant

Also known as: Leukine®

Part B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• CD4 T cell count nadir \<200 cells/mm3
• Previous treatment with an HDACi (Histone deacetylase inhibitor) within the previous 6 months
• 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
• Use of any protocol defined contraindicated medication or vaccination
• Unacceptable values of the hematologic and clinical chemistry parameters as defined in the protocol.
• Males or females who are unwilling or unable to use protocol defined methods of contraception

Sponsors & Collaborators

• Bionor Immuno AS: lead
• Celgene Corporation: collaborator

Study Sites (1)

Aarhus University Hospital, Skejby Sygehus

Aarhus N, 8200, Denmark

Location

Related Publications (2)

• 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.

  PMID: 27658863 DERIVED

• 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.

  PMID: 26379282 DERIVED

MeSH Terms

Interventions

romidepsin; Vacc-4x; sargramostim

Results Point of Contact

• Title: Maja Sommerfelt
• Organization: Bionor Pharma ASA

ms@bionorpharma.com

+4723010960

Study Officials

• Lars Jørgen Østergaard, MD, PhD

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2014
• First Posted: March 19, 2014
• Study Start: March 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: December 1, 2015
• Last Updated: March 1, 2017
• Results First Posted: March 1, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)