Research In Viral Eradication of HIV Reservoirs

NCT02336074 | Completed Phase 2 Results DMC

• 2 other identifiers: CCT-NAPN-247722014-001425-32
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 6

Brief Summary

This study will be a two-arm prospective 1:1 randomised controlled trial comparing: Arm A: cART preferably including raltegravir (combination ART cART - control) Arm B: cART preferably including raltegravir (cART) plus ChAdV63.HIVconsv (ChAd) prime and MVA.HIVconsv (MVA) boost vaccines; followed by a 28-day course of vorinostat (10 doses in total). We hypothesise that this intervention in primary HIV infection will confer a significant reduction in the latent HIV reservoir when compared with cART alone. .

Conditions

HIV

Keywords

HIV; Vaccine; Cure; Early Intervention; Infection; Primary infection; Reservoir; Vorinostat; HDAC

Outcome Measures

Primary Outcomes (1)

• Total HIV DNA From CD4 T-cells

  The average of two measures taken at post-randomisation week 16 and 18

  Averaged across post-randomisation week 16 and 18

Secondary Outcomes (5)

• Clinical Adverse Events

  From randomization to the final visit at week 18.

• Quantitative Viral Outgrowth

  At week 16

• Percentage of CD4+ CD154+ IFNγ+ T Cells

  12 weeks

• CD8+ T-cell Responses

  12 weeks

• Viral Inhibition

  12 weeks

Study Arms (2)

Control

ACTIVE COMPARATOR

Combination Antiretroviral Therapy (cART) preferably including raltegravir prescribed at week 0 for the duration of the study up to post-randomisation week 18 (42 weeks in total)

Drug: Combination Antiretroviral Therapy (cART); Drug: Raltegravir

Intervention

EXPERIMENTAL

Combination Antiretroviral Therapy (cART) preferably including raltegravir prescribed at week 0 for the duration of the study up to post-randomisation week 18 (42 weeks in total) Plus ChAdV63.HIVconsv prime (post-randomisation week 00) and MVA.HIVconsv boost (post randomisation week 08 day 1) vaccines; followed by a 28-day course of vorinostat (10 doses in total).

Drug: Combination Antiretroviral Therapy (cART); Drug: Raltegravir; Drug: Vorinostat; Biological: ChAdV63.HIVconsv (ChAd); Biological: MVA.HIVconsv (MVA)

Interventions

Combination Antiretroviral Therapy (cART) DRUG

Likely consisting of an Nucleoside reverse-transcriptase inhibitor (NRTI) backbone i.e. Truvada plus a ritonavir-boosted protease inhibitor (PI) e.g. Darunavir + ritonavir. Prescribed at week 0 for the duration of the study.

Control; Intervention

Raltegravir DRUG

All participants will be dispensed sufficient supplies of Raltegravir to ensure they have sufficient medication to last to the next study visit. Raltegravir is supplied in marketed pack with 30 tablets per bottle.

Also known as: Isentress

Control; Intervention

Vorinostat DRUG

Vorinostat (suberoylanilide hydroxamic acid abbreviated to SAHA) inhibits the histone deacetylases HDAC1, HDAC2, HDAC3 (Class I) and HDAC6 (Class II). Vorinostat is supplied as capsules containing 100mg vorinostat and the following inactive ingredients: microcrystalline cellulose, sodium croscarmellose and magnesium stearate.

Intervention

ChAdV63.HIVconsv (ChAd) BIOLOGICAL

Dosage: 5x1010vp .This dose is obtained by injecting 0.37ml of the vaccine at 1.35x1011vp/ml without dilution. This prime vaccination is administered intramuscularly (IM) into the deltoid muscle of the non-dominant arm at post-randomisation week 00.

Intervention

MVA.HIVconsv (MVA) BIOLOGICAL

Dosage: 2x108pfu Administration: This dose is obtained by injecting 0.23 ml of the vaccine IM at 8.6x108pfu/ml without dilution. This boost vaccination is administered intramuscularly (IM) into the deltoid muscle of the non-dominant arm at post-randomisation week 08 Day 1 (2 prior to start of vorinostat)

Intervention

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged ≥18 to ≤60 years old
• Able to give informed written consent including consent to long-term follow-up
• Should be enrolled within a maximum of 4 weeks of a diagnosis of primary HIV-1 infection confirmed by one of the following criteria:
• Positive HIV-1 serology within a maximum of 12 weeks of a documented negative HIV-1 serology test result (can include point of care test (POCT) using blood for both tests)
• A positive p24 antigen result and a negative HIV antibody test
• Negative antibody test with either detectable HIV RNA or proviral DNA
• PHE RITA test algorithm (a) reported as "Incident" confirming the HIV-1 antibody avidity is consistent with recent infection (within the preceding 16 weeks).
• Weakly reactive or equivocal 4th generation HIV antibody antigen test
• Equivocal or reactive antibody test with \<4 bands on western blot
• Adequate haemoglobin (Hb≥12g/dL for males, ≥11g/dL for females)
• Weight ≥50kg
• Willing to be treated with cART (preferably including raltegravir) and be randomised to continue cART alone or cART plus intervention (HIV vaccines plus HDACi)
• Willing and able to comply with visit schedule and provide blood sampling

You may not qualify if:

• Women of child bearing potential (WCBP) (b)
• In women with intact ovaries and no uterus, any planned egg donation anytime in the future to a surrogate
• Intention to donate sperm or father a child within 6 months of the intervention
• Co-infection with hepatitis B (surface antigen positive or detectable HBV DNA levels in blood) or hepatitis C (HCV RNA positive or HVC antigen positive)
• Any current or past history of malignancy
• Concurrent opportunistic infection or other comorbidity or comorbidity likely to occur during the trial e.g.past history of ischaemic or other significant heart disease, malabsorption syndromes, autoimmune disease
• Any contraindication to receipt of BHIVA recommended combination antiretrovirals
• HIV-2 infection
• Known HTLV-1 co-infection
• Prior immunisation with any experimental HIV Immunogens (including any component of the vaccines used in the RIVER protocol; simian or human adenoviral vaccine; other experimental HIV vaccines)
• Current or planned systemic immunosuppressive therapy (inhaled corticosteroids are allowed)
• Any history of proven thromboembolism (pulmonary embolism or deep vein thrombosis)
• Any inherited or acquired bleeding diathesis including gastric or duodenal ulcers, varices
• Concurrent or planned use of any drugs contraindicated with vorinostat i.e. antiarrhythmics; any other drugs that prolong QTc; warfarin, aspirin, sodium valproate
• Prior intolerance of any of either the components of the vaccine or HDACi,

Sponsors & Collaborators

• Imperial College London: lead
• Medical Research Council: collaborator
• University of Oxford: collaborator
• University of Cambridge: collaborator
• Chelsea and Westminster NHS Foundation Trust: collaborator
• Royal Free Hospital NHS Foundation Trust: collaborator
• Brighton and Sussex University Hospitals NHS Trust: collaborator
• Guy's and St Thomas' NHS Foundation Trust: collaborator
• Central and North West London NHS Foundation Trust: collaborator

Study Sites (6)

Brighton and Sussex University Hospitals NHS Trust

Brighton, United Kingdom

Location

Central and North West London NHS Foundation Trust

London, United Kingdom

Location

Chelsea and Westminster NHS Foundation Trust

London, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, United Kingdom

Location

Royal Free Hospital NHS Foundation Trust

London, United Kingdom

Location

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Related Links

• CHERUB (Collaborative HIV Eradication of viral Reservoirs: UK BRC) website
• Medical Research Council Clinical Trials Unit

MeSH Terms

Conditions

Infections

Interventions

Antiretroviral Therapy, Highly Active; Raltegravir Potassium; Vorinostat

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Professor Sarah Fidler
• Organization: Imperial College London

s.fidler@imperial.ac.uk

004420331

Study Officials

• Sarah Fidler, MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2014
• First Posted: January 12, 2015
• Study Start: November 27, 2015
• Primary Completion: November 15, 2017
• Study Completion: March 31, 2023
• Last Updated: October 23, 2023
• Results First Posted: September 25, 2019

Record last verified: 2023-10

Locations

GB (6)