Clinical trial NCT03041012: Early Administration of Romidepsin and 3BNC117 in Treatment-naïve HIV Patients Starting ART
Official title: Early Administration of Latency Reversing Therapy and Broadly Neutralizing Antibodies to Limit the Establishment of the HIV-1 Reservoir During Initiation of Antiretroviral Treatment - a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hiv
Keywords: HIV-1
Latency Reversal Agent
Immunotherapy
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Hvidovre University Hospital
name: Odense University Hospital
name: Aalborg University Hospital
name: Herning Hospital
name: Hammersmith Hospitals NHS Trust
name: St Mary's Hospital, London
First posted: 2017-02-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: To evaluate the effect of early viral reactivation by latency reversing agents (LRA) and/or administration of potent broadly neutralizing antibodies (bNAb) on the size of the latent HIV-1 reservoir in treatment naïve HIV-1 patients initiating antiretroviral therapy (ART)

Detailed description: The study will be conducted among ART naïve HIV-1-infected patients.

Subjects will continue ART while receiving LRA romidepsin and/or bNAb 3BNC117.

Eligibility criteria: Inclusion Criteria:

* Documented HIV-1 infection
* CD4+ T cell count \>200/µL on last visit prior to study entry
* ART naïve
* Able to give informed consent

Exclusion Criteria:

* Any significant acute medical illness (not including primary HIV infection) in the past 8 weeks
* Any evidence of an active AIDS-defining opportunistic infection
* Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy
* The following laboratory values at screening, but the values can be repeated within the screening period, but test results must be available before baseline (day 0) and checked for eligibility:

  * Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN)
  * Serum total bilirubin ≥3 ULN
  * Estimated glomerular filtration rate (eGFR) ≤60 mL/min (based on serum creatinine or other appropriate validated markers)
  * Platelet count ≤100 x10\^9/L
  * Absolute neutrophil count ≤1x10\^9/L
  * Serum potassium, magnesium, phosphorus outside ≥1.5 ULN/LLN
  * Total calcium (corrected for serum albumin) or ionized calcium ≥1.5 ULN/LLN
  * Hepatitis B or C infection as indicated by the presence of hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood
* ECG at screening that shows QTc \>450 ms when calculated using the Fridericia formula from either lead V3 or V4 \[86\]
* Use of:

  * Warfarin or warfarin-derivatives
  * HDACi
  * An agent definitely or possibly associated with effects on QT intervals within 2 weeks of screening
  * Drugs that induce or inhibit CYP3A4 or P-gp
* History of:

  * Clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for Torsades de pointes (e.g. heart failure)
  * Malignancy or transplantation, including skin cancers or Kaposi sarcoma
  * Diabetes mellitus
* Receipt of strong immunosuppressive or systemic chemotherapeutic agents within 28 days prior to study entry
* Known resistance to \>2 classes of ART
* Known hypersensitivity to the components of romidepsin, 3BNC117 or their analogues
* Women who are pregnant or breastfeeding, or with a positive pregnancy test during screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of non-estrogen containing contraceptions (according to the Danish Medicines Agency guidelines) to avoid pregnancy for the 3 week study period and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays
* Males or females who are unwilling or unable to use barrier contraception during sexual intercourse for the 3-week study period, and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays

Primary outcomes:
measure: Plasma HIV RNA kinetics
timeFrame: 3 months
measure: Quantification of the size of the proviral HIV reservoir
timeFrame: 1 year
measure: Time to viral rebound during ATI
timeFrame: 12 weeks
Secondary outcomes:
measure: Incidence of treatment emerging events (Safety and tolerability)
timeFrame: 1 year
measure: Quantification of the intact proviral DNA
timeFrame: 1 year
measure: Quantification of HIV mRNA and/or p24 positive cells
timeFrame: 30 days from study entry
measure: Immune reconstitution
timeFrame: 1 year
measure: Analytic treatment interruption (ATI) study
timeFrame: 64 weeks
measure: Impact of pre-ART virus sensitivity to 3BNC117 on ATI outcomes
timeFrame: Baseline and at viral rebound
measure: T cell mediated HIV specific immunity
timeFrame: First of 365 days
Other outcomes:
measure: Plasma cytokine and immune activation biomarker levels
timeFrame: 1 year
Locations:
city: Aalborg
country: Denmark
facility: Department of Infectious Diseases
city: Aarhus
country: Denmark
facility: Dept. of Infectious Diseases, Aarhus University Hospital
city: Hvidovre
country: Denmark
facility: Department of Infectious Diseases
city: København
country: Denmark
facility: Department of Infectious Diseases
city: Odense
country: Denmark
facility: Department of Infectious Diseases
city: London
country: United Kingdom
facility: Guy's and St Thomas'
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Aarhus University Hospital
name: Ole S Søgaard, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: