Clinical trial NCT03063788: Imaging the HIV Reservoir
Official title: Imaging the HIV Reservoir
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV
Lead sponsor: Bayside Health
Sponsor class: OTHER_GOV
Collaborators: name: The Peter Doherty Institute for Infection and Immunity
name: Monash University
name: Monash Health
name: Rockefeller University
name: Austin Health
First posted: 2017-02-24
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: DIAGNOSTIC

Brief summary: Radiolabelling broadly neutralizing anti-HIV antibody 3BNC117 with a Copper-64 radio isotope for infusion into people with HIV followed by MRI/PET scanning to detect HIV in vivo.

Detailed description: This study aims to develop a method to accurately image the size and location of HIV persistence in HIV-infected individuals. The project aims to combine the broadly neutralizing anti-HIV antibody 3BNC117 with a Copper-64 radio isotope for use in a clinical trial.

The clinical trial has three different stages. The first stage is to recruit two HIV uninfected individuals and determine the safety of 3 mg/kg of 3BNC117 combined with Copper-64 and MRI/PET scanning at 1, 24 and 48 hours post infusion. The second stage is to examine the distribution on MRI/PET of the 3BNC117-Copper-64 combination in four HIV-infected individuals with viremia who are not receiving antiretroviral therapy. The final stage is to perform the same intervention in aviremic people with HIV receiving antiretroviral therapy.

Eligibility criteria: Inclusion Criteria for All Groups:

* Age 18 to 65 years
* Able to give informed consent
* A female, may be eligible to participate if she:
* Is of non-child-bearing potential defined as either post-menopausal or incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
* Is of child-bearing potential with a negative pregnancy test at screening and agrees to use one of the following methods of contraception consistently and for at least 8 weeks after receiving the investigational drug :
* Complete abstinence from 2 weeks prior to investigational drug, and for at least 8 weeks after receiving the investigational drug
* Double barrier method
* Any intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year
* Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject
* Approved hormonal contraception
* Any other method with published data showing that the expected failure rate is \<1% per year

Group specific Inclusion criteria:

Group 1 (HIV-uninfected)

* A negative HIV Ag/Ab test at screening
* Amenable to HIV risk reduction counselling and agrees to maintain behaviour consistent with low risk of HIV exposure

Group 2 (HIV infected viremic off ART)

* Documented HIV-1 infection
* Not on ART for at least 8 weeks with HIV RNA plasma levels between 2,000 - 100,000 copies/ml
* Current CD4+ T cell counts \>300 cells/μL
* 3BNC117 sensitivity of subject derived HIV

Group 3 (HIV infected aviremic on ART)

* Documented HIV-1 infection
* Receiving combination ART for at least 12 months
* HIV-1 plasma RNA \<50 copies/mL for \> 12 months and \<20 copies/mL at screening. Episodes of a single HIV plasma RNA 50-500 copies/mL will not exclude participation if the subsequent HIV plasma RNA was \<50 copies/mL
* Current CD4+ T cell counts \>300 cells/μL

Exclusion Criteria for All Groups:

* Any clinically significant acute or chronic medical condition that in the opinion of the investigator would preclude participation (e.g. lymphoproliferative disorders or significant resections of the gastrointestinal tract that would interfere with the distribution of HIV tissue reservoirs)
* Receipt of a vaccination 14 days prior to receiving investigational drug
* Previous use of histone deacetylase inhibitors or other latency reversing agents
* Receipt of experimental HIV vaccine or monoclonal antibody therapy of any kind in the past
* History of Hepatitis B (Positive HBsAg) or Hepatitis C co-infection (Individuals with prior hepatitis C infection that is now cleared are eligible for enrolment)
* Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification
* Active alcohol or substance use that in the opinion of the investigator will prevent adequate compliance with study procedures
* Currently pregnant, breastfeeding or unwilling to use barrier contraception
* Women who are pregnant or breastfeeding or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy as specified in the inclusion criteria
* The following laboratory abnormalities:
* Absolute neutrophil count ≤1,300
* Hemoglobin ≤ 10 gm/dL
* Platelet count ≤125,000
* ALT ≥ 2.0 x ULN
* Total bilirubin ≥ 1.5 ULN
* Creatinine ≥ 1.1 x ULN

Primary outcomes:
measure: Comparisons of PET standard uptake values in regions of interest (gastrointestinal tract, lymph node groups, genital tract, and spleen) between the three groups (uninfected, viremic and aviremic infected)
timeFrame: 2 days
Secondary outcomes:
measure: Safety and tolerability (adverse events and assessment of laboratory parameters)
timeFrame: 2 weeks
measure: Comparisons of PET standard uptake values in regions of interest within each individual to radioactivity levels in a homogenous area of muscle to generate target to muscle ratios.
timeFrame: 2 days
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
Study officials:
References: