Combining TLR9 Agonist With bNAbs for Reservoir Reduction and Immunological Control of HIV (TITAN)

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University of Aarhus

Status and phase

Completed
Phase 2

Conditions

HIV-1-infection

Treatments

Drug: 3BNC117 and 10-1074
Drug: Lefitolimod
Drug: Saline

Study type

Interventional

Funder types

Other

Identifiers

NCT03837756
2018-001165-16 (EudraCT Number)
TITAN-001
AGR-2016-8833 (Other Grant/Funding Number)

Details and patient eligibility

About

This study is designed to evaluate the safety and efficacy of lefitolimod and 3BNC117/10-1074 in HIV-1-infected individuals on ART and during ATI as intervention to reduce the HIV-1 reservoir

Enrollment

47 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Documented HIV-1 infection
  • Adults age 18-65 years
  • On ART for a minimum of 18 months.
  • CD4+ T cell count >500 at screening
  • HIV-1 RNA plasma level of < 50 copies/mL by standard assays for at least 15 months (a single viral load measurement > 50 but < 500 copies/mL during this time period is allowable).
  • Able to give informed consent
  • Viral reservoir sensitivity to 3BNC117 and 10-1074. (Sensitivity of the viral reservoir to neutralization by 3BNC117 and 10-1074 will be tested following the screening visit (i.e. prior to randomization)).

Sensitivity of the viral reservoir to neutralization by 3BNC117 and 10-1074 will be tested following the screening visit (i.e. prior to enrollment and randomization). Isolated PBMCs will be analyzed using the PhenoSense HIV mAb Assay, Monogram Biosciences. The sensitivity of an individuals archieved proviruses to bNAb neutralization will be determined by the IC50 value of PBMC derived pseudovirus inhibition. Subjects that are considered sensitive to both 3BNC117 (IC90<=1.5 μg/mL) and 10-1074 (IC90<=2.0 μg/mL) AND MPI>97 AND fulfill the other inclusion/exclusion criteria will proceed to study enrolment and randomization.

If sensitivity cannot be determined by the PhenoSense HIVmAb Assay, participants will be screened for 3BNC117 and 10-1074 sensitivity using HIV env sequencing carried out in-house (Aarhus, Denmark). The method was originally established and validated by Rockefeller University that already has this method implemented. The method utilizes HIV-1 DNA envelope sequencing and a mathematical prediction binding algoritm of known binding sites of the antibodies. Based on the individual HIV env sequence, proviruses are categorized as "sensitive" or "resistant". Subjects that are determined to be sensitive to both 3BNC117 and 10-1074 (defined as at least 90% of known sequences sensitive to either bNAb) AND fulfill the other inclusion/exclusion criteria will proceed to study enrolment and randomization.

Exclusion criteria

  • Any significant acute medical illness requiring hospitalization in the past 4 weeks
  • Any evidence of an active AIDS-defining opportunistic infection
  • Any condition that, in the Investigator's opinion, will prevent adequate compliance with study therapy
  • The following laboratory values at screening, 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) ≤50 mL/min (based on serum creatinine) // Platelet count ≤100 x109/L // Absolute neutrophil count ≤1x109/L
  • Hepatitis B or C infection
  • History of: Malignancy, excluding non-melanoma skin cancers, or organ transplantation
  • 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 lefitolimod, 3BNC117, 10-1074 or their analogues
  • Pre-existing autoimmune or antibody-mediated diseases
  • Women who are pregnant or breastfeeding, or unwilling/ unable to use an acceptable method of contraception (if of child bearing potential)
  • Males or females who are unwilling or unable to use barrier contraception during sexual intercourse until plasma HIV-1 RNA is undetectable using standard assays

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Factorial Assignment

Masking

Double Blind

47 participants in 4 patient groups, including a placebo group

Arm A: Placebo/Placebo
Placebo Comparator group
Description:
This arm will receive placebo (sterile saline) for both Lefitolimod and 3BNC117 + 10-1074.
Treatment:
Drug: Saline
Arm B: Lefitolimod/Placebo
Active Comparator group
Description:
This arm will receive Lefitolimod and placebo (sterile saline) for 3BNC117 + 10-1074.
Treatment:
Drug: Saline
Drug: Lefitolimod
Arm C: Placebo/3BNC117 + 10-1074
Active Comparator group
Description:
This arm will receive 3BNC117 + 10-1074 and placebo (sterile saline) for Lefitolimod.
Treatment:
Drug: Saline
Drug: 3BNC117 and 10-1074
Arm D: Lefitolimod/3BNC117 + 10-1074
Active Comparator group
Description:
This arm will receive both Lefitolimod and 3BNC117 + 10-1074.
Treatment:
Drug: Lefitolimod
Drug: 3BNC117 and 10-1074

Trial contacts and locations

8

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Data sourced from clinicaltrials.gov

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