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

Combining a TLR9 Agonist With Broadly Neutralizing Antibodies for Reservoir Reduction and Immunological Control of HIV Infection: An Investigator-initiated Randomized, Placebo-controlled, Phase IIa Trial.

Sponsors

Lead Sponsor: University of Aarhus

Collaborator: Aalborg University Hospital
Odense University Hospital
Rigshospitalet, Denmark
Hvidovre University Hospital
The Peter Doherty Institute for Infection and Immunity
University of Utah

Source University of Aarhus
Brief Summary

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

Overall Status Recruiting
Start Date May 6, 2019
Completion Date February 28, 2021
Primary Completion Date July 1, 2020
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Time to re-initiation of cART during analytical treatment interruption (ATI) Up to 26 weeks.
Secondary Outcome
Measure Time Frame
Safety and Tolerability assessment measured by AEs, Adverse Reactions (ARs), SAEs, Duration of the study
Plasma HIV RNA doubling time Duration of ATI (up to 26 weeks)
Enrollment 48
Condition
Intervention

Intervention Type: Drug

Intervention Name: Saline

Description: Placebo

Intervention Type: Drug

Intervention Name: Lefitolimod

Description: A TLR9 agonist administered s.c. once weekly for 8 weeks.

Other Name: MGN1703

Intervention Type: Drug

Intervention Name: 3BNC117 and 10-1074

Description: Broadly neutralizing antibodies against HIV env administered two times with a 3 week interval.

Other Name: RUhumab-001 and RUhumab-002

Eligibility

Criteria:

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)).

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

Gender: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Ole S Søgaard, MD PhD Principal Investigator Aarhus University Hospital
Overall Contact

Last Name: Ole S Søgaard, MD PhD

Phone: +45 78452842

Email: [email protected]

Location
Facility: Status: Contact:
Dept. of Internal Medicine, University of Utah | Salt Lake City, Utah, 84132, United States Not yet recruiting Adam M Spivak, MD
Alfred Hospital and Monash University | Melbourne, Australia Not yet recruiting Sharon Lewin, MD
Dept. of Infectious Diseases, Aalborg University Hospital | Aalborg, 9000, Denmark Not yet recruiting Henrik Nielsen, MD
Dept. of Infectious Diseases, Aarhus University Hospital | Aarhus, 8200, Denmark Recruiting Jesper F Højen, MD +45 40459718 [email protected]
Dept. of Infectious Diseases, Rigshospitalet | Copenhagen, 2100, Denmark Not yet recruiting Jan Gerstoft, MD
Dept. of Infectious Diseases, Amager and Hvidovre Hospitals | Hvidovre, 2650, Denmark Not yet recruiting Thomas Benfield, MD
Dept. of Infectious Diseases, Odense University Hospital | Odense, 5000, Denmark Not yet recruiting Isik S. Johansen, MD
Location Countries

Australia

Denmark

United States

Verification Date

January 2019

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Arm A: Placebo/Placebo

Type: Placebo Comparator

Description: This arm will receive placebo (sterile saline) for both Lefitolimod and 3BNC117 + 10-1074.

Label: Arm B: Lefitolimod/Placebo

Type: Active Comparator

Description: This arm will receive Lefitolimod and placebo (sterile saline) for 3BNC117 + 10-1074.

Label: Arm C: Placebo/3BNC117 + 10-1074

Type: Active Comparator

Description: This arm will receive 3BNC117 + 10-1074 and placebo (sterile saline) for Lefitolimod.

Label: Arm D: Lefitolimod/3BNC117 + 10-1074

Type: Active Comparator

Description: This arm will receive both Lefitolimod and 3BNC117 + 10-1074.

Acronym TITAN
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Factorial Assignment

Intervention Model Description: Participants will be randomized 1:1:1:1 in a blinded fashion to receive: Arm A: Placebo and Placebo Arm B: Lefitolimod and Placebo Arm C: Placebo and 3BNC117+10-1074 Arm D: Lefitolimod and 3BNC117+10-1074

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

Masking Description: The participant and all study personnel who directly interact with study participants are blinded to study arm designation.

Source: ClinicalTrials.gov