Clinical Trials

MainTitle

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

This study is currently recruiting participants. (see Contacts and Locations)

Verified January 2019 by University of Aarhus

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

Information provided by (Responsible Party)
University of Aarhus
ClinicalTrials.gov Identifier
NCT03837756

First received: February 7, 2019
Last updated: May 6, 2019
Last Verified: January 2019
History of Changes
Purpose

Purpose

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

Condition Intervention Phase
HIV-1-infection

Drug : Saline
Drug : Lefitolimod
Drug : 3BNC117 and 10-1074
Phase 2

Study Type: Interventional
Study Design: 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
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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.

Further study details as provided by University of Aarhus:

Primary Outcome Measures

  • Time to re-initiation of cART during analytical treatment interruption (ATI) [ Time Frame: Up to 26 weeks. ]
    Time from date of cART cessation to the date of the last of three consecutive plasma HIV-1 RNA measurements >10,000 copies/mL, CD4 cell count <350 on two consecutive measurements, or end of ATI (i.e. 26 weeks after cessation of cART) - whichever comes first.
Secondary Outcome Measures:
  • Safety and Tolerability assessment measured by AEs, Adverse Reactions (ARs), SAEs, [ Time Frame: Duration of the study ]
    Subject who receives at least one dose of the IMP(s) will be included in the evaluation for safety, measured by AEs, Adverse Reactions (ARs), SAEs, Serious ARs (SARs) and (SUSAR)
  • Plasma HIV RNA doubling time [ Time Frame: Duration of ATI (up to 26 weeks) ]
    Plasma HIV RNA doubling time from first measurement >50 copies/mL to first measurement >1,000 copies/mL during the analytical treatment interruption (plasma HIV RNA measured by standard clinical assays, e.g. Cobas TaqMan; Lower limit of quantitation 20 copies/mL)

Estimated Enrollment: 48
Study Start Date: May 6, 2019
Estimated Study Completion Date: February 28, 2021
Estimated Primary Completion Date: July 1, 2020 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Placebo Comparator: Arm A: Placebo/Placebo
This arm will receive placebo (sterile saline) for both Lefitolimod and 3BNC117 + 10-1074.
Drug: Saline

Placebo

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

Placebo

Drug: Lefitolimod

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

Other Name: MGN1703
Active Comparator: Arm C: Placebo/3BNC117 + 10-1074
This arm will receive 3BNC117 + 10-1074 and placebo (sterile saline) for Lefitolimod.
Drug: Saline

Placebo

Drug: 3BNC117 and 10-1074

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

Other Name: RUhumab-001 and RUhumab-002
Active Comparator: Arm D: Lefitolimod/3BNC117 + 10-1074
This arm will receive both Lefitolimod and 3BNC117 + 10-1074.
Drug: Lefitolimod

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

Other Name: MGN1703
Drug: 3BNC117 and 10-1074

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

Other Name: RUhumab-001 and RUhumab-002
Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 65 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

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

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03837756

Contacts

Contact:   Ole S Søgaard, MD PhD +45 78452842 olesoega@rm.dk
Contact:   Jesper F Højen, MD +45 40459718 jephns@rm.dk

Locations

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

Sponsors and Collaborators

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

Investigators

Principal Investigator: Ole S Søgaard, MD PhD Aarhus University Hospital
More Information

More Information


Responsible Party: University of Aarhus  
ClinicalTrials.gov Identifier: NCT03837756   History of Changes  
Other Study ID Numbers: TITAN-001  
  2018-001165-16  
  AGR-2016-8833  
Study First Received: February 7, 2019  
Last Updated: May 6, 2019  
Individual Participant Data    
Plan to Share IPD: Yes  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  
Product Manufactured in and Exported from the U.S.: Yes  

Additional relevant MeSH terms:
Infection
Antibodies, Blocking

ClinicalTrials.gov processed this data on September 18, 2019
This information is provided by ClinicalTrials.gov.