The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03837756




Registration number
NCT03837756
Ethics application status
Date submitted
7/02/2019
Date registered
12/02/2019
Date last updated
7/05/2019

Titles & IDs
Public title
Combining TLR9 Agonist With bNAbs for Reservoir Reduction and Immunological Control of HIV
Scientific 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.
Secondary ID [1] 0 0
2018-001165-16
Secondary ID [2] 0 0
TITAN-001
Universal Trial Number (UTN)
Trial acronym
TITAN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV-1-infection 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Saline
Treatment: Drugs - Lefitolimod
Treatment: Drugs - 3BNC117 and 10-1074

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

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

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

Active Comparator: Arm D: Lefitolimod/3BNC117 + 10-1074 - This arm will receive both Lefitolimod and 3BNC117 + 10-1074.


Treatment: Drugs: Saline
Placebo

Treatment: Drugs: Lefitolimod
A TLR9 agonist administered s.c. once weekly for 8 weeks.

Treatment: Drugs: 3BNC117 and 10-1074
Broadly neutralizing antibodies against HIV env administered two times with a 3 week interval.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to re-initiation of cART during analytical treatment interruption (ATI) - 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.
Timepoint [1] 0 0
Up to 26 weeks.
Secondary outcome [1] 0 0
Safety and Tolerability assessment measured by AEs, Adverse Reactions (ARs), SAEs, - 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)
Timepoint [1] 0 0
Duration of the study
Secondary outcome [2] 0 0
Plasma HIV RNA doubling time - 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)
Timepoint [2] 0 0
Duration of ATI (up to 26 weeks)

Eligibility
Key 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)).
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Factorial
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Alfred Hospital and Monash University - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Utah
Country [2] 0 0
Denmark
State/province [2] 0 0
Aalborg
Country [3] 0 0
Denmark
State/province [3] 0 0
Aarhus
Country [4] 0 0
Denmark
State/province [4] 0 0
Copenhagen
Country [5] 0 0
Denmark
State/province [5] 0 0
Hvidovre
Country [6] 0 0
Denmark
State/province [6] 0 0
Odense

Funding & Sponsors
Primary sponsor type
Other
Name
University of Aarhus
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Aalborg University Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Odense University Hospital
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Rigshospitalet, Denmark
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Hvidovre University Hospital
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
The Peter Doherty Institute for Infection and Immunity
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
University of Utah
Address [6] 0 0
Country [6] 0 0

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT03837756
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ole S Søgaard, MD PhD
Address 0 0
Aarhus University Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ole S Søgaard, MD PhD
Address 0 0
Country 0 0
Phone 0 0
+45 78452842
Fax 0 0
Email 0 0
olesoega@rm.dk
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03837756