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Trial details imported from ClinicalTrials.gov

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




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

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
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases

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)
Timepoint [1] 0 0
Up to 26 weeks.
Secondary outcome [1] 0 0
Safety and Tolerability assessment measured by AEs, Adverse Reactions (ARs), SAEs,
Timepoint [1] 0 0
Duration of the study
Secondary outcome [2] 0 0
Plasma HIV RNA doubling time
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)).

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.
Minimum age
18 Years
Maximum age
65 Years
Sex
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/05/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2023
Sample size
Target
Accrual to date
Final
47
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
Country [7] 0 0
Norway
State/province [7] 0 0
Oslo

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
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Oslo University Hospital
Address [7] 0 0
Country [7] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual deidentified participant data (including data dictionaries) will be shared following the publication of the primary and secondary endpoints as outlined in this protocol. Data to be shared includes deidentified data points in published, peer-reviewed articles. Additional, related documents will also be available (study protocol, informed consent form, statistical analysis plan).

Supporting document/s available: Study protocol, Informed consent form (ICF)
When will data be available (start and end dates)?
Data will become available following publication of the specific dataset with no planned end date.
Available to whom?
Access to the data sharing will be given to researchers who provide a methodologically sound proposal for any type of analysis and requires IRB/Ethics committee approval (if applicable). Proposal should be addressed to [email protected]
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03837756