History of Changes for Study: NCT03837756

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

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Study Record Versions

Version	Submitted Date	Changes
1	February 8, 2019	None (earliest Version on record)
2	April 24, 2019	Study Status
3	May 6, 2019	Recruitment Status, Study Status and Contacts/Locations
4	April 15, 2021	Contacts/Locations, Study Status, Eligibility and Sponsor/Collaborators
5	November 3, 2021	Contacts/Locations and Study Status
6	March 30, 2022	Recruitment Status, Contacts/Locations, Study Status and Study Design
7	May 22, 2023	Recruitment Status and Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	TITAN-001
Brief Title:	Combining TLR9 Agonist With bNAbs for Reservoir Reduction and Immunological Control of HIV (TITAN)
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.
Secondary IDs:	2018-001165-16 [EudraCT Number] AGR-2016-8833 [Other Grant/Funding Number: Gilead Sciences, Inc.]

Study Status


Record Verification:	January 2019
Overall Status:	Not yet recruiting
Study Start:	March 1, 2019
Primary Completion:	July 1, 2020 [Anticipated]
Study Completion:	February 28, 2021 [Anticipated]

First Submitted:	February 7, 2019
First Submitted that Met QC Criteria:	February 8, 2019
First Posted:	February 12, 2019 [Actual]

Last Update Submitted that Met QC Criteria:	February 8, 2019
Last Update Posted:	February 12, 2019 [Actual]

Sponsor/Collaborators


Sponsor:	University of Aarhus
Responsible Party:	Sponsor
Collaborators:	Aalborg University Hospital Odense University Hospital Rigshospitalet, Denmark Hvidovre University Hospital The Peter Doherty Institute for Infection and Immunity University of Utah

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description


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
Detailed Description:

Conditions


Conditions:	HIV-1-infection
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 2
Interventional Study Model:	Factorial Assignment
	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
Number of Arms:	4
Masking:	Double (Participant, Investigator)
Allocation:	Randomized
Enrollment:	48 [Anticipated]

Arms and Interventions

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 Names: 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 Names: 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 Names: MGN1703 Drug: 3BNC117 and 10-1074 Broadly neutralizing antibodies against HIV env administered two times with a 3 week interval. Other Names: RUhumab-001 and RUhumab-002

Outcome Measures


Primary Outcome Measures:
1.	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:
1.	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)
2.	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)

Eligibility


Minimum Age:	18 Years
Maximum Age:	65 Years
Sex:	All
Gender Based:
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/Locations


Central Contact Person:	Ole S Søgaard, MD PhD Telephone: +45 78452842 Email: olesoega@rm.dk
Central Contact Backup:	Jesper F Højen, MD Telephone: +45 40459718 Email: jephns@rm.dk
Study Officials:	Ole S Søgaard, MD PhD Principal Investigator Aarhus University Hospital
Locations:	United States, Utah
	Dept. of Internal Medicine, University of Utah Salt Lake City, Utah, United States, 84132 Contact:Contact: Adam M Spivak, MD
	Australia
	Alfred Hospital and Monash University Melbourne, Australia Contact:Contact: Sharon Lewin, MD Contact:Contact: Thomas A Rasmussen, MD
	Denmark
	Dept. of Infectious Diseases, Aalborg University Hospital Aalborg, Denmark, 9000 Contact:Contact: Henrik Nielsen, MD
	Dept. of Infectious Diseases, Aarhus University Hospital Aarhus, Denmark, 8200 Contact:Contact: Jesper F Højen, MD +45 40459718 jephns@rm.dk
	Dept. of Infectious Diseases, Rigshospitalet Copenhagen, Denmark, 2100 Contact:Contact: Jan Gerstoft, MD
	Dept. of Infectious Diseases, Amager and Hvidovre Hospitals Hvidovre, Denmark, 2650 Contact:Contact: Thomas Benfield, MD
	Dept. of Infectious Diseases, Odense University Hospital Odense, Denmark, 5000 Contact:Contact: Isik S. Johansen, MD

IPDSharing


Plan to Share IPD:	Yes 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 Information: Study Protocol Informed Consent Form (ICF)
	Time Frame: Data will become available following publication of the specific dataset with no planned end date.
	Access Criteria: 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 olesoega@rm.dk
	URL:

References


Citations:
Links:
Available IPD/Information: