Back to resultsSafety, Tolerance and Antiretroviral Activity of Dasatinib: a Pilot Clinical Trial in Patients With Recent HIV-1 Infection (DASAHIVCURE)
Primary Purpose
Recent HIV-1 Infection
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Dasatinib
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Recent HIV-1 Infection
Eligibility Criteria
Inclusion Criteria:
- 18 to 65 years.
- Documented asymptomatic HIV-1 infection of 3-12 months duration (all patients must have a positive Western blot, including the p31 band whose appearance indicates infection of more than 90 days duration).
- Not having received ART
- CD4 T-lymphocyte count> 350 / μl
- Patient giving written informed consent
Exclusion Criteria:
- HBV positive serology (any marker except HBsAb after vaccination) or HCV positive RNA.
- ALT> 2 UNL, glomerular filtration rate <70 mL / 1.73 m2, leukocytes <4000 / mm3, total lymphocyte count <1000 / mm3, platelets <100,000 / mm3 or Hg <12g / dL.
- Pregnancy or active breastfeeding
- Ongoing or previous pleural effusion
- Chronic obstructive pulmonary disease, bronchial asthma or recent chest trauma.
- History of gastrointestinal or other bleeding.
- Any concomitant treatment with potentially dangerous drug interaction with dasatinib.
- Any clinical condition, at the opinion of the investigator, contraindicating participation (for example,
- Active neoplastic disease, active concomitant infection, etc.)
- Resistance to integrase inhibitors (raltegravir, dolutegravir, bictegravir) or analogues
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Dasatinib
Placebo
Arm Description
Dasatinib monotherapy (70 mg/day) will be given for 4 weeks. Antiretroviral therapy (ART) based on unboosted integrase inhibitors will be initiated at week 4 (S4) and dasatinib will be continued with ART until week 12.
Placebo monotherapy will be given for 4 weeks. Antiretroviral therapy (ART) based on unboosted integrase inhibitors will be initiated at week 4 (S4) and placebo will be continued with ART until week 12.
Outcomes
Primary Outcome Measures
Safety and tolerance of dasatinib with and without antiretroviral therapy, measured by number of AEs and SAEs
Measured by number of AEs and SAEs
Secondary Outcome Measures
Antiretroviral capacity of dasatinib
Measured by quantification of plasma HIV-1 viral load during 4-week administration of dasatinib monotherapy.
Changes in the viral reservoirs of patients with recent HIV-1 infection induced by dasatinib administration.
Measured by changes in the viral reservoirs (integrated DNA, genetically intact virus, residual and induced viral replication and determination of integration sites)
Changes in markers of inflammation and immune activation induced by dasatinib administration.
Measured by changes in ultra-sensitive CRP, IL6, TNF alpha and CD4/CD8, CD25, CD69, CD38, HLA-DR+.
Changes in SAMHD1 phosphorylation levels and cytotoxic activity against HIV-1 induced by dasatinib.
Measured by NK phenotyping and in vitro replication inhibition tests.
Pharmacokinetic interactions of coadministration non-boosted integrase inhibitor-based antiretroviral therapy with dasatinib.
Measured by Cmax
Pharmacokinetic interactions of coadministration non-boosted integrase inhibitor-based antiretroviral therapy with dasatinib.
Measured by Cmin
Impact of dasatinib on markers of senescence
Measured by expression in PBLs of beta-galactosidase, Bcl-2, Histone H2A, p16 and CD87.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05527418
Brief Title
Safety, Tolerance and Antiretroviral Activity of Dasatinib: a Pilot Clinical Trial in Patients With Recent HIV-1 Infection
Acronym
DASAHIVCURE
Official Title
Safety, Tolerance and Antiretroviral Activity of Dasatinib: a Pilot Clinical Trial in Patients With Recent HIV-1 Infection
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
April 2025 (Anticipated)
Study Completion Date
April 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Eva Bonfill
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Study to evaluate the safety, tolerability and antiretroviral activity of a new therapeutic strategy, based on the administration of dasatinib, an ITK, in patients with recent (3-12 months) asymptomatic HIV-1 infection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recent HIV-1 Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dasatinib
Arm Type
Experimental
Arm Description
Dasatinib monotherapy (70 mg/day) will be given for 4 weeks. Antiretroviral therapy (ART) based on unboosted integrase inhibitors will be initiated at week 4 (S4) and dasatinib will be continued with ART until week 12.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo monotherapy will be given for 4 weeks. Antiretroviral therapy (ART) based on unboosted integrase inhibitors will be initiated at week 4 (S4) and placebo will be continued with ART until week 12.
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Intervention Description
Dasatinib monotherapy 70 mg/day, during 16 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo during 16 weeks.
Primary Outcome Measure Information:
Title
Safety and tolerance of dasatinib with and without antiretroviral therapy, measured by number of AEs and SAEs
Description
Measured by number of AEs and SAEs
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Antiretroviral capacity of dasatinib
Description
Measured by quantification of plasma HIV-1 viral load during 4-week administration of dasatinib monotherapy.
Time Frame
at week 0 and 4
Title
Changes in the viral reservoirs of patients with recent HIV-1 infection induced by dasatinib administration.
Description
Measured by changes in the viral reservoirs (integrated DNA, genetically intact virus, residual and induced viral replication and determination of integration sites)
Time Frame
at week 0, 4, 16 and 52
Title
Changes in markers of inflammation and immune activation induced by dasatinib administration.
Description
Measured by changes in ultra-sensitive CRP, IL6, TNF alpha and CD4/CD8, CD25, CD69, CD38, HLA-DR+.
Time Frame
at week 0, 4, 16 and 52
Title
Changes in SAMHD1 phosphorylation levels and cytotoxic activity against HIV-1 induced by dasatinib.
Description
Measured by NK phenotyping and in vitro replication inhibition tests.
Time Frame
at week 0, 4, 16 and 52
Title
Pharmacokinetic interactions of coadministration non-boosted integrase inhibitor-based antiretroviral therapy with dasatinib.
Description
Measured by Cmax
Time Frame
at week 1, 2, 3, 4, 8, 12, 16
Title
Pharmacokinetic interactions of coadministration non-boosted integrase inhibitor-based antiretroviral therapy with dasatinib.
Description
Measured by Cmin
Time Frame
at week 1, 2, 3, 4, 8, 12, 16
Title
Impact of dasatinib on markers of senescence
Description
Measured by expression in PBLs of beta-galactosidase, Bcl-2, Histone H2A, p16 and CD87.
Time Frame
at week 0, 4, 16 and 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 to 65 years.
Documented asymptomatic HIV-1 infection of 3-12 months duration (all patients must have a positive Western blot, including the p31 band whose appearance indicates infection of more than 90 days duration).
Not having received ART
CD4 T-lymphocyte count> 350 / μl
Patient giving written informed consent
Exclusion Criteria:
HBV positive serology (any marker except HBsAb after vaccination) or HCV positive RNA.
ALT> 2 UNL, glomerular filtration rate <70 mL / 1.73 m2, leukocytes <4000 / mm3, total lymphocyte count <1000 / mm3, platelets <100,000 / mm3 or Hg <12g / dL.
Pregnancy or active breastfeeding
Ongoing or previous pleural effusion
Chronic obstructive pulmonary disease, bronchial asthma or recent chest trauma.
History of gastrointestinal or other bleeding.
Any concomitant treatment with potentially dangerous drug interaction with dasatinib.
Any clinical condition, at the opinion of the investigator, contraindicating participation (for example,
Active neoplastic disease, active concomitant infection, etc.)
Resistance to integrase inhibitors (raltegravir, dolutegravir, bictegravir) or analogues
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eva Bonfill
Phone
+34 932275400
Ext
4198
Email
bonfill@recerca.clinic.cat
12. IPD Sharing Statement
Learn more about this trial
Safety, Tolerance and Antiretroviral Activity of Dasatinib: a Pilot Clinical Trial in Patients With Recent HIV-1 Infection
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