A Prospective, Randomized, Open Study on the Efficacy and Safety of the GnRH Analogue Triptorelin for HIV-1 Reservoir Reduction in ART Treated HIV-1 Infected Patients

Immune System Regulation AB5 sites in 2 countries52 target enrollmentSeptember 19, 2018

ConditionsHIV-1-infection

InterventionsTriptorelin acetate depot

DrugsTriptorelin acetate depot

Overview

Phase: Phase 2
Intervention: Triptorelin acetate depot
Conditions: HIV-1-infection
Sponsor: Immune System Regulation AB
Enrollment: 52
Locations: 5
Primary Endpoint: Mean change from baseline to week 12 in total HIV-1 DNA levels in CD4+ cells in the active group compared to the mean change in the control group.
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

An open, randomised, parallel arm phase IIa study. 52 HIV-1 infected patients will be randomised (in a 1:1 ratio) to either an active group or a control group. The active group will receive the GnRH analogue triptorelin depot monthly at baseline, week 4 and week 8. Patients in the active group and in the control group will continue their triple combination antiretroviral therapy (ART) during the study without changes; unless there is rationale for change on medical ground. In order to prevent the negative effects of a low testosterone level, patients in the active group will be offered to receive a single intramuscular depot injection of testosterone approximately 7 days after triptorelin treatment. This depot administration will keep the serum testosterone on a normal level until the next triptorelin dose. This will be repeated when triptorelin is administered at week 4 and week 8. Total study period is 24 weeks.

Registry

clinicaltrials.gov

Start Date

September 19, 2018

End Date

December 2021

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Male

Investigators

Sponsor

Immune System Regulation AB

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male gender
•18 to 65 years of age, inclusive, at the time of informed consent
•Ability and willingness to give a written or orally witnessed informed consent
•HIV-1 infection as documented by HIV antibody test
•CD4+ cell count \>300 cells/μL at screening
•Total HIV-1 DNA level between 100 to 5000 copies/million PBMC as measured by real-time PCR within 4 months prior to screening
•Plasma HIV-1 RNA level \<50 copies/mL for the last year (one blip allowed; blip defined as HIV RNA between 50-150 copies/mL) including a plasma HIV-1 RNA level \<50 copies/mL at screening
•On triple combination ART (two nucleoside reverse transcriptase inhibitors (NRTI) + one integrase inhibitor or protease inhibitor or one non-NRTI (NNRTI)) for minimum 36 months (assessed at screening)
•Currently on continuous triple combination ART as specified above (i.e. no changes in medication) the past 4 months prior to screening

Exclusion Criteria

•Treatment failure while on triple ART
•Nadir CD4+ count \< 200 cells/μL
•History of any immunodeficiency disease or condition other than HIV, chronic clinically significant illness or autoimmune disease
•Known positive result of screening for hepatitis B (surface antigen positive or detectable HBV DNA levels in blood) or hepatitis C (HCV RNA positive). Patient treated for HCV and assessed as cured by treating physician is eligible for the study
•Serious ongoing infection
•Abnormal liver biochemical tests \> 2 x upper limit of normal (ULN) of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase (ALP)
•Total testosterone, LH or FSH levels at screening assessed as clinically abnormal by the Investigator
•Current treatment with testosterone
•History of any clinically significant kidney disease as determined by the Investigator or eGFR \< 60 mL/min/1.73 m2 at screening. (Patients on dolutegravir with an eGFR\<60 may be verified for study inclusion by analysis of cystatin C that should then be assessed as normal by the Investigator in order for the patient to be eligible)
•Diabetes mellitus or a fasting plasma blood glucose \>7.0 mmol/L at screening

Arms & Interventions

Triptorelin (GnRH analogue)

Intervention: Triptorelin acetate depot

Outcomes

Primary Outcomes

Mean change from baseline to week 12 in total HIV-1 DNA levels in CD4+ cells in the active group compared to the mean change in the control group.

Time Frame: Baseline to 12 weeks time point

Secondary Outcomes

Number of adverse events in active group compared to control group(Baseline to 12 weeks time point)
Mean change in the CD8+ T-cell counts from baseline to week 12 in the active group compared to the mean change in the control group.(Baseline to 12 weeks time point)
Mean change of the HLA class 1 expression from baseline to week 12 in the active group compared to the mean change in the control group(Baseline to 12 weeks time point)
Mean change in the CD4+ T-cell counts from baseline to week 12 in the active group compared to the mean change in the control group.(Baseline to 12 weeks time point)
Number and percentage of patients reporting any adverse events in active group compared to control group(Baseline to 12 weeks time point)