Efficacy and Safety of GnRH Analogue Triptorelin for HIV-1 Reservoir Reduction in ART Treated HIV-1 Infected Patients

NCT03536234 | Unknown Phase 2

• 1 other identifier: ISR-003
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 5

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.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to 12 weeks time point

Secondary Outcomes (5)

• 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

• 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

• Number of adverse events in active group compared to 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

Study Arms (2)

Triptorelin (GnRH analogue)

EXPERIMENTAL

Drug: Triptorelin acetate depot

Control group

NO INTERVENTION

Interventions

Triptorelin acetate depot DRUG

3.75 mg triptorelin depot (monthly injections). 3 doses in total

Triptorelin (GnRH analogue)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male gender
• 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

You may not qualify if:

• 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
• Diabetes mellitus or a fasting plasma blood glucose \>7.0 mmol/L at screening
• Intolerance or contraindication to injectable triptorelin
• Vital signs, physical examination or lab results that exhibit evidence of acute illness
• Known history of moderate or severe depression (see definitions in ICD-10) within the past 5 years
• Any congenital or acquired prolongation of the QTc interval and use of any drugs that has been proven to prolong the QTc interval (Normal QTc interval defined as \<450 msec)
• Involvement in any other drug study within 30 days prior to this study entry
• An increased PSA (Prostate Specific Antigen) value that is assessed as abnormal by the treating physician

Sponsors & Collaborators

• Immune System Regulation AB: lead

Study Sites (5)

Zentrum für Infektiologie Berlin Prenzlauer Berg

Berlin, 10439, Germany

RECRUITING

MVZ Karlsplatz

Munich, 80335, Germany

RECRUITING

Östra sjukhuset

Gothenburg, 416 50, Sweden

RECRUITING

Södersjukhuset

Stockholm, 118 83, Sweden

RECRUITING

Karolinska University Hospital Huddinge

Stockholm, 141 86, Sweden

RECRUITING

Study Officials

• Ola Winqvist, MD, PhD

  ISR AB

  STUDY DIRECTOR

Central Study Contacts

Ola Winqvist, MD, PhD

CONTACT

+46-70-5427939; ola.winqvist@israb.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2018
• First Posted: May 24, 2018
• Study Start: September 19, 2018
• Primary Completion: August 1, 2021
• Study Completion: December 1, 2021
• Last Updated: January 13, 2021

Record last verified: 2021-01

Locations

DE (2); SE (3)