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

NCT ID: NCT03536234

Last Updated: 2021-01-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-19
• Study Completion Date: 2021-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Triptorelin (GnRH analogue)

Group Type: EXPERIMENTAL

Triptorelin acetate depot

Intervention Type: DRUG

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

Control group

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Triptorelin acetate depot

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male gender

2. 18 to 65 years of age, inclusive, at the time of informed consent

3. Ability and willingness to give a written or orally witnessed informed consent

4. HIV-1 infection as documented by HIV antibody test

5. CD4+ cell count >300 cells/μL at screening

6. Total HIV-1 DNA level between 100 to 5000 copies/million PBMC as measured by real-time PCR within 4 months prior to screening

7. 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

8. 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)

9. Currently on continuous triple combination ART as specified above (i.e. no changes in medication) the past 4 months prior to screening

Exclusion Criteria

1. Treatment failure while on triple ART

2. Nadir CD4+ count < 200 cells/μL

3. History of any immunodeficiency disease or condition other than HIV, chronic clinically significant illness or autoimmune disease

4. 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

5. Serious ongoing infection

6. Abnormal liver biochemical tests > 2 x upper limit of normal (ULN) of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase (ALP)

7. Total testosterone, LH or FSH levels at screening assessed as clinically abnormal by the Investigator

8. Current treatment with testosterone

9. 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)

10. Diabetes mellitus or a fasting plasma blood glucose >7.0 mmol/L at screening

11. Intolerance or contraindication to injectable triptorelin

12. Vital signs, physical examination or lab results that exhibit evidence of acute illness

13. Known history of moderate or severe depression (see definitions in ICD-10) within the past 5 years

14. 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)

15. Involvement in any other drug study within 30 days prior to this study entry

16. An increased PSA (Prostate Specific Antigen) value that is assessed as abnormal by the treating physician

17. Any medical condition that in the opinion of the Investigator would compromise the patient's ability to participate in the study

18. Investigator considers the patient unlikely to comply with study procedures, restrictions and requirements.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Immune System Regulation AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ola Winqvist, MD, PhD

Role: STUDY_DIRECTOR

ISR AB

Locations

Zentrum für Infektiologie Berlin Prenzlauer Berg

Berlin, , Germany

Site Status: RECRUITING

MVZ Karlsplatz

Munich, , Germany

Site Status: RECRUITING

Östra sjukhuset

Gothenburg, , Sweden

Site Status: RECRUITING

Södersjukhuset

Stockholm, , Sweden

Site Status: RECRUITING

Karolinska University Hospital Huddinge

Stockholm, , Sweden

Site Status: RECRUITING

Countries

Germany; Sweden

Central Contacts

Ola Winqvist, MD, PhD

Role: CONTACT

ola.winqvist@israb.se

+46-70-5427939

Facility Contacts

Jukka Hartikainen, MD

Role: primary

hartikainen@zibp.de

Jukka Hartikainen, MD

Role: primary

hartikainen@zibp.de

Piotr Nowak, MD PhD

Role: primary

Piotr.Nowak@ki.se

Piotr Nowak, MD PhD

Role: primary

Piotr.Nowak@ki.se

Piotr Nowak, MD PhD

Role: primary

Piotr.Nowak@ki.se

Other Identifiers

ISR-003

Identifier Type: -

Identifier Source: org_study_id