E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020161 |
E.1.2 | Term | HIV infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate the efficacy of 12 weeks of triptorelin depot treatment in ART treated HIV-1 infected male patients (active group) compared to HIV-1 infected male patients on ART only (control group). |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the safety and tolerability of 12 weeks of triptorelin depot treatment in ART treated HIV-1 infected male patients (active group) compared to HIV-1 infected male patients on ART only (control group). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 informed consent. A signed informed consent must be available prior to any study-related procedures. 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
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E.4 | Principal 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. For Germany: Positive antibody test for hepatitis B at screening. Positive antibody test for hepatitis C (HCV) at screening unless the patient has been treated for HCV and assessed as cured by the treating physician (including an HCV RNA negative test) 5. Serious ongoing infection, including SARS-CoV-2 infection (checked by body temperature control and interview form). 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. An increased PSA (Prostate Specific Antigen) value that is assessed as abnormal by the treating physician 16. Involvement in any other drug study within 30 days prior to this study entry 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. 19. Condition or concomitant anti-coagulation treatment making intramuscular injections contraindicated (note that treatment with acetylsalicylic acid is permitted). 20. For Germany: Person concerned has been admitted to an institution by virtue of an order issued either by the judicial or the administrative authorities. 21. For Germany: CRO or Sponsor employees or employees under the direct supervision of the Investigator or the investigational sites and/or involved directly in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the mean change from baseline to week 12 in the levels of total HIV-1 DNA levels in CD4+ cells in the active group compared to the mean change in the control group. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 12 assessment versus baseline |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are to evaluate the: • 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. • 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. • 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.
The following safety parameters will be used to address the safety and tolerability portion of the secondary objectives: • adverse events (AEs) and serious adverse events (SAEs), safety laboratory test results, physical examination findings and vital signs results.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy endpoints: week 12 assessment versus baseline Safety endpoints: all timepoints versus baseline |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
The exploratory blood samples taken at baseline and week 12 will be used for biomarker research in the field of HIV and/or GnRH related research (see section 10.4.3 in study protocol). |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Comparator is no treatment (only ART) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |