| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 |
To describe the change in retinol-binding protein/creatinine ratio with each regimen over 24 weeks.
|
|
| E.2.2 | Secondary objectives of the trial |
• To describe the change in retinol-binding protein/creatinine ratio with each regimen over 12 and 48 weeks.
• To assess the impact of each regimen on eGFR (C-G, MDRD, CKD-EPI with creatinine, CKD-EPI with cystatin-C), creatinine, plasma urate, β2- and alpha1-microglubulin excretion, urinary albumin and pro-tein/creatinine ratio, urinary cystatin-C / creatinine ratio, fractional phosphate excretion and rates of normoglycemic glycosuria throughout the study.
• To assess the efficacy of each regimen in achieving and maintaining viral suppression at weeks 4, 12, 24, 36 and 48 of therapy.
• To evaluate the impact of each regimen from baseline on immune markers (CD4+, CD8+, ratio) at 4, 12 , 24, 36 and 48 weeks of therapy.
• To evaluate the impact of each regimen from baseline on inflammatory markers (hsCRP, d-dimer, IL-6) at 4, 12, 24 and 48 weeks of therapy.
• To evaluate the impact of each regimen from baseline on metabolic markers: lipids at weeks 4, 12, 24, 36 and 48 of therapy |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patient volunteers who meet all of the following criteria are eligible for this trial:
1. Is male or female aged 18 years or above
2. Has documented HIV-1 infection
3. Has signed the Informed Consent Form voluntarily
4. Is willing to comply with the protocol requirements, including dosing schedules of each regimen
5. Has a HIV-plasma viral load at screening >1000 copies/mL
6. Has any CD4 cell count
7. Has never been exposed to ART (other than via PEP or PREP, not associated with acquisition of HIV)
8. Has an estimated glomerular filtration rate (MDRD method) >60 ml/min
9. Has no known resistance to TDF and FTC or to Integrase Inhibitors. HIV resistance test has to be dated no more than 1 year prior screening date. Only a RT/Pr gene resistance test is re-quired.
10. If female and of childbearing potential, she is using effective birth control methods (as agreed by the investigator) and is willing to continue practising these birth control methods during the trial and for at least 30 days after the end of the trial (or after last intake of investigational ARVs); Dosing of the OCP may need to be adjusted if randomized to the Stribild® arm.
Note: Women who are postmenopausal for least 2 years, women with total hysterectomy, and women who have a tubal ligation are considered of non-childbearing potential
11. If a heterosexually active male, he is using effective birth control methods and is willing to con-tinue practising these birth control methods during the trial and until follow-up visit
|
|
| E.4 | Principal exclusion criteria |
Patients meeting 1 or more of the following criteria cannot be selected:
1. Is infected with HIV-2
2. Is using any concomitant therapy disallowed as per SPC for the study drugs
3. Has a currently active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection-1993) with the following exceptions (must be discussed with the sponsor prior to enrolment):
▪ Stable cutaneous Kaposi’s Sarcoma (no pulmonary or gastrointestinal involvement other than oral lesions) unlikely to require systemic therapy during the trial period
▪ CD4 count less than 200 cells/mm3
Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed
4. Has diabetes or any known or established renal disease or abnormality regardless of if stable
5.Has presence at screening of proteinurea and or a urinary protein/creatinine ratio >30
6.Has untreated / not well controlled hypertension
7. Has acute viral hepatitis including, but not limited to, A, B, or C
8. Has chronic hepatitis B or chronic hepatitis C with AST and/or ALT >5 x ULN
Note: Subjects co-infected with chronic HCV (but not B) can enter the trial if clinically stable and not expected to require treatment during the trial period.
9. Has received any investigational drug within 30 days prior to the trial drug administration
10. No baseline resistance test to reverse transcriptase inhibitors available
11. Clinically significant allergy or hypersensitivity or other contraindication to any trial medication or excipients
12. If female, she is pregnant or breastfeeding
13. Screening blood results with any grade 3 / 4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 glucose, amylase or lipid elevation or asymptomatic grade 4 triglyceride elevation (re-test allowed).
12. Clinical or laboratory evidence of significantly decreased hepatic function or decompensation: INR > 1.5 or albumin < 30g/L
14. Any condition (including drug/alcohol abuse) or laboratory results which, in the investigator’s opinion, interfere with assessments or completion of the trial.
15. Is not using high protein training supplements such as creatinine or intermittently following exclusionary or high protein diets
16. Is not receiving medication with known relevant drug interactions or contraindications to any of the trial medications
17. Has untreated/not well controlled hypertension (values of BP consistently > 150/95 mmHg). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary endpoint:
• The change in retinol-binding protein/creatinine ratio (PCR) with each regimen over 24 weeks.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| When all patients have reached 24 weeks |
|
| E.5.2 | Secondary end point(s) |
• The change in retinol-binding pro-tein/creatinine ratio (PCR) with each regi-men over 12 and 48 weeks.
• The variation from baseline of eGFR (C-G, MDRD, CKD-EPI with creatinine /cystatin-C), creatinine, cystatin-C, β2- and alpha1- microglubulin excretion, urinary albumin and protein/creatinine ratio, urinary creatinine / cystatin-C ratio, fractional phosphate excretion (fasted plasma phosphate and urinary spot phosphate), plasma urate and rates of normoglycemic glycosuria on each regimen, at 4, 12, 24, and 48 weeks of therapy.
• The proportion of patients achieving viro-logic response (HIV RNA <40 cp/mL) at week 4, 12, 24, 36 and 48.
• The changes in immunologic markers (CD4+, CD8+, ratio) from baseline at weeks 4, 12, 24, 36 and 48 of therapy with each regimen.
• The changes in inflammatory markers (hsCRP, IL-6, d-dimer) from baseline at weeks 4, 12, 24 and 48 of therapy with each regimen.
• The changes from baseline in metabolic markers: lipids (TC, LDL, HDL, TGs) at weeks 4, 12, 24, 36 and 48 of therapy, and on insulin, fasting glucose, HOMA-i at 24 weeks of therapy.
• Tenofovir concentration (C.trough 12 or 24) in plasma and urine, at week 4 of treatment with each regimen and elvitegravir/cobicistat or dolutegravir concentrations (at any time post dose as c24 will be calculated by mathematical modelling) in plasma at week 4 of treatment in the stribild and dolutegravir arms
• Relationship between genetic polymorphisms and exposure to the studied drugs
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| When all patients have reached 48 weeks |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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 | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| 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
|
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 1 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 1 |
Print
