E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus (HIV-1) Infection in Subjects on Chronic Hemodialysis |
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E.1.1.1 | Medical condition in easily understood language |
Human Immunodeficiency Virus (HIV-1) Infection in Subjects on Chronic Hemodialysis |
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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 | LLT |
E.1.2 | Classification code | 10068341 |
E.1.2 | Term | HIV-1 infection |
E.1.2 | System Organ Class | 100000004862 |
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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 |
To evaluate the safety and tolerability of the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF; E/C/F/TAF) fixed dose combination (FDC) in HIV-1 infected adults with end stage renal disease (ESRD) on chronic hemodialysis (HD) at Week 48 |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of the EVG/COBI/FTC/TAF
(E/C/F/TAF FDC) in HIV-1 infected adults with ESRD on chronic HD at
week 96
- To evaluate the proportion of subjects achieving virologic response (defined as HIV-1 RNA < 50 copies/mL, Snapshot analysis) at Weeks 24, 48 and 96
- To evaluate plasma pharmacokinetics (PK) of EVG, COBI, FTC, TAF and TFV in HIV-1 infected patients with ESRD on chronic HD |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetic (PK) Sub-study : All subjects who provide consent will be eligible to participate in the PK sub-study (target n=15). For the PK sub-study, intense blood sampling will be conducted at or between Week 2 or Week 4 study visits, on a day prior to the day of hemodialysis and when the subject has administered three doses of E/C/F/TAF between two hemodialysis sessions. The PK of EVG, COBI, FTC, TAF and TFV will be evaluated. Study drug administration will be observed in-clinic at the sub-study visit. |
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E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:
1) The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of screening procedures;
2) Age ≥ 18 years;
3) Currently receiving a stable ARV regimen for ≥ 6 consecutive months prior to screening;
4) Documented plasma HIV-1 RNA concentrations < 50 copies/mL for at least 6 months preceding the screening visit measured at least twice using the same assay) and have HIV-1 RNA < 50 copies/mL at screening; a) In the preceding 6 months prior to screening, one episode of “blip” (HIV-1 RNA ≥ 50 copies/mL and < 400 copies/mL) is acceptable, only if HIV-1 RNA is < 50 copies/mL immediately before and after the blip. b) To determine virologic suppression in the preceding 6 months prior to screening, the lower limit of quantification (LLOQ) by the local HIV-1 RNA assay may be used, only if its LLOQ is greater than 50 copies/mL (e.g. LLOQ of 75 copies/mL);
5 )No documented history of HIV-1 resistance to EVG, FTC, 3TC or TFV and no history of switching off EVG, FTC, 3TC or TFV due to concern for resistance;
6) CD4+ T cell count of ≥ 200 cells/μL;
7) ESRD with eGFR < 15 mL/min by Cockcroft-Gault formula for creatinine clearance;
8) On chronic HD for ≥ 6 months prior to screening;
9) Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN);
10) Chronic Hepatitis C (HCV) infection allowed if liver function is stable (see above for criteria);
11) Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm3; platelets ≥ 50,000/mm3; hemoglobin ≥ 8.5 g/dL);
12) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN);
13) A female subject is eligible to enter the study if it is confirmed that she is: a) Not pregnant confirmed by a negative serum pregnancy test (unless permanently sterile or greater than two years post-menopausal); b) Of non-child bearing potential (i.e. women who have had a hysterectomy, have had both ovaries removed or medically documented ovarian failure, or are postmenopausal women > 54 years of age with cessation (for ≥ 12 months) of previously occurring menses Female subjects who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory Reference range. c) Of childbearing potential and agrees to utilize the protocol specified method of contraception or be non-heterosexually active or practice abstinence from screening throughout the duration of the study treatment and for 30 days following study drug discontinuation; d) Female subjects who utilize hormonal contraception as one of the birth control methods must have used the same method for at least three months prior to the study dosing.
14) Male subjects must agree to use protocol specified method(s) of contraception from screening throughout the duration of study treatment and for 30 days following discontinuation of study drugs.
15) Male subjects must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.
16) Lactating females must agree to discontinue nursing before the study drug is administered. |
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study :
1) Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.);
2) Hepatitis B surface antigen (HBsAg) positive;
3) Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening;
4) Treatment with radiation, cytotoxic chemotherapeutic agents, or any immunomodulator within 30 days of screening;
5) Any other clinical history, condition, or test result that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements;
6) Administration of other investigational agents (unless approved by Gilead Sciences). Participation in any other clinical trial, including observational trials, without prior approval from the sponsor is prohibited while participating in this trial.
7) History or presence of allergy or intolerance to the study drugs or their components;
8) A new AIDS-defining condition (excluding CD4+ T cell count and percentage criteria) diagnosed within the 30 days prior to screening, with the exception of oropharyngeal candidiasis;
9) Have an implanted defibrillator or pacemaker;
10) Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance;
11) A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive carcinoma;
12) Received solid organ or bone marrow transplant;
13) Significant bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochrondroses), or multiple bone fractures;
14) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1;
15) Systemic chemotherapeutic agents, systemic corticosteroids (except short-term use of prednisone as a steroid burst [ ≤ 1 week of use]), immunosuppressant, or immunomodulating agents;
16) Subjects receiving ongoing therapy with any of the protocol listed medications, including drugs not to be used with EVG, COBI, FTC, TAF: |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the safety and tolerability of E/C/F/TAF FDC in HIV-1 infected adults with ESRD on chronic HD |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) To evaluate the proportion of subjects achieving virologic response (defined as HIV-1 RNA < 50 copies/mL, Snapshot analysis);
2) To evaluate plasma pharmacokinetics (PK) of EVG, COBI, FTC, TAF and TFV in HIV-1 infected patients with ESRD on HD |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Weeks 24, 48 and 96
2) at or between Week 4 or Week 12 |
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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 | 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 | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
France |
Puerto Rico |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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End of the study will occur when the last subject enrolled in the study has completed Week 48 visit followed by a 30-Day Follow-up visit. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |