E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus (HIV-1) Infection |
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E.1.1.1 | Medical condition in easily understood language |
Human Immunodeficiency Virus (HIV-1) Infection |
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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 | 19.0 |
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 of E/C/F/TAF relative to unchanged current antiretroviral therapy (ART) by assessing spine and hip bone mineral density (BMD) measured at Week 48 in virologically-suppressed, HIV-1 infected subjects aged ≥ 60 years |
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E.2.2 | Secondary objectives of the trial |
- To evaluate spine and hip BMD at Week 24 - To evaluate maintenance of HIV-1 RNA suppression < 50 copies/mL between regimens at Weeks 24 and 48 - To evaluate the safety and tolerability of the two treatment groups through Week 48 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures 2) Age ≥ 60 years 3) Currently receiving a TDF and FTC or 3TC-containing 'backbone' (maximum 2 NRTIs) regimen plus a third agent for ≥ 6 consecutive months prior to screening visit. For subjects with 3 or more ART regimens, a regimen history must be provided for approval by the Sponsor. 4) Documented plasma HIV-1 RNA levels < 50 copies/mL for ≥ 6 months preceding the screening visit 5) Plasma HIV-1 RNA level < 50 copies/mL at screening visit 6) Adequate renal function: Estimated glomerular filtration rate ≥ 30 mL/min according to the Cockcroft-Gault formula (eGFRCG) and are on ARVs that are appropriately dose adjusted for renal function per package insert 7) All documented historical plasma genotype(s) must not show resistance to TDF or FTC, including, but not limited to the presence of reverse transcriptase resistance mutations K65R, K70E, M184V/I or thymidine analog-associated mutations (TAMs) that include M41L, L210W, D67N, K70R, T215Y/F, K219Q/E/N/R. If historical plasma genotype prior to first ART is not available or subject has 3 or more ART regimens, subject will have proviral genotype analysis prior to Day 1 to confirm absence of archived resistance to TDF or FTC. 8) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant) 9) Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN) 10) Total bilirubin ≤ 1.5 mg/dL and normal direct bilirubin (subjects with documented Gilbert’s syndrome or with atazanavir-associated hyperbilirubinemia may have total bilirubin up to 5 × ULN as long as direct bilirubin is normal) 11) Adequate hematologic function - Absolute neutrophil count ≥ 1,000/mm3 - Platelets ≥ 50,000/mm3 - Hemoglobin ≥ 8.5 g/dL 12) Study performed DXA scan and T-score received prior to Day 1 13) Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence, and agree to refrain from sperm donation from first dose throughout the study period and for 30 days following the last dose of study drug. |
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E.4 | Principal exclusion criteria |
1) Previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) (for any length of time) if the current regimen contains a PI/r 2) Subjects will have no evidence of previous virologic failure on a PI/r or INSTI-based regimen (with or without resistance to either class of ARV). 3) A new AIDS-defining condition diagnosed within the 30 days prior to screening (except CD4+ cell count and/or percentage criteria) 4) Hepatitis C virus that would require therapy during the study 5) Subjects with clinical evidence of decompensated cirrhosis (ascites, encephalopathy, variceal bleeding) 6) Women of childbearing potential 7) Subjects receiving ongoing treatment for bone disease (eg, osteoporosis), including bisphosphonates, denosumab, and strontium ranelate 8) Have an implanted defibrillator or pacemaker 9) Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance 10) 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 cutaneous squamous carcinoma. Subjects with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 visit and must not be anticipated to require systemic therapy during the study 11) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Visit 12) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements 13) Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial 14) Known hypersensitivity to the study drug, the metabolites, or formulation excipients 15) Subjects receiving ongoing therapy with any of the medications in Table 4-2 of the protocol, including drugs not to be used due to the potential for interaction with EVG, COBI, FTC, TAF, or 3TC; or subjects with any known allergies to the excipients of E/C/F/TAF FDC tablets. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from Baseline to Week 48 in spine and hip BMD |
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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) Percent change from baseline to Week 24 in spine and hip BMD 2) Proportion of subjects with HIV-1 RNA < 50 copies/mL at Weeks 24 and 48 as defined by the Food and Drug Administration (FDA) snapshot algorithm 3) Change from baseline in CD4+ cell count at Weeks 24 and 48 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Week 24 2) & 3) Weeks 24 and 48 |
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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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |