| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Immunodeficiency Virus (HIV-1) Infection |
|
| E.1.1.1 | Medical condition in easily understood language |
| Human Immunodeficiency Virus (HIV-1) Infection |
|
| 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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10068341 |
| E.1.2 | Term | HIV-1 infection |
| E.1.2 | System Organ Class | 100000020174 |
|
| 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 non-inferiority of switching to the FTC/RPV/TAF FDC as compared to continuing FTC/RPV/TDF FDC in
virologically suppressed HIV-1 infected subjects as determined by maintaining HIV-1 RNA < 50 copies/mL at Week 48 (FDA Snapshot Algorithm) |
|
| E.2.2 | Secondary objectives of the trial |
To determine the safety of the two treatment arms as determined by the percent change from baseline in hip and spine bone mineral density as assessed by dual energy X-ray absorptiometry (DXA) at Week 48 and 96 in a subset of subjects
To evaluate the safety and tolerability of the two treatment arms through Week 48
To evaluate the efficacy, safety and tolerability of the two treatment arms though Week 96 |
|
| 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 |
| The substudy is detailed within the main protocol. A subset of subjects, who provide separate informed consent, will have DXA scans performed prior to study drug administration at Baseline/Day 1, and then every 24 weeks throughout the study and at the Early Study Drug Discontinuation Visit, if >12 weeks since last scan. Scans will cover the hip and spine to measure changes in bone mineral density. Blood and urine for bone and renal safety evaluations will be collected at Baseline/Day 1, every 24 weeks, Unblinding and ESDD (if applicable). |
|
| 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 ≥ 18 years
3. Currently receiving FTC/RPV/TDF FDC for ≥ 6 consecutive months preceding the Screening visit
4. Documented plasma HIV-1 RNA levels < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is >50 copies/mL) for ≥ 6 months preceding the Screening visit. After reaching HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA ≥ 50 copies/mL followed by resuppression are allowed
5. Have no documented resistance to any of the study agents at any time in the past, including but not limited to the reverse transcriptase resistance mutations K65R, K70E, K101E/P, E138A/G/K/R/Q, V179L, Y181C/I/V, M184V/I, Y188L, H221Y, F227C, M230I/L, the combination of K103N+L100I , or 3 or more thymidine analog associated mutations (TAMs) that include M41L or L210W (TAMs are M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R)
6. HIV-1 RNA < 50 copies/mL at the Screening visit
7. Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
8. Total bilirubin ≤ 1.5 mg/dL (≤ 26μmol/L), or normal direct bilirubin
9. Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm3 (1.00 GI/L);
platelets ≥50,000/mm3 (50 GI/L); hemoglobin ≥ 8.5 g/dL (85 g/L))
10. Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if
serum lipase is ≤ 5 × ULN)
11. Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
12. Adequate renal function: Estimated glomerular filtration rate 50 mL/min (1.17 mL/sec) according to the Cockcroft-Gault formula
13. A female subject is eligible to enter the study if it is confirmed that she is:
a) Not pregnant or nursing
b) Of non-childbearing 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), or
c) Of childbearing potential and agrees to utilize highly effective protocol-specified contraceptive method or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following the last study drug dose
d) Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
14. Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the
last study drug dose
15. Male subjects must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose |
|
| E.4 | Principal exclusion criteria |
1. Hepatitis B surface antigen (HBsAg) positive
2. Hepatitis C antibody positive with detectable HCV RNA (subjects who have HCV antibody but no detectable HCV RNA are eligible to enroll)
3. Subjects experiencing or with a medical history of decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
4. Females who are breastfeeding
5. Positive serum pregnancy test
6. Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
7. 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 Baseline/Day 1 and must not be
anticipated to require systemic therapy during the study
8. Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline/Day 1
9. 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
10. Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial
11. Subjects receiving ongoing therapy with any of the specified medications in the protocol, including drugs not to be used with FTC, RPV and/or TAF (refer to the individual agents Prescribing Information); or subjects with any known allergies to the excipients of
FTC/RPV/TAF |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary analysis will consist of a non-inferiority evaluation of switching to FTC/RPV/TAF FDC versus continuing FTC/RPV/TDF
FDC, with respect to the proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 after the start of treatment in this study
(as defined by the FDA snapshot algorithm). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The proportion of subjects with HIV-1 RNA ≥ 50 copies/mL at Weeks 48 and 96, and the proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 96, as defined by the US FDA-defined snapshot algorithm.
The comparison of FTC/RPV/TAF versus FTC/RPV/TDF, with respect to the percent change from baseline in hip and spine bone mineral density (BMD) in DXA substudy will be conducted using Analysis of Variance (ANOVA) model, including treatment group as a fixed effect in the model.
The AE and clinical laboratory data will be summarized using descriptive statistics. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Biomarker samples for optional future research: separate, specific signature will be required to document a subject's agreement to provide additional samples or to allow the use of the remainder of their already collected samples for optional future research, once approved by local authorities as applicable according to specific local regulations |
|
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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 | Yes |
| 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 | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 49 |
| 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 |
| Belgium |
| Canada |
| France |
| Germany |
| Italy |
| Netherlands |
| Spain |
| Sweden |
| Switzerland |
| United Kingdom |
| United States |
|
| 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
|
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 10 |
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