| 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 | 17.0 |
| 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 |
|
| 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 efficacy of switching FTC/TDF to F/TAF versus maintaining FTC/TDF in HIV-1 positive subjects who are virologically suppressed on regimens containing FTC/TDF as determined by the proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48. |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the bone safety of two regimens as determined by the percentage change from baseline in hip and spine bone mineral density at Week 48
- To evaluate the efficacy, safety, and tolerability of two regimens through Week 48 and Week 96
- To evaluate the pharmacokinetics of TAF and tenofovir |
|
| 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 ≥ 18 years
3. Currently receiving antiretroviral regimen containing FTC/TDF in combination with one
third agent for ≥ 6 consecutive months prior to Screening. Refer to Table 3 in the protocol for allowed third agents of the pre-existing regimen.
4. Plasma HIV-1 RNA levels < 50 copies/mL for at ≥ 6 months preceding the screening visit (measured at least twice using the same assay) and not experienced two consecutive HIV-1 RNA above detectable levels after achieving a confirmed (two consecutive) HIV-1 RNA below detectable levels on the current regimen in the past year.
a. To determine virologic suppression in the preceding 6 months prior to screening, lower limit of quantification (LLOQ) by the local HIV-1 RNA assay may its LLOQ is greater than 50 copies/mL (e.g. LLOQ of 75 copies/mL).
5. Plasma HIV-1 RNA levels < 50 copies/mL at Screening Visit.
6. Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
7. Estimated GFR ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
8. Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
9. Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (subjects with documented Gilbert’s syndrome or with Atazanavir-associated hyperbilirubinemia may have total bilirubin up to 5 x ULN)
10. Adequate hematologic function (absolute ≥ 50,000/mm3; hemoglobin ≥ 8.5 g/dL)
11. Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
12. 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).
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, or
c. Of childbearing potential and agrees to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following discontinuation of study drugs.
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.
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 from first dose throughout the study period and for 30 days following the last study drug dose.
a. 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. A new AIDS-defining condition diagnosed within the 30 days prior to screening (except CD4 cell count and/or percentage criteria)
2. Hepatitis C virus (HCV) antibody positive and HCV RNA detectable
3. Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
4. Subjects receiving ongoing treatment with bisphosphonate to treat bone disease (e.g. osteoporosis)
5. Females who are breastfeeding
6. Positive serum pregnancy test
7. Have an implanted defibrillator or pacemaker
8. Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
9. 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
10. Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Visit
11. 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
12. Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial
13. Subjects receiving ongoing therapy with any of the medications specified on protocol p.36, including drugs not to be used with FTC, TAF, TDF or other antiretroviral third agents (refer to the individual agents Prescribing Information); or subjects with any known allergies to the study drugs. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the FDA snapshot analysis. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The key secondary endpoints include:
- The percent change from baseline in hip BMD at Week 48
-The percent change from baseline in spine BMD at Week 48
Other secondary endpoints include:
- The proportion of subjects with HIV-1 RNA < 50 copies/mL at Weeks 96 as defined by the FDA snapshot analysis
- The proportion of subjects with HIV-1 RNA < 20 copies/mL at Weeks 48 and 96 as defined by the FDA snapshot analysis
- The change from baseline in CD4+ cell count at Weeks 48 and 96
- The percent change from baseline in hip and spine BMD at Week 96 |
|
| 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 | 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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 | 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 |
| Italy |
| Puerto Rico |
| 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 | 7 |
| 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 | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
