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 | 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 efficacy of a fixed dose combination (FDC) containing GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) versus dolutegravir (DTG) + a FDC containing emtricitabine/tenofovir alafenamide (F/TAF) in HIV-1 infected, antiretroviral treatment-naïve adult subjects as determined by the achievement of HIV-1 RNA <50 copies/mL at Week 48 |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy, safety and tolerability of the two treatment groups through Weeks 48, 96 and 144
To evaluate the long term efficacy and safety of FDC GS-9883/F/TAF through open-label (OL) Weeks 48 and 96 |
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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 |
Optional Pharmacokinetic (PK) Substudy: A PK substudy will be performed at the Week 4 or 8 visit in a subset of subjects (approximately n=30 evaluable) at selected study sites. The substudy will include intensive PK profiling in plasma.
Optional Peripheral Blood Mononuclear cell (PBMC) Substudy: A PBMC substudy will be performed at Day 1 and Weeks 36, 84 and 132 in a subset of subjects (target n=50) at select study sites. The substudy will assess HIV-1, PBMC function for HIV disease progression and how the immune system functions in the presence of HIV.
Optional pharmacogenomic substudy- For subjects who agree to participate and provide their additional specific consent, three blood samples will be obtained for the extraction of DNA for genomic testing and for potential genotyping to identify polymorphisms of drug metabolism enzymes including Uridine 5'-diphospho-glucuronosyltransferase(UGT1A1) and additional biomarker testing suchas such as human leukocyte antigen (HLA). These samples will becollected at Day 1. |
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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 or older
3. Antiretroviral treatment naïve (≤ 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection) except the use for PrEP (pre-exposure prophylaxis) or PEP (post-exposure prophylaxis), up to one month prior to screening
4. Plasma HIV-1 RNA levels ≥ 500 copies/mL at screening
5. Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
6. Adequate renal function
7. Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)
8. Total bilirubin ≤ 1.5 mg/dL (≤ 26 umol/L), or normal direct bilirubin
9. Adequate hematologic function (absolute neutrophil count ≥ 750/mm3 (≥ 0.75 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. Females of childbearing potential must agree to utilize protocol recommended highly effective contraceptive methods or be non-heterosexually active or practice sexual abstinence from screening, throughout the duration of the study period, and for 30 days following the last dose of study drug.
a) Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least 3 months prior to study drug dosing.
12. Male subjects who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception throughout the study period and for 90 days following the last dose of study drug.
13. Male subjects must agree to refrain from sperm donation from first study drug dose until at least 90 days following the last study drug dose
14. Life expectancy ≥ 1 year
15. Screening genotype report must show sensitivity to FTC and TFV |
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E.4 | Principal exclusion criteria |
1. An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening
2. Subjects experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding)
3. Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
4. Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
5. A history of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 and are not anticipated to require systemic therapy during the study
6. Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1
7. Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
8. 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 the dosing requirements
9. Any known allergies to the excipients of GS-9883/F/TAF FDC or DTG + F/TAF FDC tablets
10. Females who are pregnant (as confirmed by positive serum pregnancy test)
11. Females who are breastfeeding
12. Subjects receiving ongoing therapy with any of the following medications in the table in the Protocol, including drugs not to be used with FTC, TAF, GS-9883 and DTG
13. Acute hepatitis in the 30 days prior to study entry
14. Screening HBV DNA with HBV viral load > 9 log IU/mL, if determined to be HBV infected
15. Active tuberculosis infection |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm. |
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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) |
- The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Week 96 and 144 as defined by the US FDA-defined snapshot algorithm
- The proportion of subjects who achieve HIV-1 RNA < 20 copies/mL at Weeks 48, 96 and 144 as defined by the US FDA-defined snapshot algorithm
- The change from baseline in log10 HIV-1 RNA and CD4+ cell count at Weeks 48, 96 and 144 the proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 48 OL and 96 OL as defined by Missing = Excluded and Missing = Failure algorithm
- The change from baseline in CD4+ cell count at Weeks 48 OL and 96 OL |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 48, 96 and 144 + Weeks 48 and 96 OL |
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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 | Yes |
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 | 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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Australia |
Belgium |
Canada |
France |
Germany |
Italy |
Puerto Rico |
Spain |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 8 |