This study will test an experimental drug called GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) for the treatment of HIV-1 infection. The purpose of this study is to evaluate safety, and to determine whether GS-9883/F/TAF as a fixed dose combination maintains the control of HIV-1 infection effectively compared to treatment with dolutegravir (DTG) (trade name Tivicay) and emtricitabine/tenofovir alafenamide (F/TAF).

• Register: EUCTR
• Last refreshed on: 10 August 2021
• Main ID: EUCTR2015-003988-10-BE
• Date of registration: 01/12/2015
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: This study will test an experimental drug called GS-9883/emtricitabine/tenofovir alafenamide (GS-9883/F/TAF) for the treatment of HIV-1 infection. The purpose of this study is to evaluate safety, and to determine whether GS-9883/F/TAF as a fixed dose combination maintains the control of HIV-1 infection effectively compared to treatment with dolutegravir (DTG) (trade name Tivicay) and emtricitabine/tenofovir alafenamide (F/TAF).
• Scientific title: A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral Treatment-Naïve Adults
• Date of first enrolment: 25/01/2016
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003988-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Italy, Puerto Rico, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

Key inclusion & exclusion criteria

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Human Immunodeficiency Virus (HIV-1) Infection
MedDRA version: 20.1 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Code: GS-9883/F/TAF
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: GS-9883
Current Sponsor code: GS-9883
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: EMTRICITABINE
CAS Number: 143491-57-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: TENOFOVIR ALAFENAMIDE
CAS Number: 379270-37-8
Other descriptive name: TENOFOVIR ALAFENAMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Descovy
Product Code: F/TAF
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: EMTRICITABINE
CAS Number: 143491-57-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: TENOFOVIR ALAFENAMIDE
CAS Number: 379270-37-8
Other descriptive name: TENOFOVIR ALAFENAMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Tivicay
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DOLUTEGRAVIR
Other descriptive name: DOLUTEGRAVIR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

Main Objective: 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

Secondary Objective: 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

Timepoint(s) of evaluation of this end point: Week 48

Secondary Outcome(s)

Secondary end point(s): - The proportion of subjects who achieve HIV-1 RNA < 50 copies/mL at Weeks 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

Timepoint(s) of evaluation of this end point: Weeks 48, 96 and 144 + Weeks 48 and 96 OL

Secondary ID(s)

GS-US-380-1490

2015-003988-10-GB

Source(s) of Monetary Support

Gilead Sciences, Inc.

Ethics review

Status: Approved
Approval date: 25/01/2016
Contact: