Clinical Trials Register

Summary
EudraCT Number:	2013-002780-26
Sponsor's Protocol Code Number:	GS-US-292-0106
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2015-01-27
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2013-002780-26

A.3

Full title of the trial

A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) in HIV-1 Infected
Antiretroviral Treatment-Naive Adolescents and Virologically Suppressed Children.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A clinical study looking at the safety and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single tablet regimen (STR) in HIV-1 infected adolescents who have never previously been treated and in children who are currently receiving treatment.

A.4.1

Sponsor's protocol code number

GS-US-292-0106

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01854775

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/019/2015

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Gilead Sciences, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Gilead Sciences, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Gilead Sciences, Inc.
B.5.2	Functional name of contact point	Clinical Trials Mailbox
B.5.3	Address:
B.5.3.1	Street Address	Flowers Building, Granta Park
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB21 6GT
B.5.3.4	Country	United Kingdom
B.5.6	E-mail	clinical.trials@gilead.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide
D.3.2	Product code	E/C/F/TAF
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tenofovir alafenamide
D.3.9.1	CAS number	379270-37-8
D.3.9.3	Other descriptive name	TENOFOVIR ALAFENAMIDE
D.3.9.4	EV Substance Code	SUB121761
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COBICISTAT
D.3.9.1	CAS number	1004316-88-4
D.3.9.4	EV Substance Code	SUB33760
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Elvitegravir
D.3.9.1	CAS number	697761-98-1
D.3.9.3	Other descriptive name	ELVITEGRAVIR
D.3.9.4	EV Substance Code	SUB69759
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EMTRICITABINE
D.3.9.1	CAS number	143491-57-0
D.3.9.4	EV Substance Code	SUB01882MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

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	19.1
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

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Cohort 1 - Part A
- To evaluate the steady state pharmacokinetics (PK) for elvitegravir and tenofovir alafenamide and confirm the dose of the E/C/F/TAF single tablet regimen (STR) in HIV-1 infected, antiretroviral (ARV) treatment-naive adolescents.

Cohort 1 - Part B
- To evaluate the safety and tolerability of the E/C/F/TAF STR through Week 24 in HIV-1 infected, ARV treatment-naive adolescents.

Cohort 2 - Part A
- To evaluate the PK of EVG and TAF in virologically suppressed HIV-1 infected children 6 to <12 years of age, weighing at least 25 Kg, administered E/C/F/TAF STR.

Cohort 2 - Part B
- To evaluate the safety and tolerability of E/C/F/TAF STR though Week 24 in HIV-1 infected children 6 to <12 years of age.

E.2.2

Secondary objectives of the trial

- To evaluate the safety and tolerability of the E/C/F/TAF STR through Week 48 in HIV-1 infected, ARV treatment-naive adolescents
- To evaluate the antiviral activity of the E/C/F/TAF STR through Week 48 in HIV-1 infected, ARV treatment-naive adolescents

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 PBMC PK Substudy
PBMC collection will be performed at PBMC PK substudy sites that can perform PBMC processing. PBMC collection will occur at the Week 32 visit. For PK profiling in PBMCs, blood samples will be collected at 0 (≤ 30 mins pre-dose). Details of PBMC collection and processing will be documented in the PK and PBMC Manual.

E.3

Principal inclusion criteria

Cohort 1
• 12 years to < 18 years of age at Baseline
• Weight ≥ 35 kg (77 lbs) at screening
• Plasma HIV-1 RNA levels of >= 1,000 copies/mL at Screening (Roche COBAS TaqMan v2.0)
• Screening genotype report shows sensitivity to EVG, FTC and TFV
• No prior use of any approved or experimental anti-HIV-1 drug for any length of time (other than that given for prevention of mother-to-child transmission)

Cohort 2
• 6 to < 12 years of age at Baseline
• Weight ≥ 25 kg (55 lbs) at Screening
• Plasma HIV-1 RNA: < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of dectection is > 50 copies/mL) for ≥ 180 consecutive days (6 months) prior to Screening on a stable antiretroviral regimen, without documented history of resistance to any component of E/C/F/TAF STR

Both Cohorts
• CD4+ cell count > 100 cells/μL
• Adequate renal function: Estimated glomerular filtration rate ≥ 90 mL/min/1.73m2
• Clinically normal ECG (or if abnormal, determined by the investigator to be not clinically significant)
• Documented screening for active pulmonary tuberculosis per local standard of care within 6 months of a Screening visit.
• Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function (absolute neutrophil count ≥ 500/mm3; platelets ≥ 50,000/mm3; hemoglobin ≥ 8.5 g/dL)
• Negative serum pregnancy test for all female subjects
• Females of childbearing potential must agree 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 investigational medicinal product. Pre-pubertal females (Tanner Stages 1 and 2 are not considered to be of childbearing potential, unless onset of menarche has occurred).
• 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 Baseline.
• Male subjects must agree to utilize highly effective contraception methods during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from Baseline throughout the study period and for 30 days following discontinuation of investigational medicinal product.
• Able to swallow oral tablets
• Must be willing and able to comply with all study requirements
• Life expectancy > 1 year
• Subjects able to give written assent prior to any screening evaluations
• Parent or guardian able to give written informed consent prior to any screening evaluations and willing to comply with study requirements

E.4

Principal exclusion criteria

• A new AIDS-defining condition diagnosed within the 30 days prior to Screening
• Positive Hepatitis C antibody
• Positive Hepatitis B surface antigen or other evidence of active HBV infection.
• Prior treatment with any approved or investigational or experimental anti HIV-1 drug for any length of time (other than that given for prevention of mother-to-child transmission)
• Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the Screening visit.
• Anticipated to require rifamycin treatment for mycobacterial infection while participating
in the study. Note: prophylactic INH therapy for latent TB treatment is allowed.
• Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
• Pregnant or lactating subjects
• Have an implanted defibrillator or pacemaker
• Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol. This would include uncontrolled renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous,
gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment within 30 days prior to the study dosing.
• Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance.
• Have history of significant drug sensitivity or drug allergy.
• Known hypersensitivity to the study drugs, the metabolites or formulation excipients
• Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study Screening or expected to receive these agents during the study (e.g., immunoglobulins, and other immune- or cytokine-based therapies).
• 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 and must not be anticipated to require systemic therapy during the study.
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline.
• Have previously participated in an investigational trial involving administration of any investigational agent within 30 days prior to the study dosing.
• Participation in any other clinical trial (including observational trials) without prior approval from sponsor is prohibited while participating in this trial.
• Subjects receiving ongoing therapy with any of the medications specified in protocol section 4.3, including drugs not to be used with EVG, COBI, FTC, TDF and TAF (For FTC refer to the individual agents Prescribing Information; for EVG, COBI, and TAF refer to the E/C/F/TAF STR Investigator Brochure); or subjects with any known allergies to the excipients of E/C/F/TAF STR tablets.

E.5 End points

E.5.1

Primary end point(s)

Cohort 1
In Part A of the protocol the primary endpoints are PK parameter of AUCtau for EVG and AUClast for TAF and in Part B the primary endpoints include incidence of treatment-emergent SAEs and all treatment-emergent adverse events.

Cohort 2
In Part A the primary endpoints include PK parameter of AUCtau for EVG and AUClast for TAF, and in Part B the primary endpoints include incidence of treatment-emergent SAEs and all treatment-emergent adverse events.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 10, Week 24 and Week 48

E.5.2

Secondary end point(s)

Cohort 1 - Part A:
• PK parameters of Ctau, Cmax, apparent CL and apparent Vz for EVG, Cmax, apparent CL and apparent Vz for TAF, AUCtau, Cmax, and Ctau for FTC, TFV and COBI.

Cohort 1 - Part B:
• The percentage of subjects with plasma HIV-1 RNA < 50 copies/mL at Weeks 24 and 48 as defined by the FDA snapshot analysis
• The percentage of subjects with plasma HIV-1 RNA < 400 copies/mL at Weeks 24 and 48 as defined by the FDA snapshot analysis
• The change from baseline in plasma log10 HIV-1 RNA (copies/mL) and in CD4+ cell count (cells/μL) and percentage at Weeks 24 and 48

Cohort 2 - Part A:
• PK parameters of Ctau, Cmax, apparent CL and apparent Vz for EVG, Cmax, apparent CL and apparent Vz for TAF, AUCtau, Cmax, and Ctau for FTC, TFV and COBI.

Cohort 2 - Part B
• The percentage of subjects with plasma HIV-1 RNA < 50 copies/mL at Weeks 24 and 48 as defined by the FDA snapshot analysis
• The percentage of subjects with plasma HIV-1 RNA < 400 copies/mL at Weeks 24 and 48 as defined by the FDA snapshot analysis
• The change from baseline in CD4+ cell count (cells/μL) and percentage at Weeks 24 and 48

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 10, Weeks 24 and Week 48

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Multi-cohort, single-arm study

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

South Africa

Thailand

Uganda

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

100

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

100

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After completion of Wk 48, all subjects receiving the E/C/F/TAF who complete 48 weeks of study treatment will be given the option of an extension phase where Gilead will provide the E/C/F/TAF until: a) subject turns 18 and E/C/F/TAF is commercially available for use in adults in the country the subject is enrolled or b) E/C/F/TAF becomes commercially available for use in adolescents in the country the subject is enrolled or c) Gilead terminates development of the E/C/F/TAF STR in the country.

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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IMP with orphan designation in the indication
Orphan Designation Number:
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