Clinical Trials Register

Summary
EudraCT Number:	2015-002713-30
Sponsor's Protocol Code Number:	GS-US-292-1825
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-01-08
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
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2015-002713-30

A.3

Full title of the trial

A Phase 3b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Subjects on Chronic Hemodialysis

A.3.1

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

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Subjects on Chronic Hemodialysis

A.4.1

Sponsor's protocol code number

GS-US-292-1825

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

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 International Ltd.
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	Abington, Cambridge
B.5.3.3	Post code	CB21 6GT
B.5.3.4	Country	United Kingdom
B.5.5	Fax number	+441223897284
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 in Subjects on Chronic Hemodialysis

E.1.1.1

Medical condition in easily understood language

Human Immunodeficiency Virus (HIV-1) Infection in Subjects on Chronic Hemodialysis

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	18.1
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

To evaluate the safety and tolerability of the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF; E/C/F/TAF) fixed dose combination (FDC) in HIV-1 infected adults with end stage renal disease (ESRD) on chronic hemodialysis (HD) at Week 48

E.2.2

Secondary objectives of the trial

- To evaluate the proportion of subjects achieving virologic response (defined as HIV-1 RNA < 50 copies/mL, Snapshot analysis) at Weeks 24 and 48
- To evaluate plasma pharmacokinetics (PK) of EVG, COBI, FTC, TAF and TFV in HIV-1 infected patients with ESRD on HD

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

Pharmacokinetic (PK) Sub-study : All subjects who provide consent will be eligible to participate in the PK sub-study (target n=15). For the PK sub-study, intense blood sampling will be conducted at or between Week 2 or Week 4 study visits, on a day prior to the day of hemodialysis and when the subject has administered three doses of E/C/F/TAF between two hemodialysis sessions. The PK of EVG, COBI, FTC, TAF and TFV will be evaluated. Study drug administration will be observed in-clinic at the sub-study visit.

E.3

Principal inclusion criteria

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:
1) The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of screening procedures;
2) Age ≥ 18 years;
3) Currently receiving a stable ARV regimen for ≥ 6 consecutive months prior to screening;
4) Documented plasma HIV-1 RNA concentrations < 50 copies/mL for at least 6 months preceding the screening visit measured at least twice using the same assay) and have HIV-1 RNA < 50 copies/mL at screening; a) In the preceding 6 months prior to screening, one episode of “blip” (HIV-1 RNA ≥ 50 copies/mL and < 400 copies/mL) is acceptable, only if HIV-1 RNA is < 50 copies/mL immediately before and after the blip. b) To determine virologic suppression in the preceding 6 months prior to screening, the lower limit of quantification (LLOQ) by the local HIV-1 RNA assay may be used, only if its LLOQ is greater than 50 copies/mL (e.g. LLOQ of 75 copies/mL);
5 )No documented history of HIV-1 resistance to EVG, FTC, 3TC or TFV and no history of switching off EVG, FTC, 3TC or TFV due to concern for resistance;
6) CD4+ T cell count of ≥ 200 cells/μL;
7) ESRD with eGFR < 15 mL/min by Cockcroft-Gault formula for creatinine clearance;
8) On chronic HD for ≥ 6 months prior to screening;
9) Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN);
10) Chronic Hepatitis C (HCV) infection allowed if liver function is stable (see above for criteria);
11) Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm3; platelets ≥ 50,000/mm3; hemoglobin ≥ 8.5 g/dL);
12) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN);
13) A female subject is eligible to enter the study if it is confirmed that she is: a) Not pregnant confirmed by a negative serum pregnancy test (unless permanently sterile or greater than two years post-menopausal); b) Of non-child bearing 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. c) Of childbearing potential and agrees to utilize the protocol specified method of contraception or be non-heterosexually active or practice abstinence from screening throughout the duration of the study treatment and for 30 days following study drug discontinuation; d) Female subjects who utilize hormonal contraception as one of the birth control methods must have used the same method for at least three months prior to the study dosing.
14) Male subjects must agree to use protocol specified method(s) of contraception from screening throughout the duration of study treatment and for 30 days following discontinuation of study drugs.
15) Male subjects must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.
16) Lactating females must agree to discontinue nursing before the study drug is administered.

E.4

Principal exclusion criteria

Subjects who meet any of the following exclusion criteria are not to be enrolled in this study :
1) Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.);
2) Hepatitis B surface antigen (HBsAg) positive;
3) Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening;
4) Treatment with radiation, cytotoxic chemotherapeutic agents, or any immunomodulator within 30 days of screening;
5) Any other clinical history, condition, or test result that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements;
6) Administration of other investigational agents (unless approved by Gilead Sciences). Participation in any other clinical trial, including observational trials, without prior approval from the sponsor is prohibited while participating in this trial.
7) History or presence of allergy or intolerance to the study drugs or their components;
8) A new AIDS-defining condition (excluding CD4+ T cell count and percentage criteria) diagnosed within the 30 days prior to screening, with the exception of oropharyngeal candidiasis;
9) Have an implanted defibrillator or pacemaker;
10) Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance;
11) 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 carcinoma;
12) Received solid organ or bone marrow transplant;
13) Significant bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochrondroses), or multiple bone fractures;
14) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1;
15) Systemic chemotherapeutic agents, systemic corticosteroids (except short-term use of prednisone as a steroid burst [ ≤ 1 week of use]), immunosuppressant, or immunomodulating agents;
16) Subjects receiving ongoing therapy with any of the protocol listed medications, including drugs not to be used with EVG, COBI, FTC, TAF:

E.5 End points

E.5.1

Primary end point(s)

To evaluate the safety and tolerability of E/C/F/TAF FDC in HIV-1 infected adults with ESRD on chronic HD

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 48

E.5.2

Secondary end point(s)

1) To evaluate the proportion of subjects achieving virologic response (defined as HIV-1 RNA < 50 copies/mL, Snapshot analysis);
2) To evaluate plasma pharmacokinetics (PK) of EVG, COBI, FTC, TAF and TFV in HIV-1 infected patients with ESRD on HD

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Weeks 24 and 48
2) at or between Week 4 or Week 8

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)

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

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

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Puerto Rico

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

End of the study will occur when the last subject enrolled in the study has completed Week 48 visit followed by a 30-Day Follow-up visit.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2016-01-08.

Yes

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.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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 a subject has completed/terminated their participation in the study, long-term care for the subject will remain the responsibility of their primary treating physician.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	National Institute for Health Research
G.4.3.4	Network Country	United Kingdom

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-12-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-10-15

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