Clinical Trials Register

Summary
EudraCT Number:	2021-001073-23
Sponsor's Protocol Code Number:	GS-US-380-5310
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2021-03-08
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2021-001073-23

A.3

Full title of the trial

A Phase 1b, Open-label study to Evaluate the PK, Safety and Efficacy of B/F/TAF in HIV-1 infected, Virologically Suppressed, Pregnant Women in their Second and Third Trimesters

A.3.1

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

The purpose of this study is to evaluate the steady state pharmacokinetics and confirm the dose of BIC/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed dose combination (FDC) in HIV-1 infected, virologically suppressed pregnant women in their second and third trimesters.

A.4.1

Sponsor's protocol code number

GS-US-380-5310

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	Yes
D.2.1.1.1	Trade name	Biktarvy
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences Ireland UC
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Biktarvy
D.3.2	Product code	B/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	BICTEGRAVIR
D.3.9.1	CAS number	1807988-02-8
D.3.9.2	Current sponsor code	GS-9883
D.3.9.3	Other descriptive name	GS-9883
D.3.9.4	EV Substance Code	SUB182699
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	50
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.3.9.2	Current sponsor code	FTC; F
D.3.9.3	Other descriptive name	EMTRICITABINE
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.3.8 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.3.9.2	Current sponsor code	TAF
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	25
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) Infections

E.1.1.1

Medical condition in easily understood language

HIV-1 Infection

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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

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 steady state pharmacokinetics (PK) of bictegravir (BIC) and confirm the dose of BIC/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed dose combination (FDC) in the second and third trimesters of pregnancy

E.2.2

Secondary objectives of the trial

• To evaluate the steady state PK of emtricitabine (FTC) and TAF in the second and third trimesters of pregnancy
• To evaluate maintenance of HIV-1 virologic suppression in pregnant women receiving the B/F/TAF FDC during the second and/or third trimesters

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participants 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 study procedures
2) Female participants of age ≥ 18 to < 40 years with singleton pregnancy, at least 12 weeks but not more than 31 weeks pregnant at the time of screening
3) Agree not to breastfeed for the duration of the study
4) Currently on a stable antiretroviral regimen for ≥ 6 months preceding the screening visit
5) Documented plasma HIV-1 RNA levels of < 50 copies/mL for ≥ 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at the Screening Visit
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)
6) Have no documented or suspected resistance to FTC, TFV, or INSTIs including, but not limited to, the reverse transcriptase resistance mutations K65R or M184V/I.
a) Historic genotype reports will be collected if available
7) Have a normal ultrasound, completed locally prior to the Day 1 visit, with no evidence of any fetal malformation or structural abnormality affecting either fetus or placenta
8) Normal maternal alfa-fetoprotein level at the Screening Visit
9) Estimated glomerular filtration rate (eGFR) ≥ 90 mL/min according to the Cockcroft-Gault (C-G) formula {Cockcroft 1976}:
(140 – age in years) X (wt in kg) / 72 X (serum creatinine in mg/dL) X 0.85 = CLcr (mL/min)
(140 – age in years) x (wt in kg) x 0.85 / 72 x (serum creatinine in umol/L) x 0.6786 = CLcr (mL/sec)
10) Normal ECG (or if abnormal, determined by the investigator not to be clinically significant)
11) Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)
12) Total bilirubin ≤ 1.5 mg/dL (≤ 26 umol/L), or normal direct bilirubin
13) Adequate hematologic function (absolute neutrophil count ≥ 750/mm3 (≥ 0.75 GI/L); platelets ≥ 50,000/mm3 (≥ 50 GI/L); hemoglobin ≥ 9.5 g/dL (≥ 95 g/L))
14) Serum amylase ≤ 5 × ULN (participants with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
15) Participants of childbearing potential must agree to utilize protocol recommended highly effective contraceptive methods or be non-heterosexually active or practice sexual abstinence (as defined in Appendix 6) during the post-partum period of the study, and for 7 days following the last dose of study drug.

E.4

Principal exclusion criteria

Participants who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Have chronic hepatitis B virus (HBV) as determined by either:
a) Positive HBV surface antigen (HBsAg) at the Screening Visit
b) Negative HBV surface antigen, negative HBV surface antibody, positive HBV core antibody and quantifiable HBV DNA (HBV DNA ≥ 20 IU/mL) at
the Screening Visit
2) Have active hepatitis C virus (HCV) infection
a) Positive anti-HCV antibody and negative HCV polymerase chain reaction (PCR) results are acceptable
3) An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening (refer to Appendix 5)
4) Participants experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding)
5) 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 (e.g, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
6) Malignancy within 5 years of screening other than cutaneous Kaposi’s sarcoma, completely resected non-melanoma skin cancer (basal cell carcinoma or non-invasive cutaneous squamous carcinoma), or completely resected carcinoma in-situ of the cervix (CIN 3) or anus (AIN 3). A prior malignancy treated with curative therapy and for which there has been no evidence of disease for at least five years prior to screening is allowed.
7) Current alcohol or substance use judged by the Investigator to potentially interfere with participant study compliance
8) Active, serious infections (other than HIV-1 infection) requiring antibiotic or antifungal therapy within 30 days prior to Day 1
9) Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
10) Any other clinical condition, including pregnancy complications such as gestational diabetes or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with the dosing requirements
11) Active tuberculosis infection
12) Known hypersensitivity to B/F/TAF, their metabolites, or formulation excipient.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the PK parameter AUCtau of BIC during the second and/or third trimesters through post-partum.

E.5.1.1

Timepoint(s) of evaluation of this end point

Intensive PK (iPK) visits during second and/or third trimesters through post-partum with sample collection timepoints as follows: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

E.5.2

Secondary end point(s)

• The PK parameter AUCtau for FTC and TAF, and PK parameters AUClast, Cmax, Ctau, Clast, Tmax, T1/2, CL/F, Vz/F and λz for BIC, FTC and TAF, as applicable
• The proportion of participants with plasma HIV-1 RNA < 50 copies/mL at the time of delivery by missing = excluded approach.

E.5.2.1

Timepoint(s) of evaluation of this end point

- Intensive PK (iPK) visits during second and/or third trimesters through post-partum with sample collection timepoints as follows: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
- At the delivery visit

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

Yes

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Phase 1b

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

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

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

Dominican Republic

Puerto Rico

Thailand

United States

E.8.7

Trial has a data monitoring committee

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

The end of the study will be the last subject’s last observation (or visit).

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

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)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

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

F.3.3.3

Pregnant women

Yes

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

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

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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