Clinical Trials Register

Summary
EudraCT Number:	2021-004010-19
Sponsor's Protocol Code Number:	IMEA064
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-08-12
Trial 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

2021-004010-19

A.3

Full title of the trial

Pharmacokinetics of calcineurin & mTOR inhibitors in HIV-1 infected kidney transplant recipients after switch to BIC/FTC/TAF: a pilot study - KINETIK (KIdNEy Transplant bIKtarvy) IMEA 064

A.3.1

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

Pharmacokinetics of antirelease tratment in HIV-1 infected kidney transplant recipients after switch to biktarvy treatment: IMEA 064- KINETIK STUDY

A.3.2

Name or abbreviated title of the trial where available

KINETIK

A.4.1

Sponsor's protocol code number

IMEA064

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	IMEA-Fondation Léon M'Ba
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	IMEA-fondation Léon M'Ba
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Creteil Hospital- Infectious Desease
B.5.2	Functional name of contact point	GALLIEN
B.5.3	Address:
B.5.3.1	Street Address	51 avenue du Maréchal de lattre de Tassigny
B.5.3.2	Town/ city	CRETEIL
B.5.3.3	Post code	94000
B.5.3.4	Country	France
B.5.4	Telephone number	Franc14981443333
B.5.5	Fax number	Franc14981246933
B.5.6	E-mail	sebastien.gallien@aphp.fr

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	EU/1/18/1289/001
D.2.1.2	Country which granted the Marketing Authorisation	Ireland
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	TAF/FTC/BIC
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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

• HIV-1 infected patients > 18 years
• Antiretroviral treatment switch to BIC/FTC/TAF decided in standard care by ID physician
• Kidney transplant recipient ≥ 3 months
• Receiving calcineurin and/or mTOR inhibitors without change in doses ≥ 4 weeks
• Plasma HIV RNA ≤ 50 cpml ≥ 6 months (1 blip permitted 200cp/ml)
• eGFR (CKD-EPI) ≥ 30 ml/mn/1.73m2
• Written consent
• GSS to BIC/FTC/TAF ≥ 2
• Active contraception in potential child-bearing women

E.1.1.1

Medical condition in easily understood language

• HIV-1 infected patients
• Antiretroviral treatment switch to BIC/FTC/TAF
• Kidney transplant recipient
• Receiving calcineurin and/or mTOR inhibitors
• Written consent

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Change in calcineurin & mTOR inhibitors’ blood concentrations from BL to W2 after switch to B/F/TAF (ciclosporine, tacrolimus, everolimus)

E.2.2

Secondary objectives of the trial

• Proportion in calcineurin & mTOR inhibitors’ dose changes from BL to W2 after switch to B/F/TAF
• Changes in plasma levels of calcineurin & mTOR inhibitors
• B/F/TAF plasma levels
• Change in mGFR (iohexol clearance)
• Change in bone mineral density and bone markers
• Incidence of proximal tubulopathy at W48
• Change in eGFR evaluated with plasma or serum Cystatin C
• graft Survival defined as the necessity to return to dialysis, or death
• Change in plasma metabolome from BL to W48

• Incidence of Grade ≥3 adverse events up to Week 48
• Incidence of specific calcineurin inhibitors histological renal damage (if graft biopsy performed for standard care)
• Antiretroviral therapy changes during the follow-up through W48
• Calcineurin & mTOR inhibitors’ drug dose changes from BL to W48
• Immuno-virological efficacy
• Adherence, HIV Treatment Satisfaction (Satisfactory Questionnaire) up to Week 48

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• HIV-1 infected patients > 18 years
• Kidney transplant recipient ≥ 3 months
• Receiving calcineurin and/or mTOR inhibitors without change in doses ≥ 4 weeks
• Plasma HIV RNA ≤ 50 cpml ≥ 6 months (1 blip permitted <200cp/ml)
• eGFR (CKD-EPI) ≥ 30 ml/mn/1.73m2
• Written consent
• GSS to BIC/FTC/TAF = 3
• stable antiretroviral regimen for at least 3 months
• no history of treatment failure
• Active contraception in potential child-bearing women

E.4

Principal exclusion criteria

• Allergy or intolerance to one of the following drug or to any of excipients: FTC, TDF, INSTI
• Current ART containing TAF
• HIV-2 or HIV-1/HIV-2 co-infection
• Patients with severe hepatic impairment (Child-Pugh Class C)
• Patient without health coverage
• Pregnancy and breast-feeding

E.5 End points

E.5.1

Primary end point(s)

Change in calcineurin & mTOR inhibitors’ blood concentrations from BL to W2 after switch to BIKTARVY

E.5.1.1

Timepoint(s) of evaluation of this end point

WEEK 2

E.5.2

Secondary end point(s)

• Proportion in calcineurin & mTOR inhibitors’ dose changes from BL to W2 after switch to B/F/TAF
PK:
• Changes in plasma levels of calcineurin & mTOR inhibitors from baseline to week 2, 12, 24 and 48
• B/F/TAF plasma levels at week 4
Safety
• Change in mGFR (iohexol clearance) from BL to W48
• Change in bone mineral density and bone markers from BL to W48
• Incidence of proximal tubulopathy at W48 (hypouricemia, hypophosphatemia, low molecular weight proteinuria, orthoglycemic glycosuria,
• Change in eGFR evaluated with plasma or serum Cystatin C
• graft Survival defined as the necessity to return to dialysis, or death
• Change in plasma metabolome from BL to W48

• Incidence of Grade ≥3 adverse events up to Week 48
• Incidence of specific calcineurin inhibitors histological renal damage (if graft biopsy performed for standard care)
• Antiretroviral therapy changes during the follow-up through W48
• Calcineurin & mTOR inhibitors’ drug dose changes from BL to W48
• Immuno-virological efficacy:
• Proportion of patients with plasma HIV RNA ≤ 50 cpml at W48
• Change from baseline to W48 of plasma HIV RNA, CD4 cell count, ratio CD4/CD8
• Change in GSS* after switch to B/F/TAF (intervention arm)
• proportion of participants with virological failure defined as two consecutive HIV RNA VL>50 copies/mL or a HIV RNA >50 copies/mL followed by a study treatment discontinuation”
• Genotypic Susceptibility Score (GSS) to B/F/TAF will be calculated as the sum of active (=1), partially active (=0.5) and inactive (=0) drugs according to drug susceptibility using the latest ANRS HIV-1 drug-resistance algorithm from all the resistance genotyping tests available for each patient
• Adherence, HIV Treatment Satisfaction (Satisfactory Questionnaire) up to Week 48

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline, week2, week 12,week 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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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.8.3

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

last visit of the last subject

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

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

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception