A low-intervention prospective-retrospective study to evaluate the pharmacokinetics of elexacaftor/tezacaftor/ivacaftor combination in a Cystic Fibrosis population

2024-518785-28-00 Protocol PKCAFTORs Therapeutic use (Phase IV) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 4 sites · Protocol PKCAFTORs

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Authorised, recruitment pending
Participants planned 50
Countries 1
Sites 4

Cystic Fibrosis

To determine plasma profiles of ELX, TEZ and IVA when administered in combination.

Key facts

Sponsor
IRCCS Istituto Giannina Gaslini
Participant type
Pediatric, Patients
Age range
0-17 years, 18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16], Diseases [C] - Respiratory Tract Diseases [C08]
Decision date (initial)
2025-09-24
Transition trial
No
Low-intervention
Yes
Rare-disease indication
Yes
Vulnerable population
Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacogenetic

To determine plasma profiles of ELX, TEZ and IVA when administered in combination.

Secondary objectives 4

  1. To evaluate the PK of ELX, TEZ and IVA.
  2. Evaluation of the tolerability of ETI treatment.
  3. Evaluation of possible correlations between AEs arising during ETI treatment and PK of ELX, TEZ and IVA.
  4. Evaluation of potential associations between ETI pharmacokinetics and therapeutic response, distinguishing among responders, non-responders, and unresolved responders.

Conditions and MedDRA coding

Cystic Fibrosis

VersionLevelCodeTermSystem organ class
20.0 PT 10011762 Cystic fibrosis 100000004850

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

  1. CF patients with at least one F508del mutation treated with the combination ETI for a time sufficient to reach steady-state (8 days).
  2. Males and females aged ≥6 years.
  3. Informed consent to participate in the study and to process the patient's personal data obtained prior to the collection of any study data.

Exclusion criteria 6

  1. Evidence of inadequate compliance to treatment.
  2. Pregnancy and/or breastfeeding.
  3. Any conditions that may affect the ability to complete informed consent.
  4. Any other severe systemic disorders that may compromise the PK parameters.
  5. Use of any drug capable of moderately/strongly inhibiting or strongly inducing hepatic biotransformation.
  6. Denial of the informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Plasma concentrations of ELX, TEZ and IVA at steady-state (Css).

Secondary endpoints 4

  1. Population pharmacokinetics (popPK) analysis of ELX, TEZ and IVA at steady state.
  2. Harvest of every AE/Adverse Drug Reaction (ADR).
  3. Correlation between PK of ELX, TEZ and IVA and number of AEs
  4. Correlation between PK and ETI efficacy (ppFEV1 and Cl- values at T0) in the 3 groups classifications (responders, non responders and unresolved responders) of ETI

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Kaftrio 37.5 mg/25 mg/50 mg film-coated tablets

PRD9418409 · Product

Active substance
Tezacaftor
Substance synonyms
VX-661, 1-(2,2-DIFLUORO-2H-1,3-BENZODIOXOL-5-YL)-N-{1-[(2R)-2,3-DIHYDROXYPROPYL]-6-FLUORO-2-(1-HYDROXY-2-METHYLPROPAN-2-YL)-1H-INDOL-5-YL}CYCLOPROPANE-1-CARBOXAMIDE, 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-{1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1Hindol-5-yl}cyclopropanecarboxamide
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
225 mg milligram(s)
Max total dose
82125 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
R07AX32 — -
Marketing authorisation
EU/1/20/1468/002
MA holder
VERTEX PHARMACEUTICALS (IRELAND) LIMITED
MA country
EU
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/18/2116
Modified vs. Marketing Authorisation
No

Kaftrio 75 mg/50 mg/100 mg film-coated tablets

PRD8271954 · Product

Active substance
Tezacaftor
Substance synonyms
VX-661, 1-(2,2-DIFLUORO-2H-1,3-BENZODIOXOL-5-YL)-N-{1-[(2R)-2,3-DIHYDROXYPROPYL]-6-FLUORO-2-(1-HYDROXY-2-METHYLPROPAN-2-YL)-1H-INDOL-5-YL}CYCLOPROPANE-1-CARBOXAMIDE, 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-{1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1Hindol-5-yl}cyclopropanecarboxamide
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
450 mg milligram(s)
Max total dose
164250 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
R07AX32 — -
Marketing authorisation
EU/1/20/1468/001
MA holder
VERTEX PHARMACEUTICALS (IRELAND) LIMITED
MA country
EU
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/18/2116
Modified vs. Marketing Authorisation
No

Kalydeco 150 mg film-coated tablets

PRD3203571 · Product

Active substance
Ivacaftor
Substance synonyms
VX-770, N-(2,4-Di-tert-butyl-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
150 mg milligram(s)
Max total dose
54750 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
R07AX02 — -
Marketing authorisation
EU/1/12/782/001
MA holder
VERTEX PHARMACEUTICALS (IRELAND) LIMITED
MA country
EU
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/08/556
Modified vs. Marketing Authorisation
No

Kalydeco 75 mg film-coated tablets

PRD8533015 · Product

Active substance
Ivacaftor
Substance synonyms
VX-770, N-(2,4-Di-tert-butyl-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
75 mg milligram(s)
Max total dose
27375 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
R07AX02 — -
Marketing authorisation
EU/1/12/782/007
MA holder
VERTEX PHARMACEUTICALS (IRELAND) LIMITED
MA country
EU
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/08/556
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

IRCCS Istituto Giannina Gaslini

8 Total trials 4 Recruiting 2 Ended
Academic / Non-commercial
Sponsor organisation
IRCCS Istituto Giannina Gaslini
Address
Via Gerolamo Gaslini 5
City
Genoa
Postcode
16147
Country
Italy

Scientific contact point

Organisation
IRCCS Istituto Giannina Gaslini
Contact name
Giuliana Cangemi

Public contact point

Organisation
IRCCS Istituto Giannina Gaslini
Contact name
Federico Cresta

Locations

1 EU/EEA country · 4 investigational sites

By country

CountryMS statusPlanned subjectsSites
Italy Authorised, recruitment pending 50 4
Rest of world — 0 —

Investigational sites

Italy

4 sites · Authorised, recruitment pending
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
SC Pneumologia e Fibrosi Cistica, Via Francesco Sforza 35, 20122, Milan
IRCCS Istituto Giannina Gaslini
UOC Laboratorio Analisi, Via Gerolamo Gaslini 5, 16147, Genoa
Istituto Di Ricovero E Cura A Carattere Scientifico Materno Infantile Burlo Garofolo
Pneumologia e Fibrosi Cistica, Via Dell' Istria 65/1, 34137, Trieste
Azienda Ospedaliera Universitaria Meyer IRCCS
Centro Regionale Fibrosi Cistica - Toscana, Viale Gaetano Pieraccini 24, 50139, Florence

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-518785-28-00 1.2
Recruitment arrangements (for publication) K1_Recruitment arrangements 2
Subject information and informed consent form (for publication) L1_Letter to general practitioner 1
Subject information and informed consent form (for publication) L1_SIS and ICF 12-17 yr 1.1
Subject information and informed consent form (for publication) L1_SIS and ICF 6-11 yr 1.1
Subject information and informed consent form (for publication) L1_SIS and ICF adult_privacy 1.1
Subject information and informed consent form (for publication) L1_SIS and ICF adults 1.1
Subject information and informed consent form (for publication) L1_SIS and ICF biobank adults 5
Subject information and informed consent form (for publication) L1_SIS and ICF biobank legal guardian 5
Subject information and informed consent form (for publication) L1_SIS and ICF biobank minors 5
Subject information and informed consent form (for publication) L1_SIS and ICF parents 1.1
Subject information and informed consent form (for publication) L1_SIS and ICF parents_privacy 1.1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC Kaftrio 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC Kalydeco 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_ENG_2024-518785-28-00 1.1
Synopsis of the protocol (for publication) D1_Protocol synopsis_ITA_2024-518785-28-00 1.2

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-06-06 Italy Acceptable
2025-09-11
 2025-09-24

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