Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruitment ended
Participants planned
50
Countries
3
Sites
5
Cystic Fibrosis
To evaluate the long-term safety and tolerability of elexacaftor (ELX)/tezacaftor(TEZ)/ivacaftor (IVA)
Key facts
- Sponsor
- Vertex Pharmaceuticals Inc.
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Respiratory Tract Diseases [C08]
- Trial duration
- 8 Jan 2025 → ongoing
- Decision date (initial)
- 2024-10-21
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
To evaluate the long-term safety and tolerability of elexacaftor (ELX)/tezacaftor(TEZ)/ivacaftor (IVA)
Secondary objectives 1
- To evaluate the long-term efficacy and pharmacodynamics (PD) of ELX/TEZ/IVA
Conditions and MedDRA coding
Cystic Fibrosis
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10011762 | Cystic fibrosis | 100000004850 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Subject’s legally appointed and authorized representative will sign and date the informed consent form (ICF).
- As judged by the investigator, the legal representative or guardian must be able to understand protocol requirements, restrictions, and instructions, and the legal representative or guardian should be able to ensure that the subject will comply with and is likely to complete the study as planned.
- Did not withdraw consent from the parent study.
- Meets at least 1 of the following criteria: • Completed study drug treatment in the parent study, or • Had study drug interruption(s) in the parent study but did not permanently discontinue study drug and completed study visits up to the last scheduled visit of the Treatment Period of the parent study.
- Willing to remain on a stable CF treatment regimen (as defined in Section 9.5) through completion of study participation.
Exclusion criteria 6
- History of any illness or any clinical condition that might confound the results of the study or pose an additional risk in administering study drug(s) to the subject. This includes, but is not limited to, the following: • Clinically significant liver cirrhosis with or without portal hypertension • Solid organ or hematological transplantation • Cancer
- History of drug intolerance in the parent study that would pose an additional risk to the subject (e.g., subjects with a history of allergy or hypersensitivity to the study drug).
- Current participation in an investigational drug trial other than the parent study. Participation in a noninterventional study (including observational studies, registry studies, and studies requiring blood collections without administration of study drug) and screening for another Vertex study is permitted.
- History of poor compliance with ELX/TEZ/IVA and/or procedures in the parent study as deemed by the investigator.
- Use of restricted medication, as defined in Table 9-2, unless subject is on a study drug interruption at the time of rollover.
- The subject or close relative of the subject is the investigator or a sub-investigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study at the site.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Safety and tolerability assessments as determined by adverse events (AEs), clinical laboratory values, standard 12-lead ECGs, vital signs, and pulse oximetry
Secondary endpoints 1
- Absolute change in sweat chloride (SwCl)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 14
Kaftrio 60 mg/40 mg/80 mg granules in sachet
PRD10968552 · 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
- ORAL SOLUTION
- Route of administration
- ORAL
- Max daily dose
- 80 mg milligram(s)
- Max total dose
- 80 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Authorised
- ATC code
- R07AX32 — -
- Marketing authorisation
- EU/1/20/1468/003
- MA holder
- VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/18/2116
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Modified strength
Kalydeco 75 mg granules in sachet
PRD3450699 · 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
- GRANULES
- Route of administration
- ORAL
- Max daily dose
- 75 mg milligram(s)
- Max total dose
- 75 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Authorised
- ATC code
- R07AX02 — -
- Marketing authorisation
- EU/1/12/782/004
- 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
- Yes
- Modification description
- Modified strength
PRD5377048 · Product
- Active substance
- Ivacaftor
- Pharmaceutical form
- GRANULES
- Route of administration
- ORAL
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 25 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- VERTEX PHARMACEUTICALS, INCORPORATED
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/08/556
VX-445/VX-661/VX-770 fixed-dose combination granules
PRD8315183 · Product
- Active substance
- Tezacaftor
- Other product name
- VX-445/TEZ/IVA VX-445/Tezacaftor/Ivacaftor Elexacaftor/Tezacaftor/Ivacaftor ELX/TEZ/IVA
- Pharmaceutical form
- GRANULES
- Route of administration
- ORAL
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 100 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- VERTEX PHARMACEUTICALS, INCORPORATED
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/18/2116
Kalydeco 59.5 mg granules in sachet
PRD10980411 · 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
- ORAL SOLUTION
- Route of administration
- ORAL
- Max daily dose
- 59.5 mg milligram(s)
- Max total dose
- 59.5 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Authorised
- ATC code
- R07AX02 — -
- Marketing authorisation
- EU/1/12/782/008
- 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
- Yes
- Modification description
- Modified strength
VX-445/VX-661/VX-770 fixed-dose combination granules
PRD8170957 · Product
- Active substance
- Tezacaftor
- Other product name
- VX-445/TEZ/IVA VX-445/Tezacaftor/Ivacaftor Elexacaftor/Tezacaftor/Ivacaftor ELX/TEZ/IVA
- Pharmaceutical form
- GRANULES
- Route of administration
- ORAL
- Max daily dose
- 80 mg milligram(s)
- Max total dose
- 80 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- VERTEX PHARMACEUTICALS, INCORPORATED
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/18/2116
PRD9088744 · Product
- Active substance
- Ivacaftor
- Pharmaceutical form
- GRANULES
- Route of administration
- ORAL
- Max daily dose
- 59.5 mg milligram(s)
- Max total dose
- 59.5 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- VERTEX PHARMACEUTICALS, INCORPORATED
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/08/556
PRD888530 · Product
- Active substance
- Ivacaftor
- Other product name
- Ivacaftor, 50mg
- Pharmaceutical form
- GRANULES
- Route of administration
- ORAL
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 50 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- VERTEX PHARMACEUTICALS, INCORPORATED
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/08/556
PRD888529 · Product
- Active substance
- Ivacaftor
- Other product name
- Ivacaftor, 75mg
- Pharmaceutical form
- GRANULES
- Route of administration
- ORAL
- Max daily dose
- 75 mg milligram(s)
- Max total dose
- 75 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- VERTEX PHARMACEUTICALS, INCORPORATED
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/08/556
PRD9662149 · Product
- Active substance
- Tezacaftor
- Pharmaceutical form
- GRANULES
- Route of administration
- ORAL
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- VERTEX PHARMACEUTICALS, INCORPORATED
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/18/2116
Kalydeco 50 mg granules in sachet
PRD3450695 · 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
- GRANULES
- Route of administration
- ORAL
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 50 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Authorised
- ATC code
- R07AX02 — -
- Marketing authorisation
- EU/1/12/782/003
- 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
- Yes
- Modification description
- Modified strength
PRD9662148 · Product
- Active substance
- Tezacaftor
- Pharmaceutical form
- GRANULES
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- VERTEX PHARMACEUTICALS, INCORPORATED
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/18/2116
Kaftrio 75 mg/50 mg/100 mg granules in sachet
PRD10968651 · 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
- ORAL SOLUTION
- Route of administration
- ORAL
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 100 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Authorised
- ATC code
- R07AX32 — -
- Marketing authorisation
- EU/1/20/1468/004
- 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
- Yes
- Modification description
- Modified strength
Kalydeco 25 mg granules in sachet
PRD7765989 · 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
- GRANULES
- Route of administration
- ORAL
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 25 mg milligram(s)
- Max treatment duration
- 96 Week(s)
- Authorisation status
- Authorised
- ATC code
- R07AX02 — -
- Marketing authorisation
- EU/1/12/782/006
- 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
- Yes
- Modification description
- Modified strength
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Vertex Pharmaceuticals Inc.
- Sponsor organisation
- Vertex Pharmaceuticals Inc.
- Address
- 50 Northern Avenue
- City
- Boston
- Postcode
- 02210-1862
- Country
- United States
Scientific contact point
- Organisation
- Vertex Pharmaceuticals Inc.
- Contact name
- Clinical Trials and Medical Info
Public contact point
- Organisation
- Vertex Pharmaceuticals Inc.
- Contact name
- Clinical Trials and Medical Info
Locations
3 EU/EEA countries · 5 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruitment ended | 3 | 1 |
| Germany | Ongoing, recruitment ended | 9 | 3 |
| Netherlands | Ongoing, recruitment ended | 3 | 1 |
| Rest of world
Canada, Switzerland, Australia
|
— | 35 | — |
Investigational sites
Rigshospitalet
CF Center, Copenhagen and Pediatric Pulmonary Unit Pediatric Department 5003, Blegdamsvej 9, 2100, Copenhagen Oe
Charite Universitaetsmedizin Berlin KöR
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Augustenburger Platz 1, Wedding, Berlin
Medizinische Hochschule Hannover
Pediatric Pneumology, Allergology and Neonatology, Carl-Neuberg-Strasse 1, Gross Buchholz, Hanover
Universitaetsklinikum Essen AöR
Pediatric Pulmonology, Hufelandstrasse 55, Holsterhausen, Essen
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department of Pediatrics, division of Respiratory Medicine and Allergology, Dr. Molewaterplein 40, 3015 GD, Rotterdam
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2025-01-08 | 2025-01-30 | 2025-09-04 | ||
| Germany | 2025-01-14 | 2025-02-03 | 2025-09-04 | ||
| Netherlands | 2025-01-24 | 2025-02-14 | 2025-09-04 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 19 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023-509563-24-00_redacted | 2 |
| Recruitment arrangements (for publication) | K1 Recruitment Arrangements_Denmark | 1 |
| Recruitment arrangements (for publication) | K1 Recruitment Arrangements_Germany | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_NL | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main Parent_Denmark_da_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main Parent_NL_nl_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF MBW Optional Sub-study Parent_Denmark_da | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF MBW Optional Sub-study Parent_NL_nl | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Parent Greenphire_NL_nl | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Parent Privacy_Denmark_da | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main Parent_Germany_de_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_MBW Optional Sub-study Parent_Germany_de | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Parent Greenphire_Germany_de | 1.0 |
| Subject information and informed consent form (for publication) | L2_SIS and ICF Tool_Denmark_da_redacted | 1 |
| Subject information and informed consent form (for publication) | L2_SIS and ICF Tool_NL_nl_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L2_SIS and ICF_Tool_Germany_de_redacted | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_DE 2023-509563-24-00_redacted | 2 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ENG 2023-509563-24-00_redacted | 2 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_NL 2023-509563-24-00_redacted | 2 |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-19 | Germany | Acceptable 2024-10-21
|
2024-10-21 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-11-05 | Germany | Acceptable 2024-10-21
|
2024-11-05 |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-11-08 | Acceptable | 2024-11-21 | |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2024-12-06 | Acceptable | 2024-12-06 | |
| 5 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-02-28 | Germany | Acceptable 2025-05-14
|
2025-05-15 |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-08-19 | Germany | Acceptable 2025-05-14
|
2025-08-19 |