Cystic FibrosisPhase 2NCT03625466
A Study to Explore the Impact of Lumacaftor/Ivacaftor on Disease Progression in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del
A Phase 2 study testing LUM/IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 5 sites in Germany.
Trial summary
This study will explore the impact of lumacaftor/ivacaftor (LUM/IVA) on disease progression in subjects aged 2 through 5 years with cystic fibrosis (CF), homozygous for F508del (F/F). Read more about this study
- Who is it for?
- Ages 2 to 5 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- LUM/IVA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 5 sitesGermany
- Study dates
- 10 Aug 2018to 7 Oct 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Subjects with confirmed diagnosis of CF.
- Homozygous for F508del (F/F).
- Subjects who weigh ≥8 kg without shoes and wearing light clothing at the Screening Visit.
Who cannot join
- Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject.
- Solid organ or hematological transplantation.
- History of any illness or comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study.
- Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Germany5 sites
Charite Paediatric Pulmonology Department
Berlin
Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
Giessen
Hannover Medical School
Hanover
Heidelberg Cystic Fibrosis Center
Heidelberg
Universitatsklinikum Schleswig-Holstein, Klinik für Kinder- und Jugendmedizin
Lübeck
About this study
Official title: An Exploratory Phase 2, 2-part, Randomized, Double-blind, Placebo-controlled Study With a Long-term, Open-label Period to Explore the Impact of Lumacaftor/Ivacaftor on Disease Progression in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del
This study will explore the impact of lumacaftor/ivacaftor (LUM/IVA) on disease progression in subjects aged 2 through 5 years with cystic fibrosis (CF), homozygous for F508del (F/F).
- Conditions
- Cystic Fibrosis
- Being tested
- LUM/IVA, Placebo
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LUM/IVADrug
Also called Lumacaftor/Ivacaftor, VX-809/VX-770
FDC tablets or granules for oral administration.
LUM/IVADrug
Also called Lumacaftor/Ivacaftor, VX-809/VX-770
FDC granules for oral administration.
PlaceboDrug
Placebo matched to LUM/IVA for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Placebo | Placebo comparator | Participants received placebo matched to LUM/IVA in placebo-controlled period for 48 weeks. Receives: Drug: Placebo |
| Part 1: LUM/IVA | Experimental | Participants weighing less than (<)14 kilograms (kg) at screening received LUM 100 milligrams (mg)/IVA 125 mg fixed-dose combination (FDC) every 12 hours (q12h) in placebo-controlled period for 48 weeks. Participants weighing greater than or equals to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h in placebo-controlled period for 48 weeks. Receives: Drug: LUM/IVA |
| Part 2: Overall LUM/IVA | Experimental | Participants who received either placebo or LUM/IVA in placebo-controlled period administered LUM/IVA (either LUM 100 mg/IVA 125 mg FDC q12h or LUM 150 mg/IVA 188 mg FDC q12h as per their body weight for participants <6 years of age at week 48 and LUM 200 mg/IVA 250 mg FDC q12h regardless of their body weight for participants >=6 years of age at week 48) in open-label period for 48 weeks. Receives: Drug: LUM/IVA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Absolute Change From Baseline in MRI Global Chest Score at Week 48
MRI scans assessed semi-quantitatively via a standardized chest MRI scoring system. Each participant had 6 lobes scored using 7 scoring parameters:1) Bronchiectasis/wall thickening 2) Mucus plugging 3) Abscesses/sacculations 4) Consolidations 5) Special findings 6)Mosaic pattern 7) Perfusion abnormalities. For each of 7 parameter, there were scores of 6 lobes (score of each lobe : 0= normal value, 1 = <50% of lobe involved and 2 = >=50% of lobe involved). MRI global score was calculated as sum of parameters 1 to 7. MRI total score is ranged from 0-84. Higher score indicate more lobe involvement.
Measured: From Baseline at Week 48
Secondary outcomes (4)
Part 1: Absolute Change in Lung Clearance Index2.5 (LCI2.5) Through Week 48
LCI2.5 represents the number of lung turnovers required to reduce the end-tidal inert gas concentration to 1/40th of its starting value.
Measured: From Baseline Through Week 48
Part 1: Absolute Change in Weight-for-age Z-score at Week 48
The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Measured: From Baseline at Week 48
Part 1: Absolute Change in Stature-for-age Z-score at Week 48
The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Measured: From Baseline at Week 48
Part 1: Absolute Change in Body Mass Index (BMI)-For-age Z-score at Week 48
BMI was defined as weight in kilogram (kg) divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Measured: From Baseline at Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2018
- Study start10 Aug 2018
- Primary completion9 Oct 2020
- Study completion7 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03625466
- Sponsor's protocol ID
- VX16-809-121
- Other IDs
- 2017-003761-99, 2017
- Status last verified
- Oct 2022
- First submitted
- 7 Aug 2018
- Last updated
- 2 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Stahl M, Roehmel J, Eichinger M, Doellinger F, Naehrlich L, Kopp MV, Dittrich AM, Sommerburg O, Ray P, Maniktala A, Xu T, Conner S, Joshi A, Mascia M, Wielputz MO, Mall MA. Long-Term Impact of Lumacaftor/Ivacaftor Treatment on Cystic Fibrosis Disease Progression in Children 2-5 Years of Age Homozygous for F508del-CFTR: A Phase 2, Open-Label Clinical Trial. Ann Am Thorac Soc. 2024 Nov;21(11):1550-1559. doi: 10.1513/AnnalsATS.202402-201OC.
PubMed 39173175Stahl M, Roehmel J, Eichinger M, Doellinger F, Naehrlich L, Kopp MV, Dittrich AM, Lee C, Sommerburg O, Tian S, Xu T, Wu P, Joshi A, Ray P, Duncan ME, Wielputz MO, Mall MA. Effects of Lumacaftor/Ivacaftor on Cystic Fibrosis Disease Progression in Children 2 through 5 Years of Age Homozygous for F508del-CFTR: A Phase 2 Placebo-controlled Clinical Trial. Ann Am Thorac Soc. 2023 Aug;20(8):1144-1155. doi: 10.1513/AnnalsATS.202208-684OC.
PubMed 36943405
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Phase 2, 2-part, Randomized, Double-blind, Placebo-controlled Study With a Long-term, Open-label Period to Explore the Impact of Lumacaftor/Ivacaftor on Disease Progression in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del
- ClinicalTrials.gov ID
- NCT03625466
- Acronym / sponsor ID
- VX16-809-121
- Conditions
- Cystic Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 10 Aug 2018 (actual)
- Primary completion
- 9 Oct 2020 (actual)
- Study completion
- 7 Oct 2021 (actual)
- First posted
- 10 Aug 2018 (actual)
- Results
- Posted 8 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will explore the impact of lumacaftor/ivacaftor (LUM/IVA) on disease progression in subjects aged 2 through 5 years with cystic fibrosis (CF), homozygous for F508del (F/F).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1: Placebo | Placebo comparator | Drug: PlaceboParticipants received placebo matched to LUM/IVA in placebo-controlled period for 48 weeks. |
| Part 1: LUM/IVA | Experimental | Drug: LUM/IVAParticipants weighing less than (<)14 kilograms (kg) at screening received LUM 100 milligrams (mg)/IVA 125 mg fixed-dose combination (FDC) every 12 hours (q12h) in placebo-controlled period for 48 weeks. Participants weighing greater than or equals to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h in placebo-controlled period for 48 weeks. |
| Part 2: Overall LUM/IVA | Experimental | Drug: LUM/IVAParticipants who received either placebo or LUM/IVA in placebo-controlled period administered LUM/IVA (either LUM 100 mg/IVA 125 mg FDC q12h or LUM 150 mg/IVA 188 mg FDC q12h as per their body weight for participants <6 years of age at week 48 and LUM 200 mg/IVA 250 mg FDC q12h regardless of their body weight for participants >=6 years of age at week 48) in open-label period for 48 weeks. |
Who may qualify
- Ages
- 2 to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Subjects with confirmed diagnosis of CF.
- Homozygous for F508del (F/F).
- Subjects who weigh ≥8 kg without shoes and wearing light clothing at the Screening Visit.
Key exclusion criteria (4 listed)
- Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject.
- Solid organ or hematological transplantation.
- History of any illness or comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study.
- Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LUM/IVAAlso: Lumacaftor/Ivacaftor, VX-809/VX-770FDC tablets or granules for oral administration. | Drug | Part 2: Overall LUM/IVA |
| LUM/IVAAlso: Lumacaftor/Ivacaftor, VX-809/VX-770FDC granules for oral administration. | Drug | Part 1: LUM/IVA |
| PlaceboPlacebo matched to LUM/IVA for oral administration. | Drug | Part 1: Placebo |
Primary outcome
Part 1: Absolute Change From Baseline in MRI Global Chest Score at Week 48
Time frame: From Baseline at Week 48
MRI scans assessed semi-quantitatively via a standardized chest MRI scoring system. Each participant had 6 lobes scored using 7 scoring parameters:1) Bronchiectasis/wall thickening 2) Mucus plugging 3) Abscesses/sacculations 4) Consolidations 5) Special findings 6)Mosaic pattern 7) Perfusion abnormalities. For each of 7 parameter, there were scores of 6 lobes (score of each lobe : 0= normal value, 1 = <50% of lobe involved and 2 = >=50% of lobe involved). MRI global score was calculated as sum of parameters 1 to 7. MRI total score is ranged from 0-84. Higher score indicate more lobe involvement.
4 secondary outcomes
Part 1: Absolute Change in Lung Clearance Index2.5 (LCI2.5) Through Week 48
Time frame: From Baseline Through Week 48
Part 1: Absolute Change in Weight-for-age Z-score at Week 48
Time frame: From Baseline at Week 48
Part 1: Absolute Change in Stature-for-age Z-score at Week 48
Time frame: From Baseline at Week 48
Part 1: Absolute Change in Body Mass Index (BMI)-For-age Z-score at Week 48
Time frame: From Baseline at Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39173175Stahl M, Roehmel J, Eichinger M, Doellinger F, Naehrlich L, Kopp MV, Dittrich AM, Sommerburg O, Ray P, Maniktala A, Xu T, Conner S, Joshi A, Mascia M, Wielputz MO, Mall MA. Long-Term Impact of Lumacaftor/Ivacaftor Treatment on Cystic Fibrosis Disease Progression in Children 2-5 Years of Age Homozygous for F508del-CFTR: A Phase 2, Open-Label Clinical Trial. Ann Am Thorac Soc. 2024 Nov;21(11):1550-1559. doi: 10.1513/AnnalsATS.202402-201OC.
- Derived from this study: PubMed 36943405Stahl M, Roehmel J, Eichinger M, Doellinger F, Naehrlich L, Kopp MV, Dittrich AM, Lee C, Sommerburg O, Tian S, Xu T, Wu P, Joshi A, Ray P, Duncan ME, Wielputz MO, Mall MA. Effects of Lumacaftor/Ivacaftor on Cystic Fibrosis Disease Progression in Children 2 through 5 Years of Age Homozygous for F508del-CFTR: A Phase 2 Placebo-controlled Clinical Trial. Ann Am Thorac Soc. 2023 Aug;20(8):1144-1155. doi: 10.1513/AnnalsATS.202208-684OC.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LUM/IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 5 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Absolute Change From Baseline in MRI Global Chest Score at Week 48 (time frame: From Baseline at Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03625466, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2022.