Cystic FibrosisPhase 2NCT03119649
A Study to Evaluate Multiple Doses of GLPG2222 in Adult Subjects With Cystic Fibrosis
A Phase 2 study testing GLPG2222 50 mg, GLPG2222 100 mg and GLPG2222 200 mg in people with Cystic Fibrosis, run by Lakefront Biotherapeutics NV at 23 sites in 6 countries.
Trial summary
This is a Phase IIa, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate 4 different doses of GLPG2222 administered for 4 weeks to adult subjects with a confirmed diagnosis of CF and homozygous for the F508del Cystic Fibrosis Transmembrane conductance Regulator (CFTR) mutation. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- GLPG2222 50 mg, GLPG2222 100 mg and GLPG2222 200 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 23 sitesin 6 countries
- Study dates
- 18 Mar 2017to 19 Oct 2017
- 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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subject ≥ 18 years of age, on the day of signing the Informed Consent Form (ICF).
- A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation
- Weight ≥ 40 kg.
- Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline
- Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening
Who cannot join
- History of clinically meaningful unstable or uncontrolled chronic disease that makes the subject unsuitable for inclusion in the study in the opinion of the investigator.
- Unstable pulmonary status or respiratory tract infection requiring a change in therapy within 4 weeks of baseline.
- Need for supplemental oxygen during the day, and >2 liters per minute (LPM) while sleeping.
- Use of CFTR modulator therapy (e.g. lumacaftor or ivacaftor) within 4 weeks prior to the first study drug administration.
- History of hepatic cirrhosis with portal hypertension.
- Abnormal liver function test at screening; defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/ or alkaline phosphatase and/or gamma-glutamyl transferase (GGT) ≥ 3x the upper limit of normal (ULN); and/or total bilirubin (>1.5 times ULN)
- Estimated creatinine clearance < 60 mL/min using the Cockcroft-Gault formula at screening.
Trial locations and contacts
23 sites in 6 countries.
23 sites in 6 countries
United States7 sites
John Hopkins University School of Medicine
Baltimore, Maryland, 21205
Medical University of South Carolina
Charleston, South Carolina, 29425
Child Health Research Unit at UAB
Chatom, Alabama, 35233
Cystic Fibrosis Center of Chicago
Glenview, Illinois, 60026
University of Arkansas for medical Sciences
Little Rock, Arkansas, 72205
Central Florida Pulmonary Group
Orlando, Florida, 32803
Maine Medical Center
Portland, Maine, 04102
Belgium4 sites
UZ Antwerpen
Antwerp
UZ Brussel
Brussels
UZ Gent
Ghent
UZ Leuven
Leuven
Netherlands4 sites
AMC Amsterdam
Amsterdam
Erasmus medisch centrum
Rotterdam
Haga Ziekenhuis
The Hague
UMC Utrecht
Utrecht
United Kingdom4 sites
Papworth Hospital
Cambridge
St James University Hospital
Leeds
Liverpool Heart and Chest Hospital
Liverpool
Southampton general Hospital
Southampton
Spain3 sites
Hospital Universitari Vall d'Hebron
Barcelona
Hospital Universitario La Paz
Madrid
Hospital Universitarii Plitecnic La Fe
Valencia
About this study
Official title: A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate Multiple Doses of GLPG2222 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del Mutation
This is a Phase IIa, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate 4 different doses of GLPG2222 administered for 4 weeks to adult subjects with a confirmed diagnosis of CF and homozygous for the F508del Cystic Fibrosis Transmembrane conductance Regulator (CFTR) mutation.
- Conditions
- Cystic Fibrosis
- Being tested
- GLPG2222 50 mg, GLPG2222 100 mg, Placebo, GLPG2222 200 mg, GLPG2222 400 mg
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GLPG2222 50 mgDrug
Oral tablet(s) containing GLPG2222
GLPG2222 100 mgDrug
Oral tablet(s) containing GLPG2222
PlaceboDrug
Matching oral tablet(s) containing placebo
GLPG2222 200 mgDrug
Oral tablet(s) containing GLPG2222
GLPG2222 400 mgDrug
Oral tablet(s) containing GLPG2222
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: GLPG2222 50 mg once daily (QD) | Experimental | Participants received a single GLPG2222 50 mg tablet and two matching placebo tablets orally, QD for 29 days. Receives: Drug: GLPG2222 50 mg; Drug: Placebo |
| Cohort A: GLPG2222 100 mg QD | Experimental | Participants received a single GLPG2222 100 mg tablet and two matching placebo tablets orally, QD for 29 days. Receives: Drug: GLPG2222 100 mg; Drug: Placebo |
| Cohort B: GLPG2222 200 mg QD | Experimental | Participants received two GLPG2222 100 mg tablets and one matching placebo tablet orally, QD for 29 days. Receives: Drug: Placebo; Drug: GLPG2222 200 mg |
| Cohort B: GLPG2222 400 mg QD | Experimental | Participants received two GLPG2222 150 mg tablets and one GLPG2222 100 mg tablet orally, QD for 29 days. Receives: Drug: Placebo; Drug: GLPG2222 400 mg |
| Cohort A Placebo | Placebo comparator | Participants received three matching placebo tablets, orally, QD for 29 days. Receives: Drug: Placebo |
| Cohort B Placebo | Placebo comparator | Participants received three matching placebo tablets, orally, QD for 29 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events
Number of participants with any treatment-emergent adverse events (TEAEs) and serious or treatment-related TEAEs, as well as number of patients with TEAEs by worst intensity reported (mild, moderate, or severe).
Measured: First administration (Day 1) through Follow-up (Day 43)
Secondary outcomes (7)
Mean Change From Baseline in Sweat Chloride Concentration at Day 29
Two sweat collections, one from each arm, were obtained. Mean sweat chloride concentration was determined from both arms and measured as millimoles per liter (mmol/L). Baseline was defined as the predose value on Day 1 (or the last non-missing predose measurement).
Measured: Prior to dosing on Days 1 and 29, or at early discontinuation
Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29
Percent predicted FEV1 for age, gender, and height was determined from standardized spirometry assessments and estimated using the 2012 Global Lungs Initiative equation. Baseline was defined as the last non-missing predose assessment on Day 1.
Measured: Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation
Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. The respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), derived from Questions 40, 41, 42, 45, and 46 if at least 50% of the questions had non-missing data. The scale score ranged from 0-100; higher scores indicated fewer symptoms and better health-related quality of life with a negative change indicating a worsening of symptoms. A change of 4 is considered clinically relevant.
Measured: Prior to dosing on Days 1 and 29, or at early discontinuation
Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222
Maximum concentration of GLPG2222 after multiple dosing (ng/ML), obtained directly from the observed concentration versus time data. All pharmacokinetic (PK) parameters were determined from Day 15; Day 29 data were determined if the participant was not available for full PK profiling on Day 15.
Measured: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL)
Plasma concentration of GLPG2222 observed at pre-dose (ng/mL), obtained directly from the observed concentration versus time data. Ctrough was calculated using both Day 15 and Day 29 PK data.
Measured: Days 15 and 29 (predose)
Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h])
Time of occurrence of maximum concentration of GLPG2222 after multiple dosing (h), obtained directly from the observed concentration versus time data. All PK parameters were determined from Day 15; Day 29 data were determined if the participant was not available for full PK profiling on Day 15.
Measured: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Mean Area Under the Concentration-Time Curve From Time 0 up to 24 Hours Following Multiple Dosing (AUC[0-t]; ng.h/mL) of GLPG2222
Area under the concentration-time curve from time 0 up to 24 hours following multiple dosing (ng.h/mL), calculated by linear up/log down trapezoidal summation. All PK parameters were determined from Day 15; Day 29 data were determined if the participant was not available for full PK profiling on Day 15.
Measured: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2017
- Study start18 Mar 2017
- Primary completion19 Oct 2017
- Study completion19 Oct 2017
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 (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- 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
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lakefront Biotherapeutics NV
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Olivier Van Steen, MD, MBA, Study director, Lakefront Biotherapeutics NV
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03119649
- Sponsor's protocol ID
- GLPG2222-CL-202
- Status last verified
- Oct 2018
- First submitted
- 11 Apr 2017
- Last updated
- 16 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Bell SC, Barry PJ, De Boeck K, Drevinek P, Elborn JS, Plant BJ, Minic P, Van Braeckel E, Verhulst S, Muller K, Kanters D, Bellaire S, de Kock H, Geller DE, Conrath K, Van de Steen O, van der Ent K. CFTR activity is enhanced by the novel corrector GLPG2222, given with and without ivacaftor in two randomized trials. J Cyst Fibros. 2019 Sep;18(5):700-707. doi: 10.1016/j.jcf.2019.04.014. Epub 2019 May 3.
PubMed 31056441
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate Multiple Doses of GLPG2222 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del Mutation
- ClinicalTrials.gov ID
- NCT03119649
- Acronym / sponsor ID
- GLPG2222-CL-202
- Conditions
- Cystic Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Lakefront Biotherapeutics NVIndustry (pharma, biotech, devices)
- Study start
- 18 Mar 2017 (actual)
- Primary completion
- 19 Oct 2017 (actual)
- Study completion
- 19 Oct 2017 (actual)
- First posted
- 18 Apr 2017 (actual)
- Results
- Posted 16 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase IIa, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate 4 different doses of GLPG2222 administered for 4 weeks to adult subjects with a confirmed diagnosis of CF and homozygous for the F508del Cystic Fibrosis Transmembrane conductance Regulator (CFTR) mutation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort A: GLPG2222 50 mg once daily (QD) | Experimental | Drug: GLPG2222 50 mg, Drug: PlaceboParticipants received a single GLPG2222 50 mg tablet and two matching placebo tablets orally, QD for 29 days. |
| Cohort A: GLPG2222 100 mg QD | Experimental | Drug: GLPG2222 100 mg, Drug: PlaceboParticipants received a single GLPG2222 100 mg tablet and two matching placebo tablets orally, QD for 29 days. |
| Cohort B: GLPG2222 200 mg QD | Experimental | Drug: Placebo, Drug: GLPG2222 200 mgParticipants received two GLPG2222 100 mg tablets and one matching placebo tablet orally, QD for 29 days. |
| Cohort B: GLPG2222 400 mg QD | Experimental | Drug: Placebo, Drug: GLPG2222 400 mgParticipants received two GLPG2222 150 mg tablets and one GLPG2222 100 mg tablet orally, QD for 29 days. |
| Cohort A Placebo | Placebo comparator | Drug: PlaceboParticipants received three matching placebo tablets, orally, QD for 29 days. |
| Cohort B Placebo | Placebo comparator | Drug: PlaceboParticipants received three matching placebo tablets, orally, QD for 29 days. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female subject ≥ 18 years of age, on the day of signing the Informed Consent Form (ICF).
- A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation
- Weight ≥ 40 kg.
- Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline
- Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening
Key exclusion criteria (7 listed)
- History of clinically meaningful unstable or uncontrolled chronic disease that makes the subject unsuitable for inclusion in the study in the opinion of the investigator.
- Unstable pulmonary status or respiratory tract infection requiring a change in therapy within 4 weeks of baseline.
- Need for supplemental oxygen during the day, and >2 liters per minute (LPM) while sleeping.
- Use of CFTR modulator therapy (e.g. lumacaftor or ivacaftor) within 4 weeks prior to the first study drug administration.
- History of hepatic cirrhosis with portal hypertension.
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 |
|---|---|---|
| GLPG2222 50 mgOral tablet(s) containing GLPG2222 | Drug | Cohort A: GLPG2222 50 mg once daily (QD) |
| GLPG2222 100 mgOral tablet(s) containing GLPG2222 | Drug | Cohort A: GLPG2222 100 mg QD |
| PlaceboMatching oral tablet(s) containing placebo | Drug | Cohort A Placebo, Cohort A: GLPG2222 100 mg QD, Cohort A: GLPG2222 50 mg once daily (QD), Cohort B Placebo, Cohort B: GLPG2222 200 mg QD, Cohort B: GLPG2222 400 mg QD |
| GLPG2222 200 mgOral tablet(s) containing GLPG2222 | Drug | Cohort B: GLPG2222 200 mg QD |
| GLPG2222 400 mgOral tablet(s) containing GLPG2222 | Drug | Cohort B: GLPG2222 400 mg QD |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events
Time frame: First administration (Day 1) through Follow-up (Day 43)
Number of participants with any treatment-emergent adverse events (TEAEs) and serious or treatment-related TEAEs, as well as number of patients with TEAEs by worst intensity reported (mild, moderate, or severe).
7 secondary outcomes
Mean Change From Baseline in Sweat Chloride Concentration at Day 29
Time frame: Prior to dosing on Days 1 and 29, or at early discontinuation
Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29
Time frame: Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation
Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29
Time frame: Prior to dosing on Days 1 and 29, or at early discontinuation
Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222
Time frame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL)
Time frame: Days 15 and 29 (predose)
Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h])
Time frame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Mean Area Under the Concentration-Time Curve From Time 0 up to 24 Hours Following Multiple Dosing (AUC[0-t]; ng.h/mL) of GLPG2222
Time frame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31056441Bell SC, Barry PJ, De Boeck K, Drevinek P, Elborn JS, Plant BJ, Minic P, Van Braeckel E, Verhulst S, Muller K, Kanters D, Bellaire S, de Kock H, Geller DE, Conrath K, Van de Steen O, van der Ent K. CFTR activity is enhanced by the novel corrector GLPG2222, given with and without ivacaftor in two randomized trials. J Cyst Fibros. 2019 Sep;18(5):700-707. doi: 10.1016/j.jcf.2019.04.014. Epub 2019 May 3.
- Individual participant dataSharing planned: Undecided
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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.
Olivier Van Steen, MD, MBA study director
Lakefront Biotherapeutics NV
23 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GLPG2222 50 mg, GLPG2222 100 mg and GLPG2222 200 mg in people with Cystic Fibrosis, run by Lakefront Biotherapeutics NV at 23 sites in 6 countries.
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 5 inclusion and 7 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 16 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, Belgium, Netherlands, United Kingdom, Spain and 1 more country. 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 16 Nov 2018). 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?
Number of Participants With Treatment-Emergent Adverse Events (time frame: First administration (Day 1) through Follow-up (Day 43)). 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 NCT03119649, which also lists 1 linked publication.
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 16 Nov 2018.