Summary
EudraCT Number:2019-004676-18
Sponsor's Protocol Code Number:213340
National Competent Authority:Netherlands - Competent Authority
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2020-11-13
Trial results
A. Protocol Information
A.1Member State ConcernedNetherlands - Competent Authority
A.2EudraCT number2019-004676-18
A.3Full title of the trial
Differences in effect of treatment with mepolizumab and benralizumab on resident and inflammatory eosinophils
Het verschil in effect van behandeling met mepolizumab en benralizumab op residente en inflammatoire eosinofiele granulocyten
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Comparison of the mode of action of two anti-asthma drugs, mepolizumab and benralizumab, during treatment of asthma patients with moderate to severe asthma.
Vergelijking van de werkingsmechanismen van twee anti-astma medicijnen, mepolizumab en benralizumab, tijdens de behandeling van patiënten met matig tot ernstig astma.
A.3.2Name or abbreviated title of the trial where available
Dimension
Dimensie
A.4.1Sponsor's protocol code number213340
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorUniversity Medical Center Utrecht
B.1.3.4CountryNetherlands
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportGlaxoSmithKline
B.4.2CountryUnited Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationUniversity Medical Center Utrecht
B.5.2Functional name of contact pointHead of lab of Respiratory Medicine
B.5.3 Address:
B.5.3.1Street AddressHeidelberglaan 100
B.5.3.2Town/ cityUtrecht
B.5.3.3Post code3584CX
B.5.3.4CountryNetherlands
B.5.4Telephone number31887556180
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Nucala
D.2.1.1.2Name of the Marketing Authorisation holderGlaxoSmithKline
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameNucala
D.3.2Product code SB-240563
D.3.4Pharmaceutical form Solution for injection in pre-filled pen
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPSubcutaneous use
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Yes
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Fasenra
D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameFasenra
D.3.2Product code IW-8405
D.3.4Pharmaceutical form Solution for injection in pre-filled pen
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPSubcutaneous use
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Yes
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another 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.1.1Medical condition(s) being investigated
severe eosinophilic asthma
ernstig eosinofiel astma
E.1.1.1Medical condition in easily understood language
Treatment of patients with severe asthma that do not sufficiently respond to current treatment
Behandeling van patiënten met ernstig asthma die niet goed op huidige therapie responderen
E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level PT
E.1.2Classification code 10003553
E.1.2Term Asthma
E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
Understanding the differences in mechanism of treatment between nucala and fasenra
Het begrijpen van de verschillen in werkingsmechanisme tussen nucal en fasenra
E.2.2Secondary objectives of the trial
1. To determine the kinetics of eosinophils in rectal tissue in patients treated with either nucala or fasenra

2. To study the effects of nucala on tissue eosinphils of patients previously treated with fasenra and vice versa
1. Het vaststellen van de kinetiek van rectaalweefsel eosinofiele granulocyten in patienten die worden behandeld met nucala of fasenra.

2. Het bestuderen van de effecten van nucala op eosinofiele granulocyten in rectaalweefsel in patienten die eerst worden behandeld met fasenra en vice versa
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
•Age ≥ 18
•Diagnosis of severe refractory eosinophilic asthma
•Eligible for mepolizumab or benralizumab therapy according the national recommendations for severe asthma of the Dutch society for lung diseases and tuberculosis (NVALT guideline 2013): Patients with asthma, for whom alternative diagnoses are excluded, comorbidity optimally treated, provoking factors minimized and therapy compliance optimized, but despite this still have insufficient asthma control (≥ 1.5 ACQ-7 or other questionnaire) or frequent (≥2 annually) severe exacerbations (systemic CS needed) while routinely using high-dose asthma medication (≥ 1000 mcg/day fluticasone propionate equivalent and/or daily OCS in combination with LABA or other controller medication); or patients who can achieve asthma control only with systemic CS and are therefore are risk for adverse effects or the corticosteroids.
•Treated with mepolizumab or benralizumab for at least 4 months.
•Before treatment with biologics a blood eosinophilia (≥ 150 eosinophils/microl blood) irrespective of steroid use
•Age ≥ 18
•Diagnosis of severe refractory eosinophilic asthma
•Eligible for mepolizumab or benralizumab therapy according the national recommendations for severe asthma of the Dutch society for lung diseases and tuberculosis (NVALT guideline 2013): Patients with asthma, for whom alternative diagnoses are excluded, comorbidity optimally treated, provoking factors minimized and therapy compliance optimized, but despite this still have insufficient asthma control (≥ 1.5 ACQ-7 or other questionnaire) or frequent (≥2 annually) severe exacerbations (systemic CS needed) while routinely using high-dose asthma medication (≥ 1000 mcg/day fluticasone propionate equivalent and/or daily OCS in combination with LABA or other controller medication); or patients who can achieve asthma control only with systemic CS and are therefore are risk for adverse effects or the corticosteroids.
•Treated with mepolizumab or benralizumab for at least 4 months.
•Before treatment with biologics a blood eosinophilia (≥ 150 eosinophils/microl blood) irrespective of steroid use
E.4Principal exclusion criteria
•Any infection (eg. HIV, Hepatitis, STDs)
•Insulin dependent diabetes
•Smoking at present or in the last 12 months and/or a past history of more than 10 pack years
•Proven allergic bronchopulmonary aspergillosis
•Auto-immune diseases
•Use of medication, excluding:
oAnticonceptives
oPain killers, if used on average less than once a week
•exuberant alcohol consumption (for males > 36 glasses per week, for females >24 glasses per week)
•Drug use
•History of cancer
•Use of biologicals other than mepolizumab or benralizumab
•daily oral steroid therapy during the three months preceding inclusion
•enige infectie (bijv. HIV, Hepatitis, SOAs)
•Insuline afhankelijke diabetes
•Roken gedurende de laatste 12 maanden of meer dan 10 pakjesjaren
•Aangetoonde allergische bronchopulmonale aspergillose
•Auto-immuun ziekte(n)
•Gebruik van geneesmiddelen anders dan
oAstma medicatie
oAnticonceptiva
oPijnstillers, wanneer gemiddeld gebruik minder dan één per week
•Overmatig alkoholgebruik (voor mannen > 36 glazen per week), voor vrouwen >24 glazen/week
•Gebruik van recreational drugs
•Kanker/genezen van kanker
•Gebruik van biologicals anders dan mepolizumab of benralizumab
•Dagelijks gebruik van orale steroiden gedurende drie maanden voor start van de studie
E.5 End points
E.5.1Primary end point(s)
The number of eosinophils in rectal tissue
Het aantal van eosinofielen in rectaal weelsel
E.5.1.1Timepoint(s) of evaluation of this end point
Biopsies will be taken only one time point in patients treated > 3 months with nucala or fasenra
Biopsies worden genomen éénmalig in patiënten behandeld > 3 maanden met nucala of fasenra
E.5.2Secondary end point(s)
1. Deuterium enrichment in DNA of tissue eosinophils

2. Het aantal van eosinofielen in rectaal weelsel
1. Deuterium verrijking in DNA van weefsel eosinofiele granulocyten

2. Het aantal van eosinofielen in rectaal weefsel
E.5.2.1Timepoint(s) of evaluation of this end point
1. Biopsies will be taken only one time point in patients treated > 3 months with nucala or fasenra

2. Biopsies will be taken t=0 (no treatment with biological), t=6 months after treatment with nucala or fasenra, cross-over, t=12 months after treatment with fasenra or nucala
1. Biopsies worden genomen éénmalig in patiënten behandeld > 3 maanden met nucala of fasenra

2. Biopsies worden genomen t=0 (geen behandeling met biological), t=6 maanden na behandeling met nucala of fasenra, cross-over, t=12 maanden na behandeling met fasenra of nucala
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy No
E.6.4Safety No
E.6.5Efficacy No
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence Yes
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) Yes
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind Yes
E.8.1.4Double blind No
E.8.1.5Parallel group Yes
E.8.1.6Cross over Yes
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) Yes
E.8.2.2Placebo No
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned Yes
E.8.4 The trial involves multiple sites in the Member State concerned No
E.8.5The trial involves multiple Member States No
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA No
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.7Trial has a data monitoring committee No
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
LVLS
LVLS
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years3
E.8.9.1In the Member State concerned months0
E.8.9.1In the Member State concerned days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 60
F.1.3Elderly (>=65 years) No
F.1.3.1Number of subjects for this age range: 12
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers Yes
F.3.2Patients Yes
F.3.3Specific vulnerable populations No
F.3.3.1Women of childbearing potential not using contraception Information not present in EudraCT
F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
F.3.3.3Pregnant women Information not present in EudraCT
F.3.3.4Nursing women Information not present in EudraCT
F.3.3.5Emergency situation Information not present in EudraCT
F.3.3.6Subjects incapable of giving consent personally Information not present in EudraCT
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state72
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
Patients are already on nucala or fazenra
Patienten gebruiken al nucala of fazenra
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2022-07-07
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2020-09-10
P. End of Trial
P.End of Trial StatusOngoing