Kliniske forsøg Nct side

Summary
EudraCT Number:2018-001571-21
Sponsor's Protocol Code Number:P18.037
National Competent Authority:Netherlands - Competent Authority
Clinical Trial Type:EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:2018-05-23
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedNetherlands - Competent Authority
A.2EudraCT number2018-001571-21
A.3Full title of the trial
Training immune functions through pharmacotherapeutic conditioning in
juvenile idiopathic arthritis
Training van immuunfuncties door middel van farmacotherapeutisch
conditioneren in juveniele idiopatische artritis
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Reducing side effects from methotrexate in juvenile arthritis treatment
Verminderen van bijwerkingen bij methotrexaat in de behandeling van jeugdreuma
A.3.2Name or abbreviated title of the trial where available
OPTI-MISS
OPTI-MISS
A.4.1Sponsor's protocol code numberP18.037
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 SponsorLeiden University
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 supportLeiden University, Institute of Psychology
B.4.2CountryNetherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationLeiden University
B.5.2Functional name of contact pointInstitute of Psychology
B.5.3 Address:
B.5.3.1Street AddressWassenaarseweg 52
B.5.3.2Town/ cityLeiden
B.5.3.3Post code2333 AK
B.5.3.4CountryNetherlands
B.5.6E-maila.evers@fsw.leidenuniv.nl
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
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 Methotrexate
D.2.1.1.2Name of the Marketing Authorisation holderSandoz BV
D.2.1.2Country which granted the Marketing AuthorisationNetherlands
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 nameMethotrexate
D.3.4Pharmaceutical form Tablet
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOral use
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
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) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
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
D.8 Placebo: 1
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboTablet
D.8.4Route of administration of the placeboOral use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Juvenile Idiopathic Arthritis
Juveniele Idiopathische Artritis
E.1.1.1Medical condition in easily understood language
Juvenile Arthritis
Jeugdreuma
E.1.1.2Therapeutic area Psychiatry and Psychology [F] - Psychological processes [F02]
MedDRA Classification
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
This study’s objective is to reduce MTX related side effects with pharmacotherapeutic conditioning, by using variable reinforcement principles in patients with JIA. Pharmacotherapeutic conditioning enables to alternate standard MTX dosing with lower MTX doses, by utilizing learning effects (conditioning). By this, children with JIA will be less affected by MTX related side effects, without compromising for its therapeutic efficacy. A reduction in side effects will be assessed by intolerance percentages as defined by a cutoff score of ≥ 6 on the Methotrexate Intolerance Severity Score (MISS) questionnaire.
Het doel van deze studie is om bijwerkingen te verminderen door middel van farmacotherapeutisch conditioneren bij patiënten met JIA. Farmacotherapeutisch conditioneren biedt de mogelijkheid om MTX doseringen af te wisselen met lagere doseringen. Door het afwisselend doseren wordt gebruik gemaakt van de leereffecten van het medicijn (conditioneren). Hierdoor zullen mogelijk minder kinderen last hebben van bijwerkingen doordat lagere MTX doseringen gebruikt kunnen worden voor de behandeling van JIA, zonder dat dit ten koste zal gaan van de ziekteactiviteit. Een verlaging in bijwerkingen zal gemeten worden aan de hand intolerantie percentages op basis van de Methotrexate Intolerance Severity Score (MISS) van 6 of hoger.
E.2.2Secondary objectives of the trial
Secondary outcome measures are achieving low disease activity as measured by the Juvenile Arthritis Disease Activity Score (JADAS < 3), side effects as determined by liver function and gastrointestinal bleeding, laboratory assessments (e.g., cytokine levels and myeloid-related proteins and MTX polyglutamates), and self-report outcomes as assessed by validated scales about pain and burden of disease.
Secundaire uitkomstmaten zijn het behalen van lage ziekteactiviteit, gemeten met de Juvenile Arthritis Disease Activity Score (JADAS < 3), bijwerkingen gemeten aan de hand van lever- en nierfuncties, laboratorium onderzoek (cytokine, myeloid-related proteines (MRP 8, 14) en MTX polyglutamaten gemeten uit rode bloedcellen) en standaard gevalideerde vragenlijsten voor klinisch gebruik waarin pijn en kwaliteit van leven worden gemeten.
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
- Age between 4 to 17 years (at the time of JIA diagnosis);
- Diagnosed with JIA by their physician as defined by the ILAR-classification;
- Able to speak or understand Dutch;
- Patients (or parents/guardians of the patient under the age of 12) are able to give informed consent;
- Achieve a good MTX response based on the JADAS (Juvenile Arthritis Disease Activity Score) assessing inactive disease scores at 6 months after MTX onset, with a score of 3 or lower or based on the pediatric rheumatologist's opinion.
- Leeftijd van 4 tot 17 jaar (op het moment dat diagnose JIA is gesteld);
- JIA diagnose door behandelend arts op basis van ILAR-classificatie;
- Vermogen om Nederlands te spreken of te begrijpen;
- De patiënt (of diens ouders/voogd tot 12 jaar) is in staat om geïnformeerd toestemming te geven;
- Goede respons op MTX behandeling na 6 maanden op basis van de JADAS (Juvenile Arthritis Disease Activity Score) met een score van 3 of lager (lage ziekte activiteit) of naar inzicht van de kinderreumatoloog.
E.4Principal exclusion criteria
- DMARD use at the moment of inclusion; or MTX experience previously
- Alternative route of MTX administration than oral (e.g. subcutaneous)
- Concomitant treatment with an experimental drug or procedure interfering with this study purposes
- Systemic JIA
- Development of uveitis which needs to be treated with a DMARD
- Elevated hepatic enzyme levels (serum aspartate transaminase [AST], serum alanine transaminase [ALT] > 2 times normal value)
- Bone marrow suppression as lymphocyte count <0.9×109/L, granulocyte count <1.5×109/L and/or thrombocyte count <20 × 109/L.39
- Serum creatinine levels > 150 umol/l or estimated creatinine clearance of < 75%
- Biologicals
- Gebruik van DMARD op het moment van inclusie; of eerdere ervaring met MTX
- Alternatieve wijze van MTX toediening dan oraal (bv. subcutaan)
- Gelijktijdige behandeling van een experimenteel medicijn of procedure welke interfereert met doel van het huidige onderzoek
- Systemische JIA
- Uveitis waarvoor DMARD benodigd is
- Verhoogde lever-enzym waarden (serum aspartate transaminase [AST], serum alanine transaminase [ALT] > 2 keer normale waarde)
- Beenmerg onderdrukking op basis van lymphocyte aantal <0.9×109/L, granulocyte aantal <1.5×109/L and/or thrombocyte aantal <20 × 109/L.39
- Serum creatinine waarden > 150 umol/l of geschatte creatinine klaring van < 75%
- Medicatiebehandeling met biologicals
E.5 End points
E.5.1Primary end point(s)
The primary outcome parameter is the difference in percentage of patients who experience MTX intolerance as defined by the Methotrexate Intolerance Severity Score (MISS) with a cut-off score of ≥ 6 between the control and intervention (conditioning) groups, after 9 months of interventon. The primary outcome measure MISS will be measured at month 15. The study will close with an end-of-study visit at month 18 where early flare-ups and side effects will be monitored.
De primaire uitkomstmaat is het percentage in MTX intolerantie na 9 maanden interventie, gemeten met de Methotrexate Intolerance Severity Score (MISS) met een cut-off score ≥ 6, vergeleken tussen de controle- en interventiegroep. De primaire uitkomstmaat MISS wordt op maand 15 gemeten. De studie zal sluiten met een end-of-study visit waarin wordt gekeken naar (vroege) flare-ups en ervaren bijwerkingen
E.5.1.1Timepoint(s) of evaluation of this end point
Month 15: Primary outcome measure, MISS
Month 15: Primaire uitkomstmaat, MISS
E.5.2Secondary end point(s)
Month 15: Secondary outcome measures: side effects as determined by liver function and gastrointestinal bleeding, laboratory assessments (e.g., cytokine levels and myeloid-related proteins and MTX polyglutamates), and self-report outcomes as assessed by validated scales about pain and burden of disease.

Month 18: Follow-up
Maand 15: Secundiare uitkomstmaten: JADAS, bijwerkingen gemeten aan de hand van lever- en nierfuncties, laboratorium onderzoek (cytokine, myeloid-related proteines (MRP 8, 14), MTX polyglutamaten gemeten uit rode bloedcellen) en standaard gevalideerde vragenlijsten voor klinisch gebruik waarin pijn en kwaliteit van leven worden gemeten.

Month 18: Follow-up
E.5.2.1Timepoint(s) of evaluation of this end point
Month 15 and 18
Month 15 and 18
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 Yes
E.6.4Safety No
E.6.5Efficacy No
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others Yes
E.6.13.1Other scope of the trial description
Pharmacotherapeutic approach will be used to reduce side effects
Farmacothereapeutische behandeling zal ingezet worden om bijwerkingen te verminderen.
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 No
E.8.1.4Double blind Yes
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other Yes
E.8.2.3.1Comparator description
standaard behandeling
care as usual
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned4
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 Yes
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 years1
E.8.9.1In the Member State concerned months6
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years1
E.8.9.2In all countries concerned by the trial months6
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 Yes
F.1.1Number of subjects for this age range: 132
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) Yes
F.1.1.5.1Number of subjects for this age range: 66
F.1.1.6Adolescents (12-17 years) Yes
F.1.1.6.1Number of subjects for this age range: 66
F.1.2Adults (18-64 years) No
F.1.3Elderly (>=65 years) No
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception No
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally Yes
F.3.3.6.1Details of subjects incapable of giving consent
Patients of 12 years and older have to coconsent. Parents of patients under 12 years will consent for participation. Additional material to inform subjects about the study is available for all age categories.
Patiënten van 12 jaar of ouder moeten coconsent geven. Voor patiënten onder de 12 jaar zullen ouders toestemming geven voor deelname. Er is additioneel materiaal beschikbaar om kinderen van verschillende leeftijdsgroepen te informeren.
F.3.3.7Others Yes
F.3.3.7.1Details of other specific vulnerable populations
minors
minderjarigen
F.4 Planned number of subjects to be included
F.4.1In the member state132
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)
None. Treatment will be determined by the pediatric rheumatologists at all times of the study and after. The doctor can decide at any time to discontinue study participation and prescribe alternative treatment.
Geen. Behandeling wordt bepaald door de kinderreumatoloog ten alle tijden van en na het onderzoek. De dokter kan op elk moment in de studie besluiten dat deelname stopt en er een alternatieve behandeling gevolgd wordt.
G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2018-05-23
N.Ethics Committee Opinion of the trial application
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion
P. End of Trial
P.End of Trial Status

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner