E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic inflammatory demyelinating polyneuropathy (CIDP) |
Chronische inflammatoïre demyeliniserende polyneuropathie (CIDP) |
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E.1.1.1 | Medical condition in easily understood language |
Chronic inflammatory demyelinating neuropathy (CIDP) is a disorder of the peripheral nerves which leads to loss of muscle strength and / or sensory loss in the arms and legs |
Chronische inflammatoïre demyeliniserende polyneuropathie (CIDP) is een zenuwontsteking van de perifere zenuwen resulterend in krachtverlies en/of gevoelsstoornissen aan armen en benen. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective of this randomized controlled trial is to assess whether combining IVIg and IVMP leads to more frequent long-term remission in CIDP compared to treatment with IVIg alone. |
Het doel van dit onderzoek is om te bestuderen of het toevoegen van methylprednisolon aan de standaard behandeling met intraveneuze immunoglobulines (IVIg) tot een betere uitkomst leidt dan het gebruik van IVIg alleen. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to explore whether this leads to a higher and faster rate of improvement and whether this combination reduces CIDP associated health care costs en increases quality of life. |
Secundaire doelstelling is om te bepalen of er sneller en betere klinische verbetering optreedt en of deze behandelcombinatie CIPD gerelateerde zorgkosten verlaagd en kwaliteit van leven verbeterd. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion of patients is based on the presence of active disease and fulfillment of the probable or definite EFNS/PNS criteria for CIDP. All new and untreated adult patients are eligible for the study. In addition we will include CIDP patients, treated previously, who have a disease relapse after a remission of at least 1 year, and patients who have responded to their first course of IVIg in the last three months but deteriorated afterwards. |
Patiënten worden geincludeerd als wordt voldaan aan de EFNS/PNS criteria van zeker ('definite') of waarschijnlijk (' probable') CIPD. Alle nieuwe en onbehandelde patiënten komen in aanmerking voor de studie. Ook reeds behandelde CIPD patiënten komen in aanmerking, indien zij een tenminste een jaar in remissie zijn geweest. Ook patiënten die in de laatste 3 maanden klinisch zijn verbeterd na hun eerste IVIg kuur, maar daarna verslechterden, komen in aanmerking. |
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E.4 | Principal exclusion criteria |
1) Presence of IgM paraproteinemia , anti-MAG antibodies or CIDP specific antibodies associated with poor treatment response to IVIg 2) Use of drugs associated with a demyelinating neuropathy 3) Use of any immunosuppressive or immunomodulatory drugs in previous 6 months (except for a single loading dose of IVIg within 3 months), with the exception of low dose prednisone (20 mg or less for the duration of two weeks). 4) Known serious adverse events with previous IVIg or corticosteroid treatment 5) One of more of the risk factors associated with increased risk of adverse events of IVIg or IVMP or conditions that could lead to unblinding of treatment (i.e. diabetes; IgA deficiency; gastric ulcers; psychosis; severe hypertension (180/110 mmHg or more on repeated measurements); hypocalcaemia (lower than 2.20 mmol/L, corrected for albumin); moderate or severe heart failure; severe cardiovascular disease (i.e. more than one myocardial infarction and or ischemic stroke); renal failure (glomerulal filtratrion rate < 30 ml/min) 6) History of osteoporosis or osteoporotic fractures 7) Known malignancy with survival expectancy of less than 1 year 8) Bodyweight more than 120 kg 9) Pregnancy or nursing mother; intention to become pregnant during the course of the study; female patients of childbearing potential either not using or not willing to use a medically reliable method of contraception for the entire duration of the study 10) Cataract 11) Psychosis 12) Poor dental status 13) Legally incompetent adults 14) Lack of written informed consent
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1) aanwezigheid van IgM paraproteinemie, anti-MAG antilichamen en CIDP specifieke antilichamen (geassocieerd met een slechte response op behandeling met IVIg) 2) Gebruik van geneesmiddelen die geassocieerd zijn met (het ontstaan van) demyeliniserende polyneuropathieen 3) Gebruik van immunosuppresieve geneesmiddelen in de afgelopen 6 maanden, met uitzondering van een (enkele) oplaaddosis IVIg in de laatste 3 maanden en een lage dosis prednison (< 20 mg) gedurende 2 weken. 4) Bekende allergische reactie of ernstige bijwerkingen na eerdere behandeling met IVIg of corticosteroiden 5) Een of meerdere risicofactoren geassocieerd met een verhoogde kans op 'adverse events' vanwege IVIg en/of IVMP gebruik, of factoren die op zichzelf kunnen leiden tot deblindering: diabetes mellitus, IgA deficientie, ulcus pepticum, psychose, ernstige hypertensie (180/110 mmHg of hoger, op herhaalde metingen), hypocalciemie (lager dan 2.20, gecorrigeerd voor serum albumine), matig tot ernstig hartfalen, ernstig cardiovasculair lijden ( 1 of meer hartinfarcten of herseninfarcten), nierfalen (eGFR < 30 ml). 6) Voorgeschiedenis bekend met osteoporose of osteoporotische fracturen 7) Bekende maligniteit met een levensverwachting van < 1 jaar 8) Gewicht > 120 kg 9) Zwangerschap of het geven van borstvoeding; actieve zwangerschapswens tijdens duur studie; vrouwen die geen betrouwbare anticonceptie gebruiken of willen gebruiken gedurende de studie periode. 10) Staar/ cataract 11) Psychose 12) Slechte staat van het gebit 13) Wilsonbekwame volwassenen 14) Ontbreken van (ondertekende) informed consent |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome is the number of patients in remission at 1 year after start of an 18 weeks treatment period. Remission is defined as sustained improvement without the need for further treatment. Improvement is defined as improvement by at least the minimal clinical important difference (MCID) on the I-RODS and/or improvement of one or more points on the INCAT disability scale at 18 weeks compared to baseline. Sustained is defined as no deterioration between 18 weeks and 52 weeks, i.e. difference on the I-RODS of less than the individual MCID difference and one or more points on the INCAT disability scale. Patients will be considered as a treatment failure if they 1) receive additional CIDP treatment during the 18-week intervention period, 2) do not improve at 18 weeks, 3) restart CIDP treatment for any reason between 18 and 52 weeks, or 4) do not show a sustained improvement at 52 weeks as defined above. |
Aantal patiënten in remissie, 1 jaar na start van de behandeling. Remissie is gedefineerd als een stabiel ziektebeloop zonder noodzaak tot verdere behandeling. Klinisch verbetering is gedefinieerd als verbetering van invaliditeit (MCID) op de iRODS vragenlijst en/of verbetering van 1 of meer punten op de INCAT disability scale. Patiënten worden gerekend tot 'treatment failure' als 1) er opnieuw behandeld moet worden in de eerste 18 weken, 2) er geen verbetering heeft opgetreden in de eerste 18 weken, 3) er opnieuw behandeling moet worden gestart tussen 18 en 52 weken, 4) als er geen sprake is van een remissie na 52 weken. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary endpoint will be evaluated at 52 weeks. |
Primaire uitkomst wordt op 52 bepaald. |
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E.5.2 | Secondary end point(s) |
1) The number of patients with improvement on disability equal or more than the MCID; 2) Time to improvement (≥ MCID) on disability; 3) Mean change in disability; 4) Mean change in grip strength; 5) Mean change in muscle strength; 6) Mean change in sensory impairment (INCAT SS); 7) Mean change in fatigue; 8) Mean change in pain; 9) Mean change in health related quality of life (HRQL); 10) Number of (serious) adverse events (including corticosteroid associated adverse events); 11) Care use and overall healthcare-related costs;
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1) Het aantal patiënten met verbetering van hun invaliditeit (meer dan de MCID); 2) Tijd tot verbetering (≥ MCID) invaliditeit; 3) Gemiddelde verandering in invaliditeit; 4) Gemiddelde verandering knijpkracht; 5) Gemiddelde verandering spierkracht; 6) Gemiddelde verandering sensibele beperkingen (INCAT SS); 7) Gemiddelde verandering met betrekking tot vermoeidheid; 8) Gemiddelde verandering met betrekking tot pijnklachten; 9) Gemiddelde verandering kwaliteit van leven (HRQL); 10) Aantal bijwerkingen: (serious) adverse events, (S)AEs; 11) Zorggebruik en algemene zorg gerelateerde kosten;
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 18 and 52 weeks. Measuring of these parameters is done consistently (table 1 and 2 in the study protocol, version 4.4.) in the intervention and follow up period. Main secondary outcomes are evaluated at 18 and 52 weeks. Secondary outcomes are also determined according to follow-up protocol (the schedule of which is refered to previously) in case an early endpoint is reached. |
op 18 en 52 weken. Deze parameters worden frequent gemeten (tabel 1 en 2 van het protocol, versie 4.4.). Secundaire uitkomstmaten worden primair geëvalueerd op 18 en 52 weken. Het follow-up protocol en het meten van secundaire uitkomstmaten verloopt volgens het eerder genoemde schema, ook als een vroege eindpunt wordt gehaald. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial 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
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Last day of follow up for last included patient |
Na het einde van de follow up voor de laatst geincludeerde patient |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |