Natalizumab Temporary Discontinuation Study (NaTDS)
13 mai 2016 mis à jour par: Robert Zivadinov, MD, PhD, University at Buffalo
This study evaluates the discontinuation of natalizumab either immediately or tapered off in the treatment of multiple sclerosis.
Half of the fifty (50) participants will discontinue natalizumab immediately and the other half will taper off the drug, having two additional infusions, one at six weeks- and one at eight weeks-post discontinuation.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
Natalizumab is a pharmaceutical intervention used in the management of multiple sclerosis.
The decision to discontinue natalizumab therapy is often raised in patients defined as high-risk for PML despite good clinical efficacy. During the therapy cessation period following large phase III trials, a return to the prestudy disease activity was reached by four months post-discontinuation. Shorter therapy was associated with a trend for a more severe disease activity pointing to a possible 'rebound' effect after natalizumab discontinuation.
This study focuses on two different approaches: an immediate versus a step-wise/tapered down natalizumab discontinuation protocol, both with reinstitution of a different disease modifying therapy (DMT) within 1-6 months from the last natalizumab infusion.
Type d'étude
Interventionnel
Inscription (Réel)
50
Phase
- Phase 4
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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New York
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Buffalo, New York, États-Unis, 14203
- Buffalo Neuroimaging Analysis Center
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Buffalo, New York, États-Unis, 14203
- Jacobs Neurological Institute
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 65 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Patient with relapsing-remitting or relapsing-progressive (relapsing-remitting with incomplete recovery and secondary progressive with superimposed relapses) MS according to the McDonald criteria who have been on natalizumab therapy for at least 12 months
- Age 18-65
- Have EDSS scores less than or equal to 7.0
- Positive John Cunningham (JC) virus antibody results at screening
- Signed informed consent
- None of the exclusion criteria
Exclusion Criteria:
- Patients not willing or able to personally provide informed consent (subjects with cognitive impairment that effects the ability to provide informed consent for participation)
- Patients with active disease per clinical and MRI evaluation at baseline
- Patients with renal disease that precludes having an MRI with gadolinium contrast
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Soins de soutien
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Seul
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Comparateur actif: Immediate Discontinuation Group
Patients will discontinue the natalizumab therapy at once and initiate another disease modifying therapy at 1 month following the last natalizumab infusion.
The disease modifying therapy at 1 month following natalizumab discontinuation will be at the discretion of the neurologist and may differ among patients.
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Patients will be randomized to one of two groups: The Immediate Discontinuation Group (stop natalizumab immediately and continue with new DMT 1 month afterward) and the Taper-off Group (two additional infusions of natalizumab, one at 6 weeks and the next at 8 weeks following discontinuation.
A new DMT will be initiated within 2 months of final natalizumab infusion).
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Expérimental: Taper-off Group
Patients will be administered two more natalizumab infusion, one at six weeks and the second at eight weeks (14 weeks from study entry), followed by six months natalizumab discontinuation.
Another DMT will be initiated within two months after the last natalizumab infusion.
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Patients will be randomized to one of two groups: The Immediate Discontinuation Group (stop natalizumab immediately and continue with new DMT 1 month afterward) and the Taper-off Group (two additional infusions of natalizumab, one at 6 weeks and the next at 8 weeks following discontinuation.
A new DMT will be initiated within 2 months of final natalizumab infusion).
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Number of recorded infections including viral opportunistic infection
Délai: Up to 1 year follow-up
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Number of recorded infections including viral opportunistic infections (i.e., shingles) will be recorded up to 1-year follow-up; continuous close vigilance will be maintained for possible cases of progressive multifocal leukoencephalopathy (PML)
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Up to 1 year follow-up
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Saturation percentage of α4β1integrin receptors on the surface of lymphocytes
Délai: 12 months
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12 months
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Number gadolinium-enhancing lesions
Délai: Change between baseline-6 months, 6 months-12 months, and baseline-12 months
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Number of gadolinium-enhancing lesions
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Change between baseline-6 months, 6 months-12 months, and baseline-12 months
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Absolute changes in gadolinium-enhancing and T2-weighted lesion volume between timepoints
Délai: Change between baseline-6 months, 6 months-12 months, and baseline-12 months
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Absolute changes in gadolinium-enhancing and T2-weighted lesion volume
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Change between baseline-6 months, 6 months-12 months, and baseline-12 months
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Sum of new and enlarging T2-weighted lesions
Délai: Change between baseline-6 months, 6 months-12 months, and baseline-12 months
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Sum of new and enlarging lesions as seen on T2-weighted images
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Change between baseline-6 months, 6 months-12 months, and baseline-12 months
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Number of clinical relapses
Délai: Either baseline (immediate discontinuation group) or 6 months (taper-off group)
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Number of clinical relapses will be assessed at the time of natalizumab therapy discontinuation which will be different between the two groups
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Either baseline (immediate discontinuation group) or 6 months (taper-off group)
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Expanded Disability Status Scale (EDSS) score
Délai: Either baseline (immediate discontinuation group) or 6 months (taper-off group)
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Expanded disability status scale score
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Either baseline (immediate discontinuation group) or 6 months (taper-off group)
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Chercheur principal: Bianca Weinstock-Guttman, MD, Jacob's Neurological Institute
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 novembre 2012
Achèvement primaire (Réel)
1 mars 2014
Achèvement de l'étude (Réel)
1 mars 2014
Dates d'inscription aux études
Première soumission
29 décembre 2015
Première soumission répondant aux critères de contrôle qualité
13 mai 2016
Première publication (Estimation)
17 mai 2016
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
17 mai 2016
Dernière mise à jour soumise répondant aux critères de contrôle qualité
13 mai 2016
Dernière vérification
1 mai 2016
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- USTYS0910017/JNI-2010-31
Plan pour les données individuelles des participants (IPD)
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