- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT02228213
Safety and Efficacy Study of MIS416 to Treat Secondary Progressive Multiple Sclerosis
A Phase 2B Randomised, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of MIS416 in the Treatment of Subjects With Secondary Progressive Multiple Sclerosis
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
The primary objectives of the study are to:
- Determine the efficacy of MIS416, relative to placebo, when administered repeatedly via weekly intravenous (IV) administration to subjects with Secondary Progressive Multiple Sclerosis, as assessed by its effect on measures of neuromuscular function.
- Determine the safety and tolerability of a weekly regimen of MIS416.
The secondary objectives of the study are to:
- Determine the effect of MIS416 on disease activity and neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers including lesions, whole brain atrophy (WBA) and Magnetization Transfer Ratio (MTR).
- Determine the effect of MIS416 on Patient Reported Outcomes (PRO) related to disability and health status.
- Assess, in a subset of subjects, the pharmacodynamic (PD) effects of MIS416, including effects on serum, Peripheral Blood Mononuclear Cell (PBMC), and Cerebral Spinal Fluid (CSF) cytokine/chemokine levels and expression patterns.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
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Queensland
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Brisbane, Queensland, Australie, 4066
- The Wesley-St. Andrew's Research Institute
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South Australia
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Adelaide, South Australia, Australie, 5000
- PARC Clinical Research
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Victoria
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Melbourne, Victoria, Australie, 3004
- Nucleus Network - Centre for Clinical Studies
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Western Australia
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Perth, Western Australia, Australie, 6009
- Western Australian Neuroscience Research Institute
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West Perth, Western Australia, Australie, 6005
- Neurodegenerative Disorders Research
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Auckland, Nouvelle-Zélande, 1010
- Optimal Clinical Trials
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Wellington, Nouvelle-Zélande, 6021
- P3 Research
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- A historical or current cranial MRI scan demonstrating T2-hyperintense lesions consistent with MS.
- Has SPMS as determined by the 2010 Update to the McDonald Criteria
- An Expanded Disability Status Scale (EDSS) of 3.0 to 6.5 at Screening.
- Has SPMS which, in the judgment of the investigator, has been clinically active and functionally progressive within the 2 years prior to Screening
- The absence of MS relapse for at least two years prior to Baseline.
- Neurologically stable for at least four weeks prior to Screening.
Has the following laboratory values within three days prior to initiation of Investigational Product:
- Absolute neutrophil count (ANC) >= 1 x 109/L;
- Platelet count >= 100 x 109/L;
- Serum creatinine =< 1.5 mg/dL;
- Aspartate aminotransferase (AST) =<2 × upper limit of normal;
- Alanine aminotransferase (ALT) =< 2 × upper limit of normal.
- Provided written informed consent to participate.
Exclusion Criteria:
- Has primary Progressive MS (PPMS), Relapsing Remitting (RRMS), or progressive relapsing MS as determined by the 2010 update to the McDonald Criteria.
- Has not completed the discontinuation period for approved and/or investigational multiple sclerosis disease modifying therapies prior to screening.
- Has had any other immunomodulatory drug therapy or immunosuppressive therapy within four weeks prior to Screening, or systemic corticosteroids within the eight weeks prior to Screening.
- Any previous exposure to investigational MS therapeutic vaccines.
- Any use of cell-depleting monoclonal antibodies including, but not limited to, Rituximab, or Ocrelizumab.
- A diagnosis or history of collagen vascular disease (including Sjögren's syndrome and systemic lupus erythematosus), anticardiolipin antibody syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, sarcoidosis, vasculitis, Behcet's syndrome and/or Lyme disease.
- Contraindication to MRI (e.g., pacemaker or other contraindicated implanted metal device, allergy to gadolinium, or unmanageable claustrophobia).
- A history of alcohol or drug abuse (including cannabinoid use) within two years prior to Screening.
- Has had major surgery or radiation therapy within four weeks prior to Screening.
- Has an active infection requiring antibiotics within two weeks prior to Screening.
- Has had active malignancy within two years of Screening, with the exception of basal cell carcinoma and squamous cell carcinoma of the skin.
- Uncontrolled congestive heart failure, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, or transient ischemic attack within twelve weeks prior to Screening.
- Has angina, other symptomatic coronary artery disease, or known cardiomyopathy.
- Has symptomatic cardiac dysrhythmias requiring treatment, or persistent prolongation of the QTcF (Fredericia) interval to > 450 msec for males or > 470 msec for females.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: Treatment
500 mcg MIS416 500 at 0.2 mg/mL administered i.v.
once weekly for 52 weeks
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Intravenous administration weekly for 52 weeks
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Comparateur placebo: Saline
Saline administered i.v.
once weekly for 52 weeks
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Intravenous administration weekly for 52 weeks
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Change from baseline of neuromuscular function at 12 months
Délai: Baseline, 3, 6, 9 and 12 months
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Neuromuscular function will be assessed using the following test:
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Baseline, 3, 6, 9 and 12 months
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Proportion of Participants with Serious and Non-Serious Adverse Events
Délai: Up to 12 months
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Safety assessments will be conducted at each study visit and include; characterization of the type, incidence, severity, timing, seriousness, and relationship to treatment of adverse events (AEs); effects on vital signs and clinical laboratory parameters; changes on electrocardiograms (ECGs); and at 3 months and 12 months - the number of gadolinium-enhancing lesions on cranial MRI assessments.
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Up to 12 months
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Change from baseline of disability and health status at 12 months
Délai: Baseline, 3, 6, 9, and 12 months
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Disability and health status will be assessed using the following assessments and patient reported outcomes:
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Baseline, 3, 6, 9, and 12 months
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Change from baseline of neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers at 12 months
Délai: Baseline, 3, and 12 months
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Disease activity and neurodegeneration will be assessing using Magnetic Resonance Imaging (MRI) markers including lesions, whole brain atrophy (WBA) and Magnetization Transfer Ratio (MTR).
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Baseline, 3, and 12 months
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Change from baseline of activity of immune biomarkers in serum
Délai: Up to 1 year
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The effect on immune biomarkers will include the analysis of serum for some or all of the following markers: IP-10 (CXCL10), MCP-1 (CCL2), MIG (CXCL9), IL-8 (CXCL8), IFNγ, Neopterin, IL-1RA, sTNF-R, IL-12/23, p40, CD62E (E-selectin), CD54 (ICAM-1), and CD106 (VCAM-1).
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Up to 1 year
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Change from baseline of activity of immune biomarkers in cerebrospinal fluid (CSF)
Délai: Up to 12 months
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The effect on immune biomarkers will include the analysis of CSF for some or all of the following markers: IP-10 (CXCL10), MCP-1 (CCL2), MIG (CXCL9), IL-8 (CXCL8), IFNγ, Neopterin, IL-1RA, sTNF-R, IL-12/23, p40, CD62E (E-selectin), CD54 (ICAM-1), and CD106 (VCAM-1).
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Up to 12 months
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Change from baseline in Peripheral Blood Mononuclear Cell (PBMC) immune biomarkers
Délai: Up to 12 months
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Some or all of these biomarkers may be assayed ex vivo: PBMC expression of mRNA encoding proteins involved in myeloid differentiation and immune regulatory function (e.g.
VEGF, Arginine, INOS, IL-10, MMP9); PBMC myeloid subset production of IL-10, TGFβ, IL-6, TNFα, IL-1β, IFNγ, IL-17, and GM-CSF in response to stimulation with LPS, LPS/IFNγ or MIS416 ex vivo; and PBMC subset analysis of myeloid and dendritic cell subsets for immunoregulatory cell subset markers.
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Up to 12 months
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Directeur d'études: Michael Silverman, Innate Immunotherapeutics
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Processus pathologiques
- Maladies du système nerveux
- Maladies du système immunitaire
- Tumeurs
- Maladies auto-immunes démyélinisantes, SNC
- Maladies auto-immunes du système nerveux
- Maladies démyélinisantes
- Maladies auto-immunes
- Processus néoplasiques
- Sclérose en plaques
- Sclérose en plaques, progressive chronique
- Sclérose
- Métastase néoplasmique
Autres numéros d'identification d'étude
- MIS416-202
- U1111-1166-0910 (Autre identifiant: WHO)
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