- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica 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
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Queensland
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Brisbane, Queensland, Australia, 4066
- The Wesley-St. Andrew's Research Institute
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South Australia
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Adelaide, South Australia, Australia, 5000
- PARC Clinical Research
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Victoria
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Melbourne, Victoria, Australia, 3004
- Nucleus Network - Centre for Clinical Studies
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Western Australia
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Perth, Western Australia, Australia, 6009
- Western Australian Neuroscience Research Institute
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West Perth, Western Australia, Australia, 6005
- Neurodegenerative Disorders Research
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Auckland, Nuova Zelanda, 1010
- Optimal Clinical Trials
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Wellington, Nuova Zelanda, 6021
- P3 Research
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: 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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Comparatore placebo: Saline
Saline administered i.v.
once weekly for 52 weeks
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Intravenous administration weekly for 52 weeks
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Change from baseline of neuromuscular function at 12 months
Lasso di tempo: 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
Lasso di tempo: 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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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Change from baseline of disability and health status at 12 months
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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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Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Direttore dello studio: Michael Silverman, Innate Immunotherapeutics
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Processi patologici
- Malattie del sistema nervoso
- Malattie del sistema immunitario
- Neoplasie
- Malattie autoimmuni demielinizzanti, SNC
- Malattie autoimmuni del sistema nervoso
- Malattie demielinizzanti
- Malattie autoimmuni
- Processi neoplastici
- Sclerosi multipla
- Sclerosi Multipla Cronica Progressiva
- Sclerosi
- Metastasi neoplastica
Altri numeri di identificazione dello studio
- MIS416-202
- U1111-1166-0910 (Altro identificatore: WHO)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .