Longitudinal Analysis And Sample Collection To Evaluate PML Risk Host Markers for PML Risk Host Markers for PML Risk (SRA-001)
17 februari 2021 bijgewerkt door: John F. Foley, MD, Rocky Mountain MS Research Group, LLC
Longitudinal Meta-Analysis and Further Sample Collection To Evaluate Potential Host Markers for PML Risk
The purpose of the study is to develop an improved understanding of the long term pharmacokinetics and pharmacodynamics of natalizumab with both standard dosing and extended dosing, and collect additional samples to explore cell-based biomarkers of natalizumab treatment and PML risk.
Studie Overzicht
Toestand
Voltooid
Conditie
Gedetailleerde beschrijving
The underlying etiology for the association of natalizumab therapy to an increase risk of progressive multifocal leukoencephalopathy (PML) remains unknown.
It is possible that persistently high natalizumab levels lead to sustained immune-modulation or suppression resulting in an increased PML risk.
Since 2010 we have conducted three investigator initiated trials (IITs) at our center to measure serum natalizumab concentration, lymphocyte alpha 4 integrin saturation, and other biomarkers to understand the association of these markers to PML risk.
A number of the patients who participated in these clinical trials are still infusing.
These studies have demonstrated that plasma natalizumab concentrations continue to rise over time with a plateau effect not yet clearly delineated.
Improved drug clearance in patients with higher body weight is described in the prescribing information.
We have accumulated preliminary data suggesting that patients with lower body weight may be at higher risk for PML and that this may relate to higher drug concentrations and saturations seen in this group.
Dose extension may be a viable option to lower drug concentration (pharmacokinetic, PK) and saturation (pharmacodynamic, PD) in patients with lower body weight to potentially impact PML incidence.
In addition to the PK/PD of natalizumab, host related biomarkers may allow for more specific PML risk stratification.
Further validation of these biomarkers is critical for our understanding of their utility.
Studietype
Observationeel
Inschrijving (Werkelijk)
196
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Utah
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Salt Lake City, Utah, Verenigde Staten, 84103
- Rocky Mountain MS Research Group
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Bemonsteringsmethode
Niet-waarschijnlijkheidssteekproef
Studie Bevolking
Up to 200 patients with relapsing forms of multiple sclerosis.
All subjects will receive open label natalizumab according to their prescribing physician.
Beschrijving
Inclusion Criteria:
- Ability to understand the purpose and risks of the study and provide signed and dated consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
- Must be enrolled in the TOUCH Prescribing Program for Tysabri® (natalizumab) prior to informed consent.
- In the opinion of the Principal Investigator, must be able and willing to comply with all study directions
- ≥ 18 years of age at the time of informed consent
Exclusion Criteria:
- In the opinion of the Principal Investigator, subject is unwilling or unable to comply with study directions.
Subject who is pregnant, breastfeeding, or likely to becoming pregnant during the course of the study. Women of child-bearing potential must be practicing an acceptable form of birth control.
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Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Observatiemodellen: Cohort
- Tijdsperspectieven: Ander
Cohorten en interventies
Groep / Cohort |
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Group A: Natalizumab Naïve
This group will consist of up to 10 people who are naïve to natalizumab (haven't received the drug before) and are just beginning therapy.
These participants will meet with the study staff at Week 0 (Baseline) prior to their natalizumab infusion.
They will then have a follow up appointment every 3 months for the first 12 months of their natalizumab infusions, for a total of 5 visits.
Natalizumab concentration and other biomarkers will be measured at each visit.
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Group B: Intracycle Regular Dosing
This group will consist of at least 50 people who are on a regular infusing cycle of 28-31 days.
These participants will be consented at Week 0 (Baseline) and asked to come back each week during their regular cycle at Week 1, Week 2, and Week 3, for a total of 4 study visits.
Natalizumab concentration and other biomarkers will be measured during their participation in the study.
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Group C: Intracycle Extended Dosing
This group will consist of up to 60 people who are on an extended infusing cycle of greater than 30 days.
These participants will be consented at Week 0 (Baseline) and asked to come back each week for a blood draw to measure Natalizumab concentration and other biomarkers during their extended cycle at Week 2, and Week 4, for a total of 3 study visits.
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Group D: Transition Dosing
This group will consist of up to 10 people who are on a regular infusing cycle of 28-30 days who will be transitioning to an extended dosing cycle.
The decision to transition will be made by their treating neurologist.
These participants will be consented at Week 0 (Baseline) and will be followed for 8 cycles.
Natalizumab concentration will be measured at each cycle.
During certain cycles, other biomarkers will be measured.
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Pharmacokinetic (PK) Changes over Time
Tijdsspanne: 12 month
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Changes in natalizumab concentration (ug/ml) will be collected and compared to similar infusion cycle lengths collected previously in investigator-initiated trials at this site.
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12 month
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Pharmacodynamic (PD) Changes over Time
Tijdsspanne: 12 month
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Changes in natalizumab saturation (%) will be collected and compared to similar infusion cycle lengths collected previously in investigator-initiated trials at this site.
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12 month
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Medewerkers
Onderzoekers
- Hoofdonderzoeker: John F Foley, MD, Rocky Mountain MS Research Group, LLC
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start
1 oktober 2014
Primaire voltooiing (Werkelijk)
1 maart 2017
Studie voltooiing (Werkelijk)
1 juli 2020
Studieregistratiedata
Eerst ingediend
16 oktober 2014
Eerst ingediend dat voldeed aan de QC-criteria
6 mei 2015
Eerst geplaatst (Schatting)
12 mei 2015
Updates van studierecords
Laatste update geplaatst (Werkelijk)
21 februari 2021
Laatste update ingediend die voldeed aan QC-criteria
17 februari 2021
Laatst geverifieerd
1 februari 2021
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- SRA-001
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Nee
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