Clinical trial NCT02440126: Longitudinal Analysis And Sample Collection To Evaluate PML Risk Host Markers for PML Risk Host Markers for PML Risk
Official title: Longitudinal Meta-Analysis and Further Sample Collection To Evaluate Potential Host Markers for PML Risk
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
immunological
biomarkers
observational
Relapsing
Remitting Multiple Sclerosis
Lead sponsor: Rocky Mountain MS Research Group, LLC
Sponsor class: OTHER
Collaborators: name: Biogen
First posted: 2015-05-12
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Up to 200 patients with relapsing forms of multiple sclerosis. All subjects will receive open label natalizumab according to their prescribing physician.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Must be enrolled in the TOUCH Prescribing Program for Tysabri® (natalizumab) prior to informed consent.
3. In the opinion of the Principal Investigator, must be able and willing to comply with all study directions
4. ≥ 18 years of age at the time of informed consent

Exclusion Criteria:

1. In the opinion of the Principal Investigator, subject is unwilling or unable to comply with study directions.
2. 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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Primary outcomes:
measure: Pharmacokinetic (PK) Changes over Time
timeFrame: 12 month
measure: Pharmacodynamic (PD) Changes over Time
timeFrame: 12 month
Secondary outcomes:
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Rocky Mountain MS Research Group
state: Utah
Study officials:
affiliation: Rocky Mountain MS Research Group, LLC
name: John F Foley, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schwab N, Schneider-Hohendorf T, Posevitz V, Breuer J, Gobel K, Windhagen S, Brochet B, Vermersch P, Lebrun-Frenay C, Posevitz-Fejfar A, Capra R, Imberti L, Straeten V, Haas J, Wildemann B, Havla J, Kumpfel T, Meinl I, Niessen K, Goelz S, Kleinschnitz C, Warnke C, Buck D, Gold R, Kieseier BC, Meuth SG, Foley J, Chan A, Brassat D, Wiendl H. L-selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients. Neurology. 2013 Sep 3;81(10):865-71. doi: 10.1212/WNL.0b013e3182a351fb. Epub 2013 Aug 7.