Longitudinal Analysis And Sample Collection To Evaluate PML Risk Host Markers for PML Risk Host Markers for PML Risk

Multiple Sclerosis Clinical Trial

— SRA-001  

Official title:

Longitudinal Meta-Analysis and Further Sample Collection To Evaluate Potential Host Markers for PML Risk

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02440126
• Other study ID #: SRA-001
• Status: Completed
• Start date: October 2014
• Est. completion date: July 2020

Study information

• Verified date: February 2021
• Source: Rocky Mountain MS Research Group, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: July 2020
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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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Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Locations

Country	Name	City	State
United States	Rocky Mountain MS Research Group	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Rocky Mountain MS Research Group, LLC	Biogen

Country where clinical trial is conducted

United States, 

References & Publications (1)

Schwab N, Schneider-Hohendorf T, Posevitz V, Breuer J, Göbel K, Windhagen S, Brochet B, Vermersch P, Lebrun-Frenay C, Posevitz-Fejfár A, Capra R, Imberti L, Straeten V, Haas J, Wildemann B, Havla J, Kümpfel 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic (PK) Changes over Time	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.	12 month
Primary	Pharmacodynamic (PD) Changes over Time	Changes in natalizumab saturation (%) will be collected and compared to similar infusion cycle lengths collected previously in investigator-initiated trials at this site.	12 month