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

Completed

• Conditions: Multiple Sclerosis

• Registration Number: NCT02440126
• Lead Sponsor: Rocky Mountain MS Research Group, LLC

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.

Study Timeline

• Study Start: 2014-10
• Study First Submitted: 2014-10-16
• Study First Submitted QC: 2015-05-06
• Study First Posted: 2015-05-12
• Primary Completion: 2017-03
• Study Completion: 2020-07
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-17
• Last Update Posted: 2021-02-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 196

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Pharmacodynamic (PD) Changes over Time	12 month	Changes in natalizumab saturation (%) will be collected and compared to similar infusion cycle lengths collected previously in investigator-initiated trials at this site.
Pharmacokinetic (PK) Changes over Time	12 month	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.

Trial Locations

Locations (1)

Rocky Mountain MS Research Group; 🇺🇸 Salt Lake City, Utah, United States