Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Longitudinal Analysis And Sample Collection To Evaluate PML Risk Host Markers for PML Risk Host Markers for PML Risk (SRA-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02440126
Recruitment Status : Recruiting
First Posted : May 12, 2015
Last Update Posted : February 5, 2020
Sponsor:
Collaborator:
Biogen
Information provided by (Responsible Party):
John F. Foley, MD, 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.

Condition or disease
Multiple Sclerosis

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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: Longitudinal Meta-Analysis and Further Sample Collection To Evaluate Potential Host Markers for PML Risk
Study Start Date : October 2014
Actual Primary Completion Date : March 2017
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Group/Cohort
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.
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.
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.
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.



Primary Outcome Measures :
  1. Pharmacokinetic (PK) Changes over Time [ Time Frame: 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.

  2. Pharmacodynamic (PD) Changes over Time [ Time Frame: 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.


Biospecimen Retention:   Samples Without DNA
Serum


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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.

    -


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02440126


Contacts
Layout table for location contacts
Contact: Tammy Hoyt, MS, ACRP 801-408-4584 thoyt@rmmsc.com
Contact: Laura Seawright, BSN, RN 804-408-4584 lseawright@rmmsc.com

Locations
Layout table for location information
United States, Utah
Rocky Mountain MS Research Group Recruiting
Salt Lake City, Utah, United States, 84103
Contact: Tammy Hoyt, MS, CCRC    801-408-5700    thoyt@rmmsc.com   
Principal Investigator: John F Foley, MD         
Sponsors and Collaborators
Rocky Mountain MS Research Group, LLC
Biogen
Investigators
Layout table for investigator information
Principal Investigator: John F Foley, MD Rocky Mountain MS Research Group, LLC
Publications:
Layout table for additonal information
Responsible Party: John F. Foley, MD, President, Sponsor-Investigator, Rocky Mountain MS Research Group, LLC
ClinicalTrials.gov Identifier: NCT02440126    
Other Study ID Numbers: SRA-001
First Posted: May 12, 2015    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by John F. Foley, MD, Rocky Mountain MS Research Group, LLC:
Multiple Sclerosis
immunological
biomarkers
observational
Relapsing
Remitting Multiple Sclerosis
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases