Study to Explore the Effect of Mefloquine in Participants With Progressive Multifocal Leukoencephalopathy (PML)

This study has been terminated.
(Primary endpoint not achieved)
Sponsor:
Collaborator:
Elan Pharmaceuticals
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00746941
First received: September 3, 2008
Last updated: July 2, 2014
Last verified: July 2014
Results First Received: January 3, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single Blind (Outcomes Assessor);   Primary Purpose: Treatment
Condition: Progressive Multifocal Leukoencephalopathy
Intervention: Drug: mefloquine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Twelve sites enrolled participants prior to study termination.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were initially randomized in a 1:1 ratio to the local standard of care arm (represented below as 3 treatment arms depending on Week 4 and Week 8 decisions) or the local standard of care plus mefloquine 250 mg arm.

Reporting Groups
  Description
Local Standard of Care

Participants were randomized to receive local standard of care, which may have included any treatment or procedure that the Investigator would normally use in the treatment of a PML patient at their study site or hospital.

These participants received only local standard of care throughout the study; they did not choose to add 250 mg mefloquine at Week 4 (Day 28) or Week 8 (Day 56).

Local Standard of Care; Mefloquine at Week 4

Participants were randomized to receive local standard of care, which may have included any treatment or procedure that the Investigator would normally use in the treatment of a PML patient at their study site or hospital.

These participants chose to add 250 mg mefloquine by mouth at Week 4 for 3 days and then weekly through Week 24 to their local standard of care treatment.

Local Standard of Care; Mefloquine at Week 8

Participants were randomized to receive local standard of care, which may have included any treatment or procedure that the Investigator would normally use in the treatment of a PML patient at their study site or hospital.

These participants chose to add 250 mg mefloquine by mouth at Week 8 for 3 days and then weekly through Week 24 to their local standard of care treatment.

Local Standard of Care Plus Mefloquine 250 mg Participants were randomized to receive local standard of care (which may have included any treatment or procedure that the Investigator would normally use in the treatment of a PML patient at their study site or hospital) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.

Participant Flow:   Overall Study
    Local Standard of Care     Local Standard of Care; Mefloquine at Week 4     Local Standard of Care; Mefloquine at Week 8     Local Standard of Care Plus Mefloquine 250 mg  
STARTED     7     5     5     20  
COMPLETED     0     1     3     7  
NOT COMPLETED     7     4     2     13  
Death                 2                 0                 0                 6  
Physician Decision                 0                 0                 2                 0  
Withdrawal by Subject                 3                 0                 0                 2  
Other, reason not provided                 2                 4                 0                 4  
Adverse Event                 0                 0                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Local Standard of Care

Participants were randomized to receive local standard of care, which may have included any treatment or procedure that the Investigator would normally use in the treatment of a PML patient at their study site or hospital.

These participants received only local standard of care throughout the study; they did not choose to add 250 mg mefloquine at Week 4 (Day 28) or Week 8 (Day 56).

Local Standard of Care; Mefloquine at Week 4

Participants were randomized to receive local standard of care, which may have included any treatment or procedure that the Investigator would normally use in the treatment of a PML patient at their study site or hospital.

These participants chose to add 250 mg mefloquine by mouth at Week 4 for 3 days and then weekly through Week 24 to their local standard of care treatment.

Local Standard of Care; Mefloquine at Week 8

Participants were randomized to receive local standard of care, which may have included any treatment or procedure that the Investigator would normally use in the treatment of a PML patient at their study site or hospital.

These participants chose to add 250 mg mefloquine by mouth at Week 8 for 3 days and then weekly through Week 24 to their local standard of care treatment.

Local Standard of Care Plus Mefloquine 250 mg Participants were randomized to receive local standard of care (which may have included any treatment or procedure that the Investigator would normally use in the treatment of a PML patient at their study site or hospital) and 250 mg mefloquine by mouth on Days 0, 1, and 2 and then weekly through Week 24.
Total Total of all reporting groups

Baseline Measures
    Local Standard of Care     Local Standard of Care; Mefloquine at Week 4     Local Standard of Care; Mefloquine at Week 8     Local Standard of Care Plus Mefloquine 250 mg     Total  
Number of Participants  
[units: participants]
  7     5     5     20     37  
Age  
[units: years]
Mean ± Standard Deviation
  48.7  ± 20.56     41.6  ± 11.37     47.4  ± 10.06     48.1  ± 9.4     47.2  ± 12.16  
Gender  
[units: participants]
         
Female     1     2     2     5     10  
Male     6     3     3     15     27  
Race (NIH/OMB)  
[units: participants]
         
American Indian or Alaska Native     0     0     0     0     0  
Asian     0     0     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0     0     0  
Black or African American     1     2     2     4     9  
White     6     3     3     16     28  
More than one race     0     0     0     0     0  
Unknown or Not Reported     0     0     0     0     0  
Disease history [1]
[units: participants]
         
HIV positive: HAART Naive     3     5     3     13     24  
HIV positive: History of HAART     1     0     1     3     5  
HIV negative     3     0     1     4     8  
JVC Titer at Screening [2]
[units: participants]
         
<= 50 copies/mL     0     0     0     4     4  
> 50 copies/mL     7     5     5     15     32  
Missing     0     0     0     1     1  
[1]

Participants were stratified into the following groups

  • HAART-naïve stratum: human immunodeficiency virus (HIV) -positive participants who developed PML in the absence of highly active anti-retroviral therapy (HAART) were placed in this stratum.
  • History of HAART stratum: HIV-positive participants who developed PML while on HAART were placed in this stratum.
  • HIV-negative stratum: All participants who were HIV-negative were placed in this stratum.
[2] JC virus (human polyomavirus) titer prior to study randomization.



  Outcome Measures
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1.  Primary:   Change From Baseline to Week 4 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF)   [ Time Frame: Day 0 (baseline), Week 4 ]

2.  Primary:   Change From Baseline to Week 8 in JC Virus (JCV) Load in Cerebrospinal Fluid (CSF)   [ Time Frame: Day 0 (baseline), Week 8 ]

3.  Secondary:   Change From Baseline to Week 4 and Week 8 in the Expanded Disability Status Scale (EDSS) Score   [ Time Frame: Day 0 (baseline), Week 4 and 8 ]

4.  Secondary:   Change From Baseline to Week 4 and Week 8 in Karnofsky Performance Status (KPS) Index Score   [ Time Frame: Day 0 (baseline), Week 4, Week 8 ]

5.  Secondary:   Change From Baseline to Week 4 and Week 8 in Symbol Digit Modalities Test (SDMT)   [ Time Frame: Day 0 (baseline), Week 4, Week 8 ]

6.  Secondary:   Change From Baseline to Week 4 and Week 8 in Participants' Neurological Function Using a Visual Analog Scale (VAS)   [ Time Frame: Day 0 (baseline), Week 4, Week 8 ]

7.  Secondary:   Participants With Gadolinium (Gd)-Enhanced Lesions at Baseline, Week 4 and Week 8 as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains   [ Time Frame: Day 0 (baseline), Week 4, Week 8 ]

8.  Secondary:   Change From Baseline to Week 4 and Week 8 in T1 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains   [ Time Frame: Day 0 (baseline), Week 4, Week 8 ]

9.  Secondary:   Change From Baseline to Week 4 and Week 8 in T2 Lesion Volume as Seen on Magnetic Resonance Imaging (MRI) Scans of Participants' Brains   [ Time Frame: Day 0 (baseline), Week 4, Week 8 ]

10.  Secondary:   Participants Who Died Within 6 Months   [ Time Frame: Day 1 up to 6 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
From ongoing analysis, it became clear, based on conditional power calculations, that the study would not reach its primary endpoint, a decrease of JC viral load in CSF with mefloquine treatment; therefore, the study was terminated early.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Biogen Idec Study Medical Director
Organization: Biogen Idec
e-mail: clinicaltrials@biogenidec.com


Publications of Results:

Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT00746941     History of Changes
Other Study ID Numbers: 111JC101
Study First Received: September 3, 2008
Results First Received: January 3, 2013
Last Updated: July 2, 2014
Health Authority: Brazil: National Health Surveillance Agency
Italy: Ministry of Health
Spain: Spanish Agency of Medicines
Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration