Immune Reconstitution Inflammatory SyndromePhase 4IRISNCT01211665
Corticosteroids for Immune Reconstitution Inflammatory Syndrome (IRIS)
A Phase 4 study testing Methylprednisolone and Prednisolone in people with Immune Reconstitution Inflammatory Syndrome and Leukoencephalopathy, Progressive Multifocal, run by Biogen at 3 sites in 2 countries.
Trial summary
The objectives of this study are to explore the effects of administering high-dose corticosteroids to participants who developed progressive multifocal leukoencephalopathy (PML) while on natalizumab as measured by time-course change in functional status based on Karnofsky Performance Status Index through 6 months… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Immune Reconstitution Inflammatory Syndrome, Leukoencephalopathy, Progressive Multifocal
- What is being tested?
- Methylprednisolone and Prednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Sep 2010to Feb 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have been receiving natalizumab for multiple sclerosis (MS) prior to the diagnosis or suspicion of Progressive multifocal leukoencephalopathy (PML).
- Subject must be willing to undergo or have completed plasma exchange (PLEX) prior to initiating study treatment.
Who cannot join
- History of severe allergic or anaphylactic reactions or known hypersensitivity to any drug including hypersensitivity to corticosteroids.
- NOTE: Other protocol defined inclusion/exclusion criteria may apply.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
About this study
Official title: High-Dose Corticosteroids for Immune Reconstitution Inflammatory Syndrome in Patients Who Develop Progressive Multifocal Leukoencephalopathy on Natalizumab
The objectives of this study are to explore the effects of administering high-dose corticosteroids to participants who developed progressive multifocal leukoencephalopathy (PML) while on natalizumab as measured by time-course change in functional status based on Karnofsky Performance Status Index through 6 months following the completion of plasma exchange (PLEX; or equivalent), survival at 6 months following the completion of PLEX (or equivalent), and incidence and severity of adverse events (AEs) and serious adverse events (SAEs); to characterize the evolution of immune reconstitution inflammatory syndrome (IRIS) as measured by time course changes in Global Clinical Impression of Improvement (GCI-I), Symbol Digit Modalities Test (SDMT), brain magnetic resonance imaging (MRI), magnetoencephalography (MEG), chemokines, cytokines, C-reactive protein (CRP), John Cunningham virus (JCV) load and cell count in cerebrospinal fluid (CSF); and to characterize the time course elimination of serum natalizumab concentrations in the study population following the last PLEX (or equivalent) procedure.
- Being tested
- Methylprednisolone, Prednisolone
- Keywords
- IVMP, corticosteroids, IRIS, Progressive Multifocal Leukoencephalopathy, Immune reconstitution inflammatory syndrome, PML
- Medical subject headings
- Immune Reconstitution Inflammatory Syndrome, Leukoencephalopathy, Progressive Multifocal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Medrol, Solu-Medrol
In intravenous form (for a daily dose of 1 g/day on treatment days).
PrednisoloneDrug
Also called Orapred, Prelone
Oral prednisolone used as a taper, with suggested dosages starting at 80 mg and tapering to 5 mg.
| Study group | Role | What they receive |
|---|---|---|
| Pulsed IVMP | Experimental | Intravenous methylprednisolone (IVMP) 1 g/day administered the first 3 days of each weekly cycle, and repeated for 3 additional cycles (totaling 4 cycles). If necessary, 2 additional weekly cycles of 1 g IVMP daily for 3 days can be administered at the discretion of the investigator. Receives: Drug: Methylprednisolone |
| IVMP with oral prednisolone taper | Experimental | Intravenous methylprednisolone (IVMP) 1g/day for 6 days followed by an oral taper of prednisolone over 2 months (suggested dosages starting at 80 mg and tapering to 5 mg). If necessary, additional cycles of 1 g IVMP daily for 3 to 5 days can be administered at any time. Receives: Drug: Methylprednisolone; Drug: Prednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time Course Change in Functional Status Based on Karnofsky Performance Status Index Through 6 Months Following Completion of Plasma Exchange (PLEX)
The Karnofsky Performance Status Index (KPSI) is an assessment tool intended to assist clinicians and caretakers in gauging a patient's functional status and ability to carry out activities of daily living. A KPSI of 100=normal, no complaints, no evidence of disease; 90=able to carry on normal activity, minor signs or symptoms of disease; 80=normal activity with effort, some signs or symptoms of disease; 70=cares for self, unable to carry on normal activity or do active work; 60=requires occasional assistance but is able to care for most personal needs; 50=requires considerable assistance and frequent medical care; 40=disabled, requires special care and assistance; 30=severely disabled, hospitalization is indicated, although death is not imminent; 20=very sick, hospitalization is necessary, active support treatment is necessary; 10=moribund, fatal processes progressing rapidly; 0=dead.
Measured: Baseline up to 6 months
Number of Participants Who Survived at 6 Months Following Completion of Plasma Exchange (PLEX)
Following the completion of rapid removal of natalizumab using PLEX or equivalent.
Measured: 6 months
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE=any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above.
Measured: from the first dose of study treatment through the end of the treatment period (6 months) + a 4-week post-treatment period
Severity of AEs and SAEs
AEs and SAEs were categorized as mild, moderate or severe according to the following criteria: Mild=barely noticeable to participant or does not make participant uncomfortable; does not influence performance or functioning; prescription drug not ordinarily needed for relief of symptom(s) but may be given because of personality of participant. Moderate=of a sufficient severity to make participant uncomfortable; performance of daily activity is influenced; participant is able to continue in study; treatment for symptom(s) may be needed. Severe=symptoms cause severe discomfort; symptoms cause incapacity or significant impact on participant's daily life; severity may cause cessation of treatment with study treatment; treatment for symptom(s) may be given and/or participant hospitalized. Please see Outcome Measure 3 for AE and SAE definitions.
Measured: from the first dose of study treatment through the end of the treatment period (6 months) + a 4-week post-treatment period
Time Course Change in the Global Clinical Impression of Improvement (GCI-I) Scale
The GCI-I scale is a 7-point scale that assesses how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention, and rates it as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
Measured: Screening to 6 months following completion of PLEX (participants began treatment with intravenous methylprednisolone (IVMP) within 2 weeks after PLEX [or equivalent]).
Time Course Change in Cerebral Dysfunction Using the Symbol Digit Modalities Test (SDMT)
The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution.
Measured: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]).
Time Course Changes in Brain Magnetic Resonance Imaging (MRI)
The brain MRI data collected included: progressive multifocal leukoencephalopathy (PML) lesion localization, T2 hyperintense lesion volume, and signs of cerebral edema.
Measured: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]).
Time Course Change in Magnetoencephalography (MEG) Results
MEG was used to map brain activity.
Measured: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]).
Time Course Change in Clinical Laboratory Values
Clinical laboratory values included chemokines, cytokines, C-reactive protein (CRP), John Cunningham (JC) virus load, and cell count in cerebrospinal fluid.
Measured: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]).
Time Course Elimination of Serum Natalizumab Concentration Following Plasma Exchange (PLEX) or Equivalent
Measured: Baseline up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2010 (estimated)
- Study startSep 2010
- Primary completionFeb 2012
- Study completionFeb 2012
Why it stopped: This study was stopped prematurely due to lack of enrollment within a 1-5-year period.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Immune Reconstitution Inflammatory SyndromeStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Elan Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01211665
- Sponsor's protocol ID
- 101JC404
- Other IDs
- 2010-020369-26
- Acronym
- IRIS
- Status last verified
- Aug 2014
- First submitted
- 29 Jul 2010
- Last updated
- 5 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-Dose Corticosteroids for Immune Reconstitution Inflammatory Syndrome in Patients Who Develop Progressive Multifocal Leukoencephalopathy on Natalizumab
- ClinicalTrials.gov ID
- NCT01211665
- Acronym / sponsor ID
- IRIS / 101JC404
- Keywords
- IVMP, corticosteroids, IRIS, Progressive Multifocal Leukoencephalopathy, Immune reconstitution inflammatory syndrome, PML
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was stopped prematurely due to lack of enrollment within a 1-5-year period.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Collaborators
- Elan Pharmaceuticals
- Study start
- Sep 2010
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 29 Sep 2010 (estimated)
- Results
- Posted 13 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objectives of this study are to explore the effects of administering high-dose corticosteroids to participants who developed progressive multifocal leukoencephalopathy (PML) while on natalizumab as measured by time-course change in functional status based on Karnofsky Performance Status Index through 6 months following the completion of plasma exchange (PLEX; or equivalent), survival at 6 months following the completion of PLEX (or equivalent), and incidence and severity of adverse events (AEs) and serious adverse events (SAEs); to characterize the evolution of immune reconstitution inflammatory syndrome (IRIS) as measured by time course changes in Global Clinical Impression of Improvement (GCI-I), Symbol Digit Modalities Test (SDMT), brain magnetic resonance imaging (MRI), magnetoencephalography (MEG), chemokines, cytokines, C-reactive protein (CRP), John Cunningham virus (JCV) load and cell count in cerebrospinal fluid (CSF); and to characterize the time course elimination of serum natalizumab concentrations in the study population following the last PLEX (or equivalent) procedure.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pulsed IVMP | Experimental | Drug: MethylprednisoloneIntravenous methylprednisolone (IVMP) 1 g/day administered the first 3 days of each weekly cycle, and repeated for 3 additional cycles (totaling 4 cycles). If necessary, 2 additional weekly cycles of 1 g IVMP daily for 3 days can be administered at the discretion of the investigator. |
| IVMP with oral prednisolone taper | Experimental | Drug: Methylprednisolone, Drug: PrednisoloneIntravenous methylprednisolone (IVMP) 1g/day for 6 days followed by an oral taper of prednisolone over 2 months (suggested dosages starting at 80 mg and tapering to 5 mg). If necessary, additional cycles of 1 g IVMP daily for 3 to 5 days can be administered at any time. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Must have been receiving natalizumab for multiple sclerosis (MS) prior to the diagnosis or suspicion of Progressive multifocal leukoencephalopathy (PML).
- Subject must be willing to undergo or have completed plasma exchange (PLEX) prior to initiating study treatment.
Key exclusion criteria (2 listed)
- History of severe allergic or anaphylactic reactions or known hypersensitivity to any drug including hypersensitivity to corticosteroids.
- NOTE: Other protocol defined inclusion/exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethylprednisoloneAlso: Medrol, Solu-MedrolIn intravenous form (for a daily dose of 1 g/day on treatment days). | Drug | IVMP with oral prednisolone taper, Pulsed IVMP |
| PrednisoloneAlso: Orapred, PreloneOral prednisolone used as a taper, with suggested dosages starting at 80 mg and tapering to 5 mg. | Drug | IVMP with oral prednisolone taper |
Primary outcome
Time Course Change in Functional Status Based on Karnofsky Performance Status Index Through 6 Months Following Completion of Plasma Exchange (PLEX)
Time frame: Baseline up to 6 months
The Karnofsky Performance Status Index (KPSI) is an assessment tool intended to assist clinicians and caretakers in gauging a patient's functional status and ability to carry out activities of daily living. A KPSI of 100=normal, no complaints, no evidence of disease; 90=able to carry on normal activity, minor signs or symptoms of disease; 80=normal activity with effort, some signs or symptoms of disease; 70=cares for self, unable to carry on normal activity or do active work; 60=requires occasional assistance but is able to care for most personal needs; 50=requires considerable assistance and frequent medical care; 40=disabled, requires special care and assistance; 30=severely disabled, hospitalization is indicated, although death is not imminent; 20=very sick, hospitalization is necessary, active support treatment is necessary; 10=moribund, fatal processes progressing rapidly; 0=dead.
Number of Participants Who Survived at 6 Months Following Completion of Plasma Exchange (PLEX)
Time frame: 6 months
Following the completion of rapid removal of natalizumab using PLEX or equivalent.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: from the first dose of study treatment through the end of the treatment period (6 months) + a 4-week post-treatment period
AE=any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above.
Severity of AEs and SAEs
Time frame: from the first dose of study treatment through the end of the treatment period (6 months) + a 4-week post-treatment period
AEs and SAEs were categorized as mild, moderate or severe according to the following criteria: Mild=barely noticeable to participant or does not make participant uncomfortable; does not influence performance or functioning; prescription drug not ordinarily needed for relief of symptom(s) but may be given because of personality of participant. Moderate=of a sufficient severity to make participant uncomfortable; performance of daily activity is influenced; participant is able to continue in study; treatment for symptom(s) may be needed. Severe=symptoms cause severe discomfort; symptoms cause incapacity or significant impact on participant's daily life; severity may cause cessation of treatment with study treatment; treatment for symptom(s) may be given and/or participant hospitalized. Please see Outcome Measure 3 for AE and SAE definitions.
Time Course Change in the Global Clinical Impression of Improvement (GCI-I) Scale
Time frame: Screening to 6 months following completion of PLEX (participants began treatment with intravenous methylprednisolone (IVMP) within 2 weeks after PLEX [or equivalent]).
The GCI-I scale is a 7-point scale that assesses how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention, and rates it as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
Time Course Change in Cerebral Dysfunction Using the Symbol Digit Modalities Test (SDMT)
Time frame: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]).
The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution.
Time Course Changes in Brain Magnetic Resonance Imaging (MRI)
Time frame: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]).
The brain MRI data collected included: progressive multifocal leukoencephalopathy (PML) lesion localization, T2 hyperintense lesion volume, and signs of cerebral edema.
Time Course Change in Magnetoencephalography (MEG) Results
Time frame: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]).
MEG was used to map brain activity.
Time Course Change in Clinical Laboratory Values
Time frame: Screening to 6 months following completion of PLEX (participants began treatment with IVMP within 2 weeks after PLEX [or equivalent]).
Clinical laboratory values included chemokines, cytokines, C-reactive protein (CRP), John Cunningham (JC) virus load, and cell count in cerebrospinal fluid.
Time Course Elimination of Serum Natalizumab Concentration Following Plasma Exchange (PLEX) or Equivalent
Time frame: Baseline up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Biogen
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methylprednisolone and Prednisolone in people with Immune Reconstitution Inflammatory Syndrome and Leukoencephalopathy, Progressive Multifocal, run by Biogen at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time Course Change in Functional Status Based on Karnofsky Performance Status Index Through 6 Months Following Completion of Plasma Exchange (PLEX) (time frame: Baseline up to 6 months). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2014.