Multiple Sclerosis (MS)Phase 2ATPNCT01710228
Alternative Treatment Paradigm for Natalizumab Trial
A Phase 2 study testing methylprednisolone in people with Multiple Sclerosis (MS), run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
This study is being done to determine the difference between natalizumab therapy followed by two different withdrawal strategies using Glatiramer Acetate (GA) treatment paradigms in preventing clinical relapses and other markers of disease activity in patients diagnosed with Multiple Sclerosis (MS). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis (MS)
- What is being tested?
- methylprednisolone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Dec 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age between 18 and 60 years, inclusive.
- Diagnosis of relapsing forms of MS using revised McDonald Criteria 11.
- Patients who have not failed GA therapy.
- EDSS 0 - 5.5 (Functional system changes in cerebral (or mental) functions and in bowel and bladder functions not used in determining EDSS for protocol eligibility).
- No more than two relapses in the 12 months prior to initiating natalizumab therapy.
- A minimum of 9 doses of natalizumab prior to randomization.
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- Disease controlled under natalizumab treatment demonstrated by the absence of relapses (no relapse in the 9 months prior to randomization)
- Understood and signed written informed consent, obtained prior to the study subject undergoing any study-related procedure, including screening tests.
- Enrollment of patients in the TOUCHTM program at United States of America study sites as long as required: According to guidelines established by the Department of Health \& Human Services, natalizumab is currently only available under a special restricted distribution program called TOUCHTM within the United States
Who cannot join
- Known hypersensitivity to GA.
- Initiation of new immunosuppressant treatment after the subject becomes protocol-eligible (except for corticosteroids) or enrollment in a concurrent trial unless an exception is granted following consideration by the MS Review Panel.
- Patients who were treated with GA before natalizumab therapy and failed GA therapy.
- Subjects with any history of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).
- Active hepatitis B or hepatitis C infection or evidence of cirrhosis.
- HIV positivity.
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- Uncontrolled diabetes mellitus defined as HbA1c > 8% and/or requiring intensive management.
- Uncontrolled viral, fungal, or bacterial infection (excluding asymptomatic bacteriuria).
- Any condition that, in the opinion of the investigators, would jeopardize the ability of the subject to tolerate treatment with GA.
- Prior history of malignancy, except localized basal cell or squamous skin cancer. Other malignancies for which the subject is judged to be cured by the administered therapy, such as head and neck cancer, or breast cancer, will be considered on an individual basis by the Study's MS review panel.
- Positive pregnancy test or inability or unwillingness to use effective means of birth control. Effective birth control is defined as:
- Refraining from all acts of vaginal intercourse (abstinence),
- Consistent use of birth control pills,
- Injectable birth control methods (®Depo-Provera, ®Norplant),
- Tubal sterilization or male partner who has undergone vasectomy,
- Placement of an IUD (intrauterine device)
- Use, with every act of intercourse, of a diaphragm with contraceptive jelly and/or condoms with contraceptive foam.
- Presence of metallic objects implanted in the body that would preclude the ability of the subject to safely have MRI exams.
- Psychiatric illness, mental deficiency, or cognitive dysfunction making compliance with treatment or informed consent impossible.
- -
Trial locations and contacts
1 site in 1 country.
About this study
This study is being done to determine the difference between natalizumab therapy followed by two different withdrawal strategies using Glatiramer Acetate (GA) treatment paradigms in preventing clinical relapses and other markers of disease activity in patients diagnosed with Multiple Sclerosis (MS).
We hypothesize that GA plus corticosteroids versus GA alone will prevent or reduce the re-occurrence of MS disease activity after discontinuation of natalizumab over a 12 month period. We further hypothesize that natalizumab therapy followed by GA treatment allows the reconstitution of the peripheral and CNS immune homeostasis.
Read more
Primary objective:
The primary endpoint will be the annualized relapse rate over the post randomization months as well as estimates of change over the natalizumab therapy period over the entire 12 months.
Secondary objectives:
To determine if and how long it takes for restoration of immune homeostasis under GA therapy following discontinuation of natalizumab.
Read the detailed description
This is a phase IIb, multicenter, double-blinded randomized trial that will determine the effects of two GA treatment paradigms to prevent re-occurrence of disease activity and immunological rebound after withdrawal from natalizumab therapy. Importantly, the results of this trial may apply to other immunoactive agents.
A total of 200 patients with relapsing forms of multiple sclerosis (MS) will be recruited at 20 study sites in the United States and Europe.
Natalizumab at a dose of 300 mg intravenous (i.v.) infusion each month will be given as standard of care for at least 9 months prior to patient being enrolled in the study. One day after the last infusion of natalizumab the patient will start conversion paradigms to Glatiramer Acetate (GA). GA will be administered daily at a subcutaneous (s.c.) dose of 20 mg. On day 1, 2 months after the patient has been on GA therapy, patient will be randomized to be treated with methylprednisolone or methylprednisolone placebo at an oral dose of 192 mg/day po for 5 consecutive days per month for the duration of the study.
Both Natalizumab and Glatiramer Acetate (GA) have been approved by the FDA to treat relapsing remitting multiple sclerosis.
Natalizumab will not be given as a study medication. Part of the inclusion criteria is that patients are already receiving Natalizumab as standard of care.
Natalizumab until randomization will be provided by the patients' medical insurance. Glatiramer acetate (GA) from randomization till the end of the study (for 12 months) will be provided by the patients' medical insurance. Teva Pharmaceuticals is the manufacturer of methylprednisolone and methylprednisolone placebo 24-mg tablets, which will look identical.
Treatment Arms
During a 1 month screening period (month -1), inclusion and exclusion criteria will be verified, and subjects will be enrolled in the GA only portion following registration with the web-based data entry system and at month 3, they will be randomly assigned to treatment that will be stratified according to study site in varying block sizes One day after the last natalizumab infusion (month 0), 200 Patients on natalizumab therapy will be started on GA. On day 1 of month 3, subjects will be randomized 1:1 to receive either:
- Methylprednisolone placebo ("GA \& PL") or
- Methylprednisolone ("GA \& MP") in addition to GA therapy. Randomization to the two treatment arms will occur via a random number generator by a centralized data entry system that checks eligibility prior to initiating randomization to prevent inappropriate inclusions.
Study Endpoints:
- The primary endpoint will be the annualized relapse rate.
- A key secondary endpoint is the percentage of relapse-free patients at 12 months.
- Other secondary outcomes are the rate of early relapse rebound (assessed in all 200 patients prior to randomization), number of new GD+ lesions on MRI over the 12 months treatment period, defined as the period following the first infusion (month 0) to 6 months and 12 months after randomization, annualized relapse rate, and progression of neurological as assessed by changes in EDSS.
- Other MRI outcomes will include the cumulative combined unique activity (CUA) (new or enlarging T2 lesions or enhancing lesions).
- Another secondary endpoint is the percentage of patients who appear to be free of disease activity as measured by clinical relapses, disability progression measured by the Expanded Disability Status Scale EDSS), and the cumulative combined unique activity (CUA) (new or enlarging T2 lesions or enhancing lesions) on MRI at 12 months.
- Conditions
- Multiple Sclerosis (MS)
- Being tested
- methylprednisolone
- Keywords
- MS, Natalizumab, copaxone
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
192 MG FOR 5 CONSECUTIVE DAYS EVERY 4 WEEKS FOR 10 MONTHS
| Study group | Role | What they receive |
|---|---|---|
| Methylprednisolone placebo | Placebo comparator | subjects will be randomized 1:1 to receive either:
1. Methylprednisolone placebo or
2. Methylprednisolone Receives: Drug: methylprednisolone |
| methylprednisolone | Experimental | subjects will be randomized 1:1 to receive either:
1. Methylprednisolone placebo or
2. Methylprednisolone Receives: Drug: methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
annualized relapse rate
The primary endpoint will be the annualized relapse rate over the post randomization months as well as estimates of change over the natalizumab therapy period over the entire 12 months.
Measured: 1 YEAR
Secondary outcomes (1)
restoration of immune homeostasis - evaluated by regular brain MRI with contrast at baseline, month6 and month 12 of the study
To determine if and how long it takes for restoration of immune homeostasis under GA therapy following discontinuation of natalizumab. To determine if and how long it takes for restoration of immune homeostasis under GA therapy following discontinuation of natalizumab. The study will evaluate the cellular composition in peripheral blood in patients with relapsing forms of MS receiving natalizumab followed by GA therapy at 0, 3, 6, 9, and 12 months post treatment conversion. MP or PL will be added at month 3 and the impact of MP on restoration will be assessed by regular brain MRI imaging with contrast
Measured: 1 YEAR
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2012 (estimated)
- Study startJul 2013
- Primary completionDec 2013
- Study completionDec 2013
Why it stopped: sponsor stopped
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Sclerosis (MS)Studies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Teva Branded Pharmaceutical Products R&D, Inc., The University of Texas Health Science Center, Houston, University of Alabama at Birmingham, Charite University, Berlin, Germany
- Responsible party
- Sponsor
- Investigators
- Olaf Stuve, MD PhD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01710228
- Sponsor's protocol ID
- STU092011-077
- Acronym
- ATP
- Status last verified
- Dec 2016
- First submitted
- 4 Sep 2012
- Last updated
- 29 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alternative Treatment Paradigm for Natalizumab Trial
- ClinicalTrials.gov ID
- NCT01710228
- Acronym / sponsor ID
- ATP / STU092011-077
- Conditions
- Multiple Sclerosis (MS)
- Keywords
- MS, Natalizumab, copaxone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: sponsor stopped
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- Teva Branded Pharmaceutical Products R&D, Inc., The University of Texas Health Science Center, Houston, University of Alabama at Birmingham, Charite University, Berlin, Germany
- Study start
- Jul 2013
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 19 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being done to determine the difference between natalizumab therapy followed by two different withdrawal strategies using Glatiramer Acetate (GA) treatment paradigms in preventing clinical relapses and other markers of disease activity in patients diagnosed with Multiple Sclerosis (MS).
We hypothesize that GA plus corticosteroids versus GA alone will prevent or reduce the re-occurrence of MS disease activity after discontinuation of natalizumab over a 12 month period. We further hypothesize that natalizumab therapy followed by GA treatment allows the reconstitution of the peripheral and CNS immune homeostasis.
Primary objective:
The primary endpoint will be the annualized relapse rate over the post randomization months as well as estimates of change over the natalizumab therapy period over the entire 12 months.
Secondary objectives:
To determine if and how long it takes for restoration of immune homeostasis under GA therapy following discontinuation of natalizumab.
Detailed description
This is a phase IIb, multicenter, double-blinded randomized trial that will determine the effects of two GA treatment paradigms to prevent re-occurrence of disease activity and immunological rebound after withdrawal from natalizumab therapy. Importantly, the results of this trial may apply to other immunoactive agents.
A total of 200 patients with relapsing forms of multiple sclerosis (MS) will be recruited at 20 study sites in the United States and Europe.
Natalizumab at a dose of 300 mg intravenous (i.v.) infusion each month will be given as standard of care for at least 9 months prior to patient being enrolled in the study. One day after the last infusion of natalizumab the patient will start conversion paradigms to Glatiramer Acetate (GA). GA will be administered daily at a subcutaneous (s.c.) dose of 20 mg. On day 1, 2 months after the patient has been on GA therapy, patient will be randomized to be treated with methylprednisolone or methylprednisolone placebo at an oral dose of 192 mg/day po for 5 consecutive days per month for the duration of the study.
Both Natalizumab and Glatiramer Acetate (GA) have been approved by the FDA to treat relapsing remitting multiple sclerosis.
Natalizumab will not be given as a study medication. Part of the inclusion criteria is that patients are already receiving Natalizumab as standard of care.
Natalizumab until randomization will be provided by the patients' medical insurance. Glatiramer acetate (GA) from randomization till the end of the study (for 12 months) will be provided by the patients' medical insurance. Teva Pharmaceuticals is the manufacturer of methylprednisolone and methylprednisolone placebo 24-mg tablets, which will look identical.
Treatment Arms
During a 1 month screening period (month -1), inclusion and exclusion criteria will be verified, and subjects will be enrolled in the GA only portion following registration with the web-based data entry system and at month 3, they will be randomly assigned to treatment that will be stratified according to study site in varying block sizes One day after the last natalizumab infusion (month 0), 200 Patients on natalizumab therapy will be started on GA. On day 1 of month 3, subjects will be randomized 1:1 to receive either:
- Methylprednisolone placebo ("GA \& PL") or
- Methylprednisolone ("GA \& MP") in addition to GA therapy. Randomization to the two treatment arms will occur via a random number generator by a centralized data entry system that checks eligibility prior to initiating randomization to prevent inappropriate inclusions.
Study Endpoints:
- The primary endpoint will be the annualized relapse rate.
- A key secondary endpoint is the percentage of relapse-free patients at 12 months.
- Other secondary outcomes are the rate of early relapse rebound (assessed in all 200 patients prior to randomization), number of new GD+ lesions on MRI over the 12 months treatment period, defined as the period following the first infusion (month 0) to 6 months and 12 months after randomization, annualized relapse rate, and progression of neurological as assessed by changes in EDSS.
- Other MRI outcomes will include the cumulative combined unique activity (CUA) (new or enlarging T2 lesions or enhancing lesions).
- Another secondary endpoint is the percentage of patients who appear to be free of disease activity as measured by clinical relapses, disability progression measured by the Expanded Disability Status Scale EDSS), and the cumulative combined unique activity (CUA) (new or enlarging T2 lesions or enhancing lesions) on MRI at 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylprednisolone placebo | Placebo comparator | Drug: methylprednisolonesubjects will be randomized 1:1 to receive either: 1. Methylprednisolone placebo or 2. Methylprednisolone |
| methylprednisolone | Experimental | Drug: methylprednisolonesubjects will be randomized 1:1 to receive either: 1. Methylprednisolone placebo or 2. Methylprednisolone |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Age between 18 and 60 years, inclusive.
- Diagnosis of relapsing forms of MS using revised McDonald Criteria 11.
- Patients who have not failed GA therapy.
- EDSS 0 - 5.5 (Functional system changes in cerebral (or mental) functions and in bowel and bladder functions not used in determining EDSS for protocol eligibility).
- No more than two relapses in the 12 months prior to initiating natalizumab therapy.
Key exclusion criteria (20 listed)
- Known hypersensitivity to GA.
- Initiation of new immunosuppressant treatment after the subject becomes protocol-eligible (except for corticosteroids) or enrollment in a concurrent trial unless an exception is granted following consideration by the MS Review Panel.
- Patients who were treated with GA before natalizumab therapy and failed GA therapy.
- Subjects with any history of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).
- Active hepatitis B or hepatitis C infection or evidence of cirrhosis.
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 |
|---|---|---|
| methylprednisolone192 MG FOR 5 CONSECUTIVE DAYS EVERY 4 WEEKS FOR 10 MONTHS | Drug | Methylprednisolone placebo, methylprednisolone |
Primary outcome
annualized relapse rate
Time frame: 1 YEAR
The primary endpoint will be the annualized relapse rate over the post randomization months as well as estimates of change over the natalizumab therapy period over the entire 12 months.
1 secondary outcome
restoration of immune homeostasis - evaluated by regular brain MRI with contrast at baseline, month6 and month 12 of the study
Time frame: 1 YEAR
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2016.
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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.
Olaf Stuve, MD PhD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing methylprednisolone in people with Multiple Sclerosis (MS), run by University of Texas Southwestern Medical Center at 1 site in United States.
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 9 inclusion and 20 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: withdrawn, as of the sponsor's last update on 29 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
annualized relapse rate (time frame: 1 YEAR). 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 29 Dec 2016.