Multiple SclerosisPhase 3PreCISeNCT00666224
Evaluate Early Glatiramer Acetate Treatment in Delaying Conversion to Clinically Definite Multiple Sclerosis of Subjects Presenting With Clinically Isolated Syndrome
A Phase 3 study testing Glatiramer Acetate (DB) and Glatiramer Acetate (OL) in people with Multiple Sclerosis, run by Teva Branded Pharmaceutical Products R&D, Inc..
Trial summary
The primary objective is to assess the effect of treatment with glatiramer acetate (GA) compared to placebo on the time to conversion to CDMS, as determined by Poser criteria (the occurrence of the second clinical attack) during the double-blind period. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Glatiramer Acetate (DB) and Glatiramer Acetate (OL)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 481 participants
- Where
- No sites listed yet
- Study dates
- Jan 2004to Jun 2010
- Phase
- Phase 3
- 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 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- The subject must have undergone a single clinical attack.
- The subject must have a unifocal clinical presentation.
- The subject should be enrolled within the period of 90 days after onset of a single unifocal clinical attack (index attack).
- There must be 2 or more cerebral lesions highly suspicious of multiple sclerosis (MS) on the screening Magnetic Resonance Imaging (MRI), measuring 6mm or more in diameter.
- Subjects must be between the ages of 18 and 45 years inclusive.
- Subjects must not have taken corticosteroids within the 30 days prior to the MRI at the baseline visit.
- Subjects may be male or female. Women of child-bearing potential must practice a medically acceptable method of birth control. Acceptable methods include oral contraceptive, contraceptive patch, long-acting injectable contraceptive, or double-barrier method (condom or intrauterine device with spermicide).
- The subjects must be willing and able to give written informed consent, prior to entering the study.
Who cannot join
- Multifocal clinical presentation.
- Diseases other than MS responsible for the clinical/MRI presentation. The following laboratory tests must be part of the subject's medical history for differential diagnosis of clinically isolated syndrome (CIS): erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), complement (C3, C4) and anticardiolipin IgG - IgM. In the event that the results of these tests are inconclusive, the following additional tests may be requested by the Eligibility Evaluation Committee: syphilis screening, vitamin B12 and folic acid. In the case of spinal cord CIS presentation, a spinal cord MRI is required for confirmation of diagnosis in the medical history of the subject.
- Use of experimental or investigational drugs, including IV immunoglobulin, and/or participation in an investigational drug study within 6 months prior to study entry.
- Use of interferon agents within 6 months prior to the screening visit.
- Chronic corticosteroid treatment (more than 30 consecutive days) in the 6 months prior to study entry.
- Pregnancy or breast feeding.
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- Subjects who experience a relapse between the screening (month -1) and baseline (month 0) visits.
- Life-threatening or other clinically significant disease.
- A medical or psychiatric condition that affects the subject's ability to give informed consent, or to complete the study, or if the subject is considered by the treating neurologist/physician to be, for any other reason, an unsuitable candidate for this study.
- A known history of sensitivity to mannitol.
- A known history of sensitivity to gadolinium.
- Inability to successfully undergo MRI scanning.
About this study
Official title: A Multinational, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Effect of Early Glatiramer Acetate Treatment in Delaying the Conversion to Clinically Definite Multiple Sclerosis (CDMS) of Subjects Presenting With Clinically Isolated Syndrome (CIS)
The primary objective is to assess the effect of treatment with glatiramer acetate (GA) compared to placebo on the time to conversion to CDMS, as determined by Poser criteria (the occurrence of the second clinical attack) during the double-blind period. The secondary objective is to assess, within the time frame of the up to 3-year double-blind, placebo-controlled study period, the effect of GA on clinical and Magnetic Resonance Imaging (MRI) parameters. The long-term objectives of the study (exploratory in nature) are to assess, within the time frame of 5 years, the neuroprotective effect of early versus delayed treatment with GA as reflected by clinical and MRI parameters measuring the accumulated irreversible brain tissue damage.
A pre-planned interim analysis was performed on all efficacy and safety data accumulated in the database up to October 14, 2007, i.e. when 81% of exposure to treatment in the double-blind, placebo-controlled period had been collected. Upon review of the interim analysis results, the Data Monitoring Committee (DMC) recommended that the double-blind portion of the study be stopped and that subjects be switched to the 2-year Open-label period, during which time they would have the option of receiving GA therapy. The sponsor (Teva) adopted the DMC recommendations and took the necessary action towards its implementation.
- Conditions
- Multiple Sclerosis
- Being tested
- Glatiramer Acetate (DB), Placebo, Glatiramer Acetate (OL)
- Keywords
- Clinically Definite Multiple Sclerosis, Clinically Isolated Syndrome, Multiple Sclerosis
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glatiramer Acetate (DB)Drug
Also called Copaxone®
Double blind period (DB): glatiramer acetate (GA) by subcutaneous injection, 20mg, once daily, for up to 36 months or until conversion to clinically definite multiple sclerosis (CDMS).
PlaceboDrug
Double blind period (DB): subcutaneous injection of placebo, once daily, for up to 36 months or until conversion to CDMS
Glatiramer Acetate (OL)Drug
Also called Copaxone®
Open label period (OL): glatiramer acetate (GA), 20 mg, subcutaneous injection, once daily, given for up to an additional 24 months.
| Study group | Role | What they receive |
|---|---|---|
| Glatiramer acetate | Experimental | Glatiramer acetate 20 mg once daily by subcutaneous injection is administered in both the double-blind and open label periods. Receives: Drug: Glatiramer Acetate (DB); Drug: Glatiramer Acetate (OL) |
| Placebo (DB) to GA (OL) | Placebo comparator | Placebo matching glatiramer acetate once daily by subcutaneous injection during the double-blind period (DB). Glatiramer acetate (GA) 20 mg once daily by subcutaneous injection during the open-label period (OL). Receives: Drug: Placebo; Drug: Glatiramer Acetate (OL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion
Data from interim analysis with database lock on October 14, 2007. The time from randomization to conversion to CDMS as determined by the occurrence of a second clinical attack during the double-blind period. Poser criteria are: Two relapses and clinical evidence of two separate lesions; clinical evidence of one lesion and paraclinical evidence of another separate lesion. The two relapses must involve different parts of Central Nervous System and must be separated by a period of at least one month. Lesions are determined by Magnetic Resonance Imaging (MRI).
Measured: up to 3 years
Twenty-fifth Percentile (25%) Kaplan-Meier Estimates for Time From Randomization to Conversion to Clinically Definite Multiple Sclerosis (CDMS) During the Double-blind Period
Data from interim analysis with database lock on October 14, 2007. Due to the number of participants in the glatiramer acetate group that converted to CDMS (see outcome #6), the 25th percentile was considered when running the Kaplan-Meier estimate for time to conversion to CDMS. Conversion to CDMS is determined by the occurrence of the second clinical attack.
Measured: up to 3 years
Secondary outcomes (4)
Number of New T2 Brain Lesions Observed at the Last Observed Value (LOV) in the Double-blind Period
Data from interim analysis with database lock on October 14, 2007. T2 lesions are brain lesions that show on magnetic resonance imaging (MRI) and are associated with multiple sclerosis. This outcome measures the number of new lesions at the last observed value. Last Observed Value (LOV) is defined as the last post baseline measurement taken on study drug but no more than 30 days after study drug cessation.
Measured: up to 3 years
Change From Baseline to Last Observed Value (LOV) in T2 Brain Lesion Volume in the Double-blind Period
Data from interim analysis with database lock on October 14, 2007. The difference in T2 brain lesion volume as observed in MRIs from baseline to the last observed value. Last Observed Value (LOV) is defined as the last post baseline measurement taken on study drug but no more than 30 days after study drug cessation.
Measured: Day 0 (baseline), up to 3 years
Percentage Change in Brain Volume From Baseline to the Last Observed Value (LOV) During the Double-blind Period Using the Structural Image Evaluation of Normalized Atrophy (SIENA) Technique
Data from interim analysis with database lock on October 14, 2007. Brain volume was measured annually by magnetic resonance imaging (MRI) during the Double-blind period. Brain atrophy was measured by comparing the change in brain volume from baseline to the Last Observed Value (LOV). LOV is defined as the last post baseline measurement taken on study drug but no more than 30 days after study drug cessation. SIENA is a fully automated method of analyzing longitudinal brain change.
Measured: Day 0 (baseline), up to 3 years
Percentage of Participants Who Converted to Clinically Definite Multiple Sclerosis (CDMS) During the Double-blind Period
Data from interim analysis with database lock on October 14, 2007. Conversion to CDMS as determined by the occurrence of a second clinical attack during the double-blind period. Poser criteria are: Two relapses and clinical evidence of two separate lesions; clinical evidence of one lesion and paraclinical evidence of another separate lesion. The two relapses must involve different parts of Central Nervous System and must be separated by a period of at least one month. Lesions are determined by Magnetic Resonance Imaging (MRI).
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2008 (estimated)
- Study startJan 2004
- Primary completionOct 2007
- Study completionJun 2010
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 481 participants (actual)
Sponsor and investigators
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00666224
- Sponsor's protocol ID
- GA 9010
- Acronym
- PreCISe
- Status last verified
- Jun 2012
- First submitted
- 22 Apr 2008
- Last updated
- 25 Jun 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Comi G, Martinelli V, Rodegher M, Moiola L, Bajenaru O, Carra A, Elovaara I, Fazekas F, Hartung HP, Hillert J, King J, Komoly S, Lubetzki C, Montalban X, Myhr KM, Ravnborg M, Rieckmann P, Wynn D, Young C, Filippi M; PreCISe study group. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Oct 31;374(9700):1503-11. doi: 10.1016/S0140-6736(09)61259-9. Epub 2009 Oct 6.
PubMed 19815268
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multinational, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Effect of Early Glatiramer Acetate Treatment in Delaying the Conversion to Clinically Definite Multiple Sclerosis (CDMS) of Subjects Presenting With Clinically Isolated Syndrome (CIS)
- ClinicalTrials.gov ID
- NCT00666224
- Acronym / sponsor ID
- PreCISe / GA 9010
- Conditions
- Multiple Sclerosis
- Keywords
- Clinically Definite Multiple Sclerosis, Clinically Isolated Syndrome, Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 481 participants (actual)
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2004
- Primary completion
- Oct 2007 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 24 Apr 2008 (estimated)
- Results
- Posted 13 Jun 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective is to assess the effect of treatment with glatiramer acetate (GA) compared to placebo on the time to conversion to CDMS, as determined by Poser criteria (the occurrence of the second clinical attack) during the double-blind period. The secondary objective is to assess, within the time frame of the up to 3-year double-blind, placebo-controlled study period, the effect of GA on clinical and Magnetic Resonance Imaging (MRI) parameters. The long-term objectives of the study (exploratory in nature) are to assess, within the time frame of 5 years, the neuroprotective effect of early versus delayed treatment with GA as reflected by clinical and MRI parameters measuring the accumulated irreversible brain tissue damage.
A pre-planned interim analysis was performed on all efficacy and safety data accumulated in the database up to October 14, 2007, i.e. when 81% of exposure to treatment in the double-blind, placebo-controlled period had been collected. Upon review of the interim analysis results, the Data Monitoring Committee (DMC) recommended that the double-blind portion of the study be stopped and that subjects be switched to the 2-year Open-label period, during which time they would have the option of receiving GA therapy. The sponsor (Teva) adopted the DMC recommendations and took the necessary action towards its implementation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Glatiramer acetate | Experimental | Drug: Glatiramer Acetate (DB), Drug: Glatiramer Acetate (OL)Glatiramer acetate 20 mg once daily by subcutaneous injection is administered in both the double-blind and open label periods. |
| Placebo (DB) to GA (OL) | Placebo comparator | Drug: Placebo, Drug: Glatiramer Acetate (OL)Placebo matching glatiramer acetate once daily by subcutaneous injection during the double-blind period (DB). Glatiramer acetate (GA) 20 mg once daily by subcutaneous injection during the open-label period (OL). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- The subject must have undergone a single clinical attack.
- The subject must have a unifocal clinical presentation.
- The subject should be enrolled within the period of 90 days after onset of a single unifocal clinical attack (index attack).
- There must be 2 or more cerebral lesions highly suspicious of multiple sclerosis (MS) on the screening Magnetic Resonance Imaging (MRI), measuring 6mm or more in diameter.
- Subjects must be between the ages of 18 and 45 years inclusive.
Key exclusion criteria (12 listed)
- Multifocal clinical presentation.
- Diseases other than MS responsible for the clinical/MRI presentation. The following laboratory tests must be part of the subject's medical history for differential diagnosis of clinically isolated syndrome (CIS): erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), complement (C3, C4) and anticardiolipin IgG - IgM. In the event that the results of these tests are inconclusive, the following additional tests may be requested by the Eligibility Evaluation Committee: syphilis screening, vitamin B12 and folic acid. In the case of spinal cord CIS presentation, a spinal cord MRI is required for confirmation of diagnosis in the medical history of the subject.
- Use of experimental or investigational drugs, including IV immunoglobulin, and/or participation in an investigational drug study within 6 months prior to study entry.
- Use of interferon agents within 6 months prior to the screening visit.
- Chronic corticosteroid treatment (more than 30 consecutive days) in the 6 months prior to study entry.
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 |
|---|---|---|
| Glatiramer Acetate (DB)Also: Copaxone®Double blind period (DB): glatiramer acetate (GA) by subcutaneous injection, 20mg, once daily, for up to 36 months or until conversion to clinically definite multiple sclerosis (CDMS). | Drug | Glatiramer acetate |
| PlaceboDouble blind period (DB): subcutaneous injection of placebo, once daily, for up to 36 months or until conversion to CDMS | Drug | Placebo (DB) to GA (OL) |
| Glatiramer Acetate (OL)Also: Copaxone®Open label period (OL): glatiramer acetate (GA), 20 mg, subcutaneous injection, once daily, given for up to an additional 24 months. | Drug | Glatiramer acetate, Placebo (DB) to GA (OL) |
Primary outcome
Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion
Time frame: up to 3 years
Data from interim analysis with database lock on October 14, 2007. The time from randomization to conversion to CDMS as determined by the occurrence of a second clinical attack during the double-blind period. Poser criteria are: Two relapses and clinical evidence of two separate lesions; clinical evidence of one lesion and paraclinical evidence of another separate lesion. The two relapses must involve different parts of Central Nervous System and must be separated by a period of at least one month. Lesions are determined by Magnetic Resonance Imaging (MRI).
Twenty-fifth Percentile (25%) Kaplan-Meier Estimates for Time From Randomization to Conversion to Clinically Definite Multiple Sclerosis (CDMS) During the Double-blind Period
Time frame: up to 3 years
Data from interim analysis with database lock on October 14, 2007. Due to the number of participants in the glatiramer acetate group that converted to CDMS (see outcome #6), the 25th percentile was considered when running the Kaplan-Meier estimate for time to conversion to CDMS. Conversion to CDMS is determined by the occurrence of the second clinical attack.
4 secondary outcomes
Number of New T2 Brain Lesions Observed at the Last Observed Value (LOV) in the Double-blind Period
Time frame: up to 3 years
Change From Baseline to Last Observed Value (LOV) in T2 Brain Lesion Volume in the Double-blind Period
Time frame: Day 0 (baseline), up to 3 years
Percentage Change in Brain Volume From Baseline to the Last Observed Value (LOV) During the Double-blind Period Using the Structural Image Evaluation of Normalized Atrophy (SIENA) Technique
Time frame: Day 0 (baseline), up to 3 years
Percentage of Participants Who Converted to Clinically Definite Multiple Sclerosis (CDMS) During the Double-blind Period
Time frame: up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19815268Comi G, Martinelli V, Rodegher M, Moiola L, Bajenaru O, Carra A, Elovaara I, Fazekas F, Hartung HP, Hillert J, King J, Komoly S, Lubetzki C, Montalban X, Myhr KM, Ravnborg M, Rieckmann P, Wynn D, Young C, Filippi M; PreCISe study group. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Oct 31;374(9700):1503-11. doi: 10.1016/S0140-6736(09)61259-9. Epub 2009 Oct 6.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Glatiramer Acetate (DB) and Glatiramer Acetate (OL) in people with Multiple Sclerosis, run by Teva Branded Pharmaceutical Products R&D, Inc..
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 8 inclusion and 12 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: finished, as of the sponsor's last update on 25 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Jun 2012). 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 to Clinically Definite Multiple Sclerosis (CDMS) Conversion (time frame: up to 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00666224, which also lists 1 linked publication.
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 25 Jun 2012.