Relapsing-Remitting Multiple SclerosisPhase 1NCT00559702
Safety Study of Natalizumab to Treat Multiple Sclerosis (MS)
A Phase 1 study testing natalizumab in people with Relapsing-Remitting Multiple Sclerosis and Secondary Progressive Multiple Sclerosis, run by Biogen at 12 sites in United States.
Trial summary
The primary objective of this study is to compare the pharmacokinetic (PK) and pharmacodynamics (PD) of single subcutaneous (SC) and intramuscular (IM) doses of 300 mg natalizumab to intravenous (IV) administration of 300 mg natalizumab in multiple sclerosis (MS) participants. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Relapsing-Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis
- What is being tested?
- natalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 12 sitesUnited States
- Study dates
- Oct 2007to Nov 2011
- Phase
- Phase 1
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For arms 1,2,3 and 4: Diagnosis of Secondary Progressive Multiple Sclerosis (SPMS)
- For arms 5 and 6: Diagnosis of relapsing forms of Multiple Sclerosis (MS).
- No past history of receiving natalizumab.
Who cannot join
- For arms 1,2,3 and 4 Diagnosis of primary progressive MS or relapsing-remitting MS.
- Form arms 5 and 6: Diagnosis of primary progressive MS or secondary progressive MS without the occurrence of relapses.
- NOTE: Other protocol defined inclusion/exclusion criteria may apply.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Research Site
Berkeley, California, 94705
Research Site
Buffalo, New York, 14203
Research Site
Centennial, Colorado, 80112
Research Site
Dallas, Texas, 75214
Research Site
Farmington Hills, Michigan, 48334
Research Site
Maitland, Florida, 32751
Research Site
Peoria, Illinois, 61637
Research Site
Phoenix, Arizona, 85006
Research Site
Round Rock, Texas, 78681
Research Site
Scottsdale, Arizona, 85259
Research Site
Vero Beach, Florida, 32960
Research Site
Vienna, Virginia, 22182
About this study
Official title: A Randomized, Open-Label, Dose-Ranging Study to Evaluate the Pharmacokinetics and Initial Safety of Subcutaneous and Intramuscular Natalizumab in Subjects With Multiple Sclerosis
The primary objective of this study is to compare the pharmacokinetic (PK) and pharmacodynamics (PD) of single subcutaneous (SC) and intramuscular (IM) doses of 300 mg natalizumab to intravenous (IV) administration of 300 mg natalizumab in multiple sclerosis (MS) participants. The secondary objectives are to investigate the safety, tolerability and PK of repeated natalizumab doses administered SC and IM, to investigate the immunogenicity of repeated natalizumab doses administered SC and IM, to explore proof of concept within the secondary progressive multiple sclerosis (SPMS) population using change from baseline in clinical measures including: expanded disability status scale (EDSS), multiple sclerosis functional composite scale (MSFC), symbol digit modalities test (SDMT), visual analogue scale (VAS), and visual function test; and brain magnetic resonance imaging (MRI) measures including: number of new or newly-enlarging T2 hyperintense lesions, number of new T1 hypointense lesions, number of new gadolinium-enhancing (Gd+) lesions, whole brain atrophy, magnetization transfer ratio (MTR), and diffusion tensor imaging (DTI) and to observe the effect of natalizumab administered IV and SC on brain MRI measures in participants with relapsing forms of MS.
- Being tested
- natalizumab, standard of care
- Keywords
- natalizumab, multiple sclerosis, Tysabri ®
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
natalizumabDrug
Also called Tysabri ®, BG00002
natalizumab
standard of careOther
standard of care as determined by the Investigator and Treating Neurologist
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Natalizumab IV (Participants with secondary progressive multiple sclerosis) Receives: Drug: natalizumab |
| 2 | Experimental | Natalizumab IM (Participants with secondary progressive multiple sclerosis) Receives: Drug: natalizumab |
| 3 | Experimental | Natalizumab SC (Participants with secondary progressive multiple sclerosis) Receives: Drug: natalizumab |
| 4 | Other | Standard of care as determined by the Investigator and Treating Neurologist (Participants with secondary progressive multiple sclerosis) Receives: Other: standard of care |
| 5 | Experimental | Natalizumab SC (Participants with relapsing forms of multiple sclerosis) Receives: Drug: natalizumab |
| 6 | Experimental | Natalizumab IV (Participants with relapsing forms of multiple sclerosis) Receives: Drug: natalizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed concentration (Cmax) of natalizumab
Measured: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Time to maximum observed concentration (Tmax) of natalizumab
Measured: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Area under the curve to the last measurable concentration (AUC0-last) of natalizumab
Area under the curve to the last measurable concentration as measured by the trapezoidal rule.
Measured: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Apparent volume of distribution of natalizumab
Measured: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Half-life of natalizumab
Measured: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Area under the curve extrapolated to infinity (AUC0-∞) of natalizumab
Measured: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Apparent Clearance of natalizumab
Measured: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
α4-integrin saturation
PD activity will be assessed by measuring the degree of natalizumab saturation of the very late antigen-4 (also known as α4β1 integrin) VLA-4 (α4β1) receptor on peripheral blood lymphocyte/monocyte populations.
Measured: Pre-dose, 4, 24 and 72 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Secondary outcomes (17)
Number of Participants with adverse events
Measured: 13-19 months
Number of participants with abnormalities in vital signs
Measured: 13-19 months
Number of participants with changes in the physical examination
Measured: 13-19 months
Number of participants with abnormal laboratory test results
Measured: 13-19 months
Number of participants with natalizumab antibodies
Measured: Days 28, 42, 56, Weeks 24 and 32
Change from Baseline in expanded disability status scale (EDSS)
The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.
Measured: Baseline, Weeks 8, 20, and 32
Change form Baseline in Multiple Sclerosis Functional Composite Scale (MFSC)
The MFSC consists of 3 tests: 1. Timed 25-Foot Walk, a quantitative mobility and leg function performance test where the participant is timed while walking for 25 feet; 2. 9-Hole Peg Test (9HPT), a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. 3. 3 Second Paced Auditory Serial Addition Test (PASAT 3). The MSFC is based on the concept that scores for these 3 dimensions - arm, leg, and cognitive function are combined to create a single score that can be used to detect change over time. A composite z-score is created, which represents the number of standard deviations (SDs) a participant's test result is higher (z > 0) or lower (z < 0) than the average test result (z = 0) of the reference population.
Measured: Baseline, Weeks 8, 20, and 32
Change from Baseline in Symbol Digit Modalities Test (SDMT)
SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best).
Measured: Baseline, Weeks 8, 20, and 32
Change from Baseline in visual analog scale (VAS)
The participant's global assessment of well-being as assessed using a visual analogue scale (VAS) is a quality of life measurement that will be evaluated for the specified time periods. Participants report how they feel on a scale of 0 to 100, where 0 indicates being "poor" and 100 being "excellent."
Measured: Baseline, Weeks 8, 20, and 32
Change from Baseline in visual function test
Measured: Baseline, Weeks 8, 20, and 32
Number of new or newly enlarging T2 hyperintense lesions
Measured by magnetic resonance imaging (MRI).
Measured: Baseline and Week 32
Number of new gadolinium-enhanced lesions
Measured by magnetic resonance imaging (MRI).
Measured: Baseline and Week 32
Number of new T1 hypointense lesions
Measured by magnetic resonance imaging (MRI).
Measured: Baseline and Week 32
Whole brain atrophy
Atrophy will be measured as the percent brain volume change (PBVC) and will be assessed using the Structural Image Evaluation of Normalized Atrophy (SIENA).
Measured: Baseline and Week 32
Percent change in magnetization transfer ratio (MTR)
Remyelination will be measured using magnetization transfer ratio (MTR) in whole brain (WB) and normal-appearing brain tissue (NABT),
Measured: Baseline and Week 32
Diffusion tensor imaging (DTI)
Measured: Baseline and Week 32
Injection site pain assessment
Measured: Pre-dose, 5 and 15 minutes and 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2007 (estimated)
- Study startOct 2007
- Primary completionNov 2011
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsing-Remitting Multiple SclerosisStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 76 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
- NCT00559702
- Sponsor's protocol ID
- 101MS102
- Status last verified
- Sep 2014
- First submitted
- 7 Nov 2007
- Last updated
- 9 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label, Dose-Ranging Study to Evaluate the Pharmacokinetics and Initial Safety of Subcutaneous and Intramuscular Natalizumab in Subjects With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT00559702
- Acronym / sponsor ID
- 101MS102
- Keywords
- natalizumab, multiple sclerosis, Tysabri ®
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Collaborators
- Elan Pharmaceuticals
- Study start
- Oct 2007
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 16 Nov 2007 (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.
The primary objective of this study is to compare the pharmacokinetic (PK) and pharmacodynamics (PD) of single subcutaneous (SC) and intramuscular (IM) doses of 300 mg natalizumab to intravenous (IV) administration of 300 mg natalizumab in multiple sclerosis (MS) participants. The secondary objectives are to investigate the safety, tolerability and PK of repeated natalizumab doses administered SC and IM, to investigate the immunogenicity of repeated natalizumab doses administered SC and IM, to explore proof of concept within the secondary progressive multiple sclerosis (SPMS) population using change from baseline in clinical measures including: expanded disability status scale (EDSS), multiple sclerosis functional composite scale (MSFC), symbol digit modalities test (SDMT), visual analogue scale (VAS), and visual function test; and brain magnetic resonance imaging (MRI) measures including: number of new or newly-enlarging T2 hyperintense lesions, number of new T1 hypointense lesions, number of new gadolinium-enhancing (Gd+) lesions, whole brain atrophy, magnetization transfer ratio (MTR), and diffusion tensor imaging (DTI) and to observe the effect of natalizumab administered IV and SC on brain MRI measures in participants with relapsing forms of MS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: natalizumabNatalizumab IV (Participants with secondary progressive multiple sclerosis) |
| 2 | Experimental | Drug: natalizumabNatalizumab IM (Participants with secondary progressive multiple sclerosis) |
| 3 | Experimental | Drug: natalizumabNatalizumab SC (Participants with secondary progressive multiple sclerosis) |
| 4 | Other | Other: standard of careStandard of care as determined by the Investigator and Treating Neurologist (Participants with secondary progressive multiple sclerosis) |
| 5 | Experimental | Drug: natalizumabNatalizumab SC (Participants with relapsing forms of multiple sclerosis) |
| 6 | Experimental | Drug: natalizumabNatalizumab IV (Participants with relapsing forms of multiple sclerosis) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- For arms 1,2,3 and 4: Diagnosis of Secondary Progressive Multiple Sclerosis (SPMS)
- For arms 5 and 6: Diagnosis of relapsing forms of Multiple Sclerosis (MS).
- No past history of receiving natalizumab.
Key exclusion criteria (3 listed)
- For arms 1,2,3 and 4 Diagnosis of primary progressive MS or relapsing-remitting MS.
- Form arms 5 and 6: Diagnosis of primary progressive MS or secondary progressive MS without the occurrence of relapses.
- 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 |
|---|---|---|
| natalizumabAlso: Tysabri ®, BG00002natalizumab | Drug | 1, 2, 3, 5, 6 |
| standard of carestandard of care as determined by the Investigator and Treating Neurologist | Other | 4 |
Primary outcome
Maximum observed concentration (Cmax) of natalizumab
Time frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Time to maximum observed concentration (Tmax) of natalizumab
Time frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Area under the curve to the last measurable concentration (AUC0-last) of natalizumab
Time frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Area under the curve to the last measurable concentration as measured by the trapezoidal rule.
Apparent volume of distribution of natalizumab
Time frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Half-life of natalizumab
Time frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Area under the curve extrapolated to infinity (AUC0-∞) of natalizumab
Time frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Apparent Clearance of natalizumab
Time frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
α4-integrin saturation
Time frame: Pre-dose, 4, 24 and 72 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
PD activity will be assessed by measuring the degree of natalizumab saturation of the very late antigen-4 (also known as α4β1 integrin) VLA-4 (α4β1) receptor on peripheral blood lymphocyte/monocyte populations.
17 secondary outcomes
Number of Participants with adverse events
Time frame: 13-19 months
Number of participants with abnormalities in vital signs
Time frame: 13-19 months
Number of participants with changes in the physical examination
Time frame: 13-19 months
Number of participants with abnormal laboratory test results
Time frame: 13-19 months
Number of participants with natalizumab antibodies
Time frame: Days 28, 42, 56, Weeks 24 and 32
Change from Baseline in expanded disability status scale (EDSS)
Time frame: Baseline, Weeks 8, 20, and 32
Change form Baseline in Multiple Sclerosis Functional Composite Scale (MFSC)
Time frame: Baseline, Weeks 8, 20, and 32
Change from Baseline in Symbol Digit Modalities Test (SDMT)
Time frame: Baseline, Weeks 8, 20, and 32
Change from Baseline in visual analog scale (VAS)
Time frame: Baseline, Weeks 8, 20, and 32
Change from Baseline in visual function test
Time frame: Baseline, Weeks 8, 20, and 32
Number of new or newly enlarging T2 hyperintense lesions
Time frame: Baseline and Week 32
Number of new gadolinium-enhanced lesions
Time frame: Baseline and Week 32
Number of new T1 hypointense lesions
Time frame: Baseline and Week 32
Whole brain atrophy
Time frame: Baseline and Week 32
Percent change in magnetization transfer ratio (MTR)
Time frame: Baseline and Week 32
Diffusion tensor imaging (DTI)
Time frame: Baseline and Week 32
Injection site pain assessment
Time frame: Pre-dose, 5 and 15 minutes and 24 hours post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2014.
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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
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing natalizumab in people with Relapsing-Remitting Multiple Sclerosis and Secondary Progressive Multiple Sclerosis, run by Biogen at 12 sites 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 3 inclusion and 3 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 9 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 12 sites 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum observed concentration (Cmax) of natalizumab (time frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56). The study lists 8 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 9 Sep 2014.