Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis
Brief summary
The purpose of the study is to evaluate the effectiveness and safety of CNTO 1275 in patients with Multiple Sclerosis
Detailed description
Multiple sclerosis (MS) is a life-long disease that usually starts in young adults. In MS, inflammation and damage to nerve cells occur in the brain and spinal cord. Symptoms of MS are quite variable and may range from being mild to severe and from short to long lasting. People with MS may have a wide variety of symptoms ranging from mild to disabling. Some of thesymptoms of MS include visual disturbances such as double vision, weakness in arms or legs,difficulty with coordination, fatigue, changes in sensations such as numbness and tingling, or difficulties with concentration or memory.The drug being tested in this research study is an antibody called CNTO 1275. Antibodies are natural substances made by the body that stick to and react with other substances in the body that may cause diseases. The body makes antibodies mainly to fight infections. CNTO 1275 is an antibody that has been manufactured in the laboratory. In the test tube, CNTO 1275 sticks to and blocks the activity of a naturally occurring substance in the body called interleukin 12 (IL-12).Higher than normal levels of IL-12 have been found in people who have MS. CNTO 1275 has been tested in animals with a condition similar to MS. In those animals, IL-12 was over-produced.Animals treated with CNTO 1275 showed decreased symptoms of the condition.The purpose of this study is to better understand the safety and effectiveness of CNTO 1275 in people who have relapsing-remitting MS Patients will receive subcutaneous injections of 30, 100, 200 mg of CNTO 1275 or placebo at Weeks 0, 1, 2, 3, 7, 11, 15, and 19 or 100 mgs at weeks 0,1,2,3,11 and 19 and placebo at wks 7 and 15.
Interventions
DRUGCNTO 1275
Sponsors
Centocor BV
Centocor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have a definite diagnosis of Relapsing remitting Multiple Sclerosis * Have a history of at least 1 of the following:a. A minimum of 2 relapses of MS within the previous 2 years but not within the 1-month period prior to screening. b. A relapse of MS within the previous 6 months but not within the 1-monthperiod prior to screening
Exclusion criteria
* Have a CNS disease (eg, CNS lymphoma, systemic lupus erythematous) * Have significant bulbar involvement of MS or other neurologic deficits * Have a decubitus ulcer * Have received immunomodulatory therapies within 3 months of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Cumulative Number of Newly Gadolinium-enhancing T1-weighted Lesions on Cranial Magnetic Resonance Imaging (MRI)s Through Week 23. | Week 23 | A newly Gadolinium (Gd) enhancing T1-weighted lesion is defined as a lesion that is enhanced on a current cranial MRI scan but was not classified as a newly Gd enhancing T1-weighted lesion on the previous MRI scan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapses of Multiple Sclerosis (MS) Through Week 23 | Week 23 | Clinical relapse of MS is defined as any acute neurological event, reported by the patient, that is characterized by new or worsening signs or symptoms of MS lasting at least 48 hours after a stable period of at least 30 days that is considered, in the judgment of the study physician (treating neurologist), to be a clinical relapse of MS. |
| Change From Baseline in Expanded Disability Status Scale (EDSS) | Baseline, Week 23 | The EDSS is based on an independent neurologist's examination of 8 functional systems and is used to classify multiple sclerosis (MS) severity, progression, disability, and evaluate treatment results. A numeric score ranging from 0 (normal) to 10 (death) is produced, the change from baseline of the EDSS score ranges from -9 to 10. |
Participant flow
Recruitment details
A total of 249 patients were enrolled in the trial to receive either placebo or ustekinumab (CNTO 1275). There were 38 investigative sites in North America, Europe and Australia.
Participants by arm
| Arm | Count |
|---|---|
| Group I: Placebo Patients received Placebo subcutaneous (SC) injection(s) at Weeks 0, 1, 2, 3, 7, 11, 15, and 19 | 49 |
| Group II: Ustekinumab 27 mg Every 4 Weeks Patients received 27 mg ustekinumab SC injection at Weeks 0, 1, 2, 3, 7, 11, 15, and 19. | 50 |
| Group III: Ustekinumab 90 mg Every 8 Weeks Patients received 90 mg ustekinumab SC injection at Weeks 0, 1, 2, 3, 11, and 19. Placebo SC injection at Weeks 7 and 15. | 50 |
| Group IV: Ustekinumab 90 mg Every 4 Weeks Patients received 90 mg ustekinumab SC injection at Weeks 0, 1, 2, 3, 7, 11, 15, and 19. | 50 |
| Group V: Ustekinumab 180 mg Every 4 Weeks Patients received 180 mg ustekinumab SC injections at Weeks 0, 1, 2, 3, 7, 11, 15, and 19. | 50 |
| Total | 249 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other | 38 | 41 | 41 | 37 | 33 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Group I: Placebo | Group II: Ustekinumab 27 mg Every 4 Weeks | Group III: Ustekinumab 90 mg Every 8 Weeks | Group IV: Ustekinumab 90 mg Every 4 Weeks | Group V: Ustekinumab 180 mg Every 4 Weeks | Total |
|---|---|---|---|---|---|---|
| Age Continuous | 36.3 Years STANDARD_DEVIATION 10.65 | 39.0 Years STANDARD_DEVIATION 10.34 | 38.6 Years STANDARD_DEVIATION 11.53 | 39.8 Years STANDARD_DEVIATION 11.01 | 41.1 Years STANDARD_DEVIATION 8.34 | 39.0 Years STANDARD_DEVIATION 10.46 |
| Sex: Female, Male Female | 37 Participants | 32 Participants | 37 Participants | 33 Participants | 36 Participants | 175 Participants |
| Sex: Female, Male Male | 12 Participants | 18 Participants | 13 Participants | 17 Participants | 14 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 49 | 35 / 51 | 34 / 47 | 38 / 52 | 44 / 50 |
| serious Total, serious adverse events | 1 / 49 | 3 / 51 | 0 / 47 | 2 / 52 | 1 / 50 |
Outcome results
Primary
The Cumulative Number of Newly Gadolinium-enhancing T1-weighted Lesions on Cranial Magnetic Resonance Imaging (MRI)s Through Week 23.
A newly Gadolinium (Gd) enhancing T1-weighted lesion is defined as a lesion that is enhanced on a current cranial MRI scan but was not classified as a newly Gd enhancing T1-weighted lesion on the previous MRI scan.
Time frame: Week 23
Population: Intent to treat. Missing data was imputed. The average number of newly Gd enhancing T1-weighted lesions from all valid visits for the patient will be used when prohibited medications are initiated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group I: Placebo | The Cumulative Number of Newly Gadolinium-enhancing T1-weighted Lesions on Cranial Magnetic Resonance Imaging (MRI)s Through Week 23. | 1.20 Lesions |
| Group II: Ustekinumab 27 mg Every 4 Weeks | The Cumulative Number of Newly Gadolinium-enhancing T1-weighted Lesions on Cranial Magnetic Resonance Imaging (MRI)s Through Week 23. | 1.00 Lesions |
| Group III: Ustekinumab 90 mg Every 8 Weeks | The Cumulative Number of Newly Gadolinium-enhancing T1-weighted Lesions on Cranial Magnetic Resonance Imaging (MRI)s Through Week 23. | 2.00 Lesions |
| Group IV: Ustekinumab 90 mg Every 4 Weeks | The Cumulative Number of Newly Gadolinium-enhancing T1-weighted Lesions on Cranial Magnetic Resonance Imaging (MRI)s Through Week 23. | 2.40 Lesions |
| Group V: Ustekinumab 180 mg Every 4 Weeks | The Cumulative Number of Newly Gadolinium-enhancing T1-weighted Lesions on Cranial Magnetic Resonance Imaging (MRI)s Through Week 23. | 2.00 Lesions |
Comparison: Hypothesis: The null hypothesis of no effect among the treatment groups was tested against the alternative hypothesis that the cumulative number of newly Gd-enhancing T1-weighted lesions on cranial MRIs through Week 23 would decrease monotonically with dose at a significance level of 0.05.p-value: 0Jonckheere Terpstra
Secondary
Change From Baseline in Expanded Disability Status Scale (EDSS)
The EDSS is based on an independent neurologist's examination of 8 functional systems and is used to classify multiple sclerosis (MS) severity, progression, disability, and evaluate treatment results. A numeric score ranging from 0 (normal) to 10 (death) is produced, the change from baseline of the EDSS score ranges from -9 to 10.
Time frame: Baseline, Week 23
Population: Intent to treat. Missing data was imputed. Missing EDSS scores was replaced with the last non-missing EDSS value observed (last observation carried forward).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group I: Placebo | Change From Baseline in Expanded Disability Status Scale (EDSS) | 0.00 Units on a scale |
| Group II: Ustekinumab 27 mg Every 4 Weeks | Change From Baseline in Expanded Disability Status Scale (EDSS) | 0.00 Units on a scale |
| Group III: Ustekinumab 90 mg Every 8 Weeks | Change From Baseline in Expanded Disability Status Scale (EDSS) | 0.00 Units on a scale |
| Group IV: Ustekinumab 90 mg Every 4 Weeks | Change From Baseline in Expanded Disability Status Scale (EDSS) | 0.00 Units on a scale |
| Group V: Ustekinumab 180 mg Every 4 Weeks | Change From Baseline in Expanded Disability Status Scale (EDSS) | 0.00 Units on a scale |
p-value: 0.72Wilcoxon (Mann-Whitney)
p-value: 0.152Wilcoxon (Mann-Whitney)
p-value: 0.431Wilcoxon (Mann-Whitney)
Comparison: Hypothesis: The null hypothesis is no difference between any ustekinumab treatment groups and placebo at a significant level of 0.05 for comparison for each treatment group with placebo..p-value: 0.292Wilcoxon (Mann-Whitney)
Secondary
Relapses of Multiple Sclerosis (MS) Through Week 23
Clinical relapse of MS is defined as any acute neurological event, reported by the patient, that is characterized by new or worsening signs or symptoms of MS lasting at least 48 hours after a stable period of at least 30 days that is considered, in the judgment of the study physician (treating neurologist), to be a clinical relapse of MS.
Time frame: Week 23
Population: Missing data remained missing. No treatment failure rule was implemented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group I: Placebo | Relapses of Multiple Sclerosis (MS) Through Week 23 | 0.00 Relapses |
| Group II: Ustekinumab 27 mg Every 4 Weeks | Relapses of Multiple Sclerosis (MS) Through Week 23 | 0.00 Relapses |
| Group III: Ustekinumab 90 mg Every 8 Weeks | Relapses of Multiple Sclerosis (MS) Through Week 23 | 0.00 Relapses |
| Group IV: Ustekinumab 90 mg Every 4 Weeks | Relapses of Multiple Sclerosis (MS) Through Week 23 | 0.00 Relapses |
| Group V: Ustekinumab 180 mg Every 4 Weeks | Relapses of Multiple Sclerosis (MS) Through Week 23 | 0.00 Relapses |
p-value: 0.8922-sided Wilcoxon Mann-Whitney
p-value: 0.5992-sided Wilcoxon Mann-Whitney
p-value: 0.5172-sided Wilcoxon Mann-Whitney
Comparison: Hypothesis: The null hypothesis is no difference between any ustekinumab treatment groups and placebo at a significant level of 0.05 for comparison for each treatment group.p-value: 0.9672-sided Wilcoxon Mann-Whitney