Multiple Sclerosis (MS)
Conditions
Keywords
Relapsing multiple sclerosis, Multiple sclerosis, Elezanumab, ABT-555
Brief summary
The purpose of this study is to evaluate the safety and efficacy of elezanumab in participants with relapsing Multiple Sclerosis (RMS).
Interventions
DRUGelezanumab
solution for infusion
DRUGplacebo
solution for infusion
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participant has diagnosis of relapsing remitting multiple sclerosis (RRMS) or secondary-progressive multiple sclerosis (SPMS) with relapses within the past 24 months. * Participant has cranial magnetic resonance imaging (MRI) demonstrating lesion(s) consistent with multiple sclerosis (MS). * Participant has evidence of physical disability according to Expanded Disability Status Scale (EDSS) or Timed 25-Foot Walk (T25FW) or 9-Hole Peg Test.
Exclusion criteria
\- Participants must not have experienced or be recovering from a clinical MS relapse within 6 months of Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Overall Response Score (ORS) at Week 52 | Week 52 | The ORS is a composite score derived from 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the non-dominant hand (9HPT-ND). Clinically significant worsening = -1, no change = 0, clinically significant improvement = +1. The ORS is the sum of these scores for the EDSS: Timed 25-Foot Walk, 9-Hole Peg Test-dominant, and 9-Hole Peg Test-nondominant and ranges from -4 to + 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disability Improvement Response Rate | Week 52 | Disability improvement response rate is assessed based on the Expanded Disability Status Scale Plus (EDSS+). EDSS+ is comprised of EDSS, Timed 25-Foot Walk (T25FW) and 9-Hole Peg Tests (9HPT). |
| Overall Response Score (ORS) | Week 12 | The ORS is a composite score derived from 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the non-dominant hand (9HPT-ND). Clinically significant worsening = -1, no change = 0, clinically significant improvement = +1. The ORS is the sum of these scores for the EDSS, Timed 25-Foot Walk, 9-Hole Peg Test-dominant and 9-Hole Peg Test-non-dominant and ranges from -4 to + 4. |
Countries
Canada, United States
Participant flow
Recruitment details
A total of 208 subjects from 44 sites in the United States & Canada were enrolled into the study and were randomized: 208 subjects received at least 1 dose of study drug. Of the 208 subjects who received study drug, 182 completed treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants randomized to receive double-blind placebo by intravenous infusion.
placebo: solution for infusion | 70 |
| Elezanumab Dose 1 Participants randomized to receive double-blind elezanumab Dose 1 by intravenous infusion.
elezanumab: solution for infusion | 69 |
| Elezanumab Dose 2 Participants randomized to receive double-blind elezanumab Dose 2 by intravenous infusion.
elezanumab: solution for infusion | 69 |
| Total | 208 |
Baseline characteristics
| Characteristic | Placebo | Elezanumab Dose 1 | Elezanumab Dose 2 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 70 Participants | 69 Participants | 69 Participants | 208 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 4 Participants | 6 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 65 Participants | 63 Participants | 188 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Non-White | 10 Participants | 7 Participants | 6 Participants | 23 Participants |
| Race/Ethnicity, Customized White | 60 Participants | 62 Participants | 62 Participants | 184 Participants |
| Region of Enrollment Canada | 1 participants | 5 participants | 4 participants | 10 participants |
| Region of Enrollment United States | 69 participants | 64 participants | 65 participants | 198 participants |
| Sex: Female, Male Female | 46 Participants | 45 Participants | 47 Participants | 138 Participants |
| Sex: Female, Male Male | 24 Participants | 24 Participants | 22 Participants | 70 Participants |
| Type of Multiple Sclerosis (MS) relapsing remitting MS (RRMS) | 66 Participants | 67 Participants | 66 Participants | 199 Participants |
| Type of Multiple Sclerosis (MS) relapsing secondary-progressive MS (rSPMS) | 4 Participants | 2 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 70 | 0 / 69 | 0 / 69 |
| other Total, other adverse events | 52 / 70 | 48 / 69 | 54 / 69 |
| serious Total, serious adverse events | 6 / 70 | 7 / 69 | 4 / 69 |
Outcome results
Primary
Mean Overall Response Score (ORS) at Week 52
The ORS is a composite score derived from 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the non-dominant hand (9HPT-ND). Clinically significant worsening = -1, no change = 0, clinically significant improvement = +1. The ORS is the sum of these scores for the EDSS: Timed 25-Foot Walk, 9-Hole Peg Test-dominant, and 9-Hole Peg Test-nondominant and ranges from -4 to + 4.
Time frame: Week 52
Population: The Modified Intent-to-Treat (mITT) Analysis Set consists of all randomized subjects who received at least 1 dose of study drug. Subjects were grouped according to treatment as randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Overall Response Score (ORS) at Week 52 | 0.04 score on a scale | Standard Error 0.175 |
| Elezanumab Dose 1 | Mean Overall Response Score (ORS) at Week 52 | -0.17 score on a scale | Standard Error 0.179 |
| Elezanumab Dose 2 | Mean Overall Response Score (ORS) at Week 52 | -0.17 score on a scale | Standard Error 0.177 |
Secondary
Disability Improvement Response Rate
Disability improvement response rate is assessed based on the Expanded Disability Status Scale Plus (EDSS+). EDSS+ is comprised of EDSS, Timed 25-Foot Walk (T25FW) and 9-Hole Peg Tests (9HPT).
Time frame: Week 52
Population: The Modified Intent-to-Treat (mITT) Analysis Set consists of all randomized subjects who received at least 1 dose of study drug. Subjects were grouped according to treatment as randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Disability Improvement Response Rate | 18 Participants |
| Elezanumab Dose 1 | Disability Improvement Response Rate | 20 Participants |
| Elezanumab Dose 2 | Disability Improvement Response Rate | 13 Participants |
Comparison: Logistic regression model for EDSS+ includes baseline values for EDSS, Timed 25-Foot Walk, 9-Hole Peg Test-dominant, 9-Hole Peg Test-nondominant, and treatment as a main effect. Subjects with missing values were imputed as non-responders.95% CI: [0.559, 2.584]
Comparison: Logistic regression model for EDSS+ includes baseline values for EDSS, Timed 25-Foot Walk, 9-Hole Peg Test-dominant, 9-Hole Peg Test-nondominant, and treatment as a main effect. Subjects with missing values were imputed as non-responders.95% CI: [0.266, 1.421]
Secondary
Overall Response Score (ORS)
The ORS is a composite score derived from 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the non-dominant hand (9HPT-ND). Clinically significant worsening = -1, no change = 0, clinically significant improvement = +1. The ORS is the sum of these scores for the EDSS, Timed 25-Foot Walk, 9-Hole Peg Test-dominant and 9-Hole Peg Test-non-dominant and ranges from -4 to + 4.
Time frame: Week 12
Population: The Modified Intent-to-Treat (mITT) Analysis Set consists of all randomized subjects who received at least 1 dose of study drug. Subjects were grouped according to treatment as randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Response Score (ORS) | 0.05 score on a scale | Standard Error 0.153 |
| Elezanumab Dose 1 | Overall Response Score (ORS) | -0.06 score on a scale | Standard Error 0.159 |
| Elezanumab Dose 2 | Overall Response Score (ORS) | 0.12 score on a scale | Standard Error 0.15 |
Secondary
Overall Response Score (ORS)
The ORS is a composite score derived from 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the non-dominant hand (9HPT-ND). Clinically significant worsening = -1, no change = 0, clinically significant improvement = +1. The ORS is the sum of these scores for the EDSS, Timed 25-Foot Walk, 9-Hole Peg Test-dominant and 9-Hole Peg Test-non-dominant and ranges from -4 to + 4.
Time frame: Week 24
Population: The Modified Intent-to-Treat (mITT) Analysis Set consists of all randomized subjects who received at least 1 dose of study drug. Subjects were grouped according to treatment as randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Response Score (ORS) | -0.04 score on a scale | Standard Error 0.167 |
| Elezanumab Dose 1 | Overall Response Score (ORS) | -0.13 score on a scale | Standard Error 0.175 |
| Elezanumab Dose 2 | Overall Response Score (ORS) | -0.06 score on a scale | Standard Error 0.168 |
Secondary
Overall Response Score (ORS)
The ORS is a composite score derived from 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the non-dominant hand (9HPT-ND). Clinically significant worsening = -1, no change = 0, clinically significant improvement = +1. The ORS is the sum of these scores for the EDSS, Timed 25-Foot Walk, 9-Hole Peg Test-dominant and 9-Hole Peg Test-non-dominant and ranges from -4 to + 4.
Time frame: Week 36
Population: The Modified Intent-to-Treat (mITT) Analysis Set consists of all randomized subjects who received at least 1 dose of study drug. Subjects were grouped according to treatment as randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Response Score (ORS) | 0.09 score on a scale | Standard Deviation 0.18 |
| Elezanumab Dose 1 | Overall Response Score (ORS) | -0.10 score on a scale | Standard Deviation 0.184 |
| Elezanumab Dose 2 | Overall Response Score (ORS) | -0.17 score on a scale | Standard Deviation 0.183 |