Multiple Sclerosis (MS)
Conditions
Keywords
Progressive multiple sclerosis, Elezanumab, ABT-555
Brief summary
The purpose of this study is to evaluate the safety and efficacy of elezanumab in participants with progressive Multiple Sclerosis (PMS).
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
* Diagnosis of primary-progressive multiple sclerosis (PPMS) or non-relapsing secondary-progressive multiple sclerosis (SPMS) and no relapses for at least 24 months. * Evidence of physical disability according to Expanded Disability Status Scale (EDSS) or Timed 25-Foot Walk (T25FW) or 9-Hole Peg Test.
Exclusion criteria
* Treatment with any of the following within the 6 months prior to Screening: natalizumab; cyclosporine; azathioprine; methotrexate; mycophenolate mofetil; intravenous immunoglobulin (IVIg); any interferon product; and intravenous (IV), oral, or intrathecal corticosteroids for the purposes of disease modification. * Treatment with the following within 1 year prior to Screening: cyclophosphamide or alemtuzumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Overall Response Score (ORS) | 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 Expanded Disability Status Scale (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). |
Countries
Canada, United States
Participant flow
Recruitment details
A total of 123 subjects from 35 sites in the United States & Canada were enrolled into the study, were randomized, and received at least 1 dose of study drug. Of these, 108 completed treatment
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants randomized to receive placebo by intravenous infusion.
placebo: solution for infusion | 43 |
| Elezanumab 400mg Dose Participants randomized to receive 400mg of elezanumab by intravenous infusion.
elezanumab: solution for infusion | 40 |
| Elezanumab 1800 mg Dose Participants randomized to receive 1800mg of elezanumab by intravenous infusion.
elezanumab: solution for infusion | 40 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | COVID -19 Logistical Restrictions | 0 | 0 | 1 |
| Overall Study | Sponsor Discontinued the Study | 4 | 3 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Elezanumab 1800 mg Dose | Elezanumab 400mg Dose |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 121 Participants | 39 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 118 Participants | 37 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 6 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 42 Participants | 111 Participants | 37 Participants | 32 Participants |
| Region of Enrollment Canada | 13 participants | 32 participants | 9 participants | 10 participants |
| Region of Enrollment United States | 30 participants | 91 participants | 31 participants | 30 participants |
| Sex: Female, Male Female | 24 Participants | 59 Participants | 21 Participants | 14 Participants |
| Sex: Female, Male Male | 19 Participants | 64 Participants | 19 Participants | 26 Participants |
| Type of MS Non-relapsing secondary progressive multiple sclerosis (nrSPMS) | 24 Participants | 64 Participants | 21 Participants | 19 Participants |
| Type of MS Primary progressive MS (PPMS) | 19 Participants | 59 Participants | 19 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 43 | 1 / 40 | 0 / 40 |
| other Total, other adverse events | 34 / 43 | 29 / 40 | 31 / 40 |
| serious Total, serious adverse events | 2 / 43 | 5 / 40 | 3 / 40 |
Outcome results
Primary
Mean 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-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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Overall Response Score (ORS) | -0.74 score on a scale | Standard Error 0.167 |
| Elezanumab 400mg Dose | Mean Overall Response Score (ORS) | -0.75 score on a scale | Standard Error 0.176 |
| Elezanumab 1800 mg Dose | Mean Overall Response Score (ORS) | -0.64 score on a scale | Standard Error 0.17 |
Secondary
Disability Improvement Response Rate
Disability improvement response rate is assessed based on the Expanded Disability Status Scale Plus (EDSS+). EDSS+ is comprised of Expanded Disability Status Scale (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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Disability Improvement Response Rate | 3 Participants |
| Elezanumab 400mg Dose | Disability Improvement Response Rate | 7 Participants |
| Elezanumab 1800 mg Dose | Disability Improvement Response Rate | 9 Participants |
Comparison: Analyzed using a logistic regression model with corresponding baseline value as a covariate and treatment as a main effect. 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: [0.485, 10.259]
Comparison: Analyzed using a logistic regression model with corresponding baseline value as a covariate and treatment as a main effect. 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: [0.899, 16.561]
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).
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Response Score (ORS) | -0.47 score on a scale | Standard Error 0.134 |
| Elezanumab 400mg Dose | Overall Response Score (ORS) | 0.00 score on a scale | Standard Error 0.136 |
| Elezanumab 1800 mg Dose | Overall Response Score (ORS) | -0.21 score on a scale | Standard Error 0.139 |
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Response Score (ORS) | -0.28 score on a scale | Standard Error 0.176 |
| Elezanumab 400mg Dose | Overall Response Score (ORS) | -0.27 score on a scale | Standard Error 0.194 |
| Elezanumab 1800 mg Dose | Overall Response Score (ORS) | -0.53 score on a scale | Standard Error 0.188 |
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Response Score (ORS) | -0.45 score on a scale | Standard Error 0.159 |
| Elezanumab 400mg Dose | Overall Response Score (ORS) | -0.48 score on a scale | Standard Error 0.178 |
| Elezanumab 1800 mg Dose | Overall Response Score (ORS) | -0.52 score on a scale | Standard Error 0.169 |