Relapsing-Remitting Multiple Sclerosis (RRMS)
Conditions
Keywords
Multiple Sclerosis, Daclizumab, Tysabri-Switch
Brief summary
The primary objective of the study is to evaluate the effects of treatment with daclizumab on the proportion of participants relapse-free at 6 months in Relapsing-Remitting Multiple Sclerosis (RRMS) participants, who switched from treatment with natalizumab to daclizumab due to safety concerns. The secondary objectives of this study in this study population are to evaluate the effects of daclizumab on the following: 1) Multiple Sclerosis (MS) relapse activity including the annualized relapse rate (ARR) and the proportion of participants experiencing relapses requiring hospitalization and/or steroid treatment; 2) MS-related outcomes measured using magnetic resonance imaging (MRI); 3) Safety and tolerability in participants previously treated with natalizumab.
Interventions
DRUGDaclizumab
High yield formulation
Sponsors
AbbVie
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Must have documented diagnosis of RRMS (McDonald 2010 Criteria) at screening \[Polman 2011\]. * Must have been treated with natalizumab for at least the 12 months prior to screening and have not missed 2 or more consecutive scheduled doses. * Must be naïve to daclizumab and other forms of daclizumab such as Zenapax® prior to enrollment. * Must have a confirmed Expanded Disability Status Scale (EDSS) score of 0 to 5.5, inclusive, at screening. * Female participants of childbearing potential must practice effective contraception from Day -1 and be willing and able to continue contraception for duration of the study. Key
Exclusion criteria
* Current participation in another investigational study. * Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS (as defined by Lublin and Reingold) \[Lublin 2014\]. * Females breastfeeding, pregnant, or planning to become pregnant; or women who have a positive pregnancy test result during screening. * History of drug or alcohol abuse (as defined by the Investigator) within 1 year prior to screening. * History of severe hypersensitivity (e.g., anaphylaxis or anaphylactoid reactions) to the active ingredient or any of the excipients. * History of severe opportunistic infections (including progressive multifocal leukoencephalopathy (PML)) or any clinically significant, cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal, or other major disease, as determined by the Investigator. * Discontinued natalizumab due to suspicion of PML. * Known active malignancies (participants with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible). * The participant is using another MS therapy concomitantly. * Known history of human immunodeficiency virus (HIV). * Positive test result for Hepatitis C virus (test for hepatitis C virus antibody \[HCV Ab\]) or hepatitis B virus (test for hepatitis B surface antigen \[HBsAg\] and/or hepatitis B core antibody \[HBcAb\]). * The participant has been treated with immunosuppressive or immunomodulating treatments including mitoxantrone, azathioprine, methotrexate, cyclophosphamide, or mycophenolate mofetil. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Relapse-free at Month 6 | Month 6 | Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist. The Kaplan-Meier estimate of the percentage of participants relapse-free at Month 6 is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Relapse Requiring Hospitalization and/or Steroid Treatment at Month 12 | Month 12 | Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist. |
| Annualized Relapse Rate (ARR) at Month 12 | Month 12 | Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist. The ARR was calculated by tabulating the total number of relapses experienced in the group divided by the number of days up to the end of Month 12, and the ratio then multiplied by 365. |
| Number of Participants With New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions at Months 6 and 12 | Months 6 and 12 | New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions were assessed using magnetic resonance imaging (MRI). |
| Percentage of Participants Relapse-free at Month 12 | Month 12 | Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist. |
| Permanent Discontinuation Rate of Daclizumab at Month 12 | Month 12 | Permanent Discontinuation Rate was calculated as the ratio of number of participants who had permanently discontinued daclizumab prior to Month 12 over the total number of participants who received at least 1 dose of daclizumab in the study. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | First dose of study drug to within 30 days of last dose (up to 11 months) | An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death or in the view of the Investigator, places the participant at immediate risk of death or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability or results in a birth defect. |
| Number of Participants With Clinically Relevant Shifts in Laboratory Assessments | First dose of study drug to within 30 days of last dose (up to 11 months) | Clinical Laboratory assessments were tests of Chemistry and Hematology. The investigator determined if any of the laboratory results were clinically relevant shifts from Baseline. |
| Number of Participants With New and Newly Enlarged T2 Hypointense Lesions at Months 6 and 12 | Months 6 and 12 | New and newly enlarged T2 Hypointense Lesions were measured by MRI. |
Countries
Canada, Germany, Italy, Puerto Rico, United States
Participant flow
Recruitment details
Participants enrolled in the study at 11 investigative sites in Canada, Germany, Italy, and the United States from 05 April 2017 to 12 September 2018.
Pre-assignment details
Participants who discontinued treatment with natalizumab due to safety concerns were enrolled to receive daclizumab 150 milligrams (mg) per 1.0 milliliter (mL).
Participants by arm
| Arm | Count |
|---|---|
| Daclizumab Participants previously treated with natalizumab for at least 12 months and who discontinued treatment, received daclizumab 150 mg per 1.0 mL administered subcutaneously once a month for up to 11 months. | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Consent withdrawn | 1 |
| Overall Study | Investigator decision | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Reason not Specified | 3 |
| Overall Study | Study terminated by sponsor | 9 |
Baseline characteristics
| Characteristic | Daclizumab |
|---|---|
| Age, Continuous | 36.9 years STANDARD_DEVIATION 9.71 |
| Race/Ethnicity, Customized Black or African American | 4 Participants |
| Race/Ethnicity, Customized Not Reported Due to Confidentiality Regulation | 27 Participants |
| Race/Ethnicity, Customized Other (Aboriginal) | 1 Participants |
| Race/Ethnicity, Customized White | 9 Participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 41 |
| other Total, other adverse events | 23 / 41 |
| serious Total, serious adverse events | 9 / 41 |
Outcome results
Primary
Percentage of Participants Relapse-free at Month 6
Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist. The Kaplan-Meier estimate of the percentage of participants relapse-free at Month 6 is reported.
Time frame: Month 6
Population: FAS included all participants enrolled in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclizumab | Percentage of Participants Relapse-free at Month 6 | 66.615 percentage of participants |
Secondary
Annualized Relapse Rate (ARR) at Month 12
Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist. The ARR was calculated by tabulating the total number of relapses experienced in the group divided by the number of days up to the end of Month 12, and the ratio then multiplied by 365.
Time frame: Month 12
Population: The study was terminated. No participants reached the 12-month time point.
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death or in the view of the Investigator, places the participant at immediate risk of death or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability or results in a birth defect.
Time frame: First dose of study drug to within 30 days of last dose (up to 11 months)
Population: Safety Population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Daclizumab | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 9 Participants |
| Daclizumab | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 27 Participants |
Secondary
Number of Participants With Clinically Relevant Shifts in Laboratory Assessments
Clinical Laboratory assessments were tests of Chemistry and Hematology. The investigator determined if any of the laboratory results were clinically relevant shifts from Baseline.
Time frame: First dose of study drug to within 30 days of last dose (up to 11 months)
Population: Safety Population included all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daclizumab | Number of Participants With Clinically Relevant Shifts in Laboratory Assessments | 0 Participants |
Secondary
Number of Participants With New and Newly Enlarged T2 Hypointense Lesions at Months 6 and 12
New and newly enlarged T2 Hypointense Lesions were measured by MRI.
Time frame: Months 6 and 12
Population: FAS included all participants enrolled in the study. Number Analyzed is the number of participants with available assessment. No participants reached the 12-month time point since the study was terminated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Daclizumab | Number of Participants With New and Newly Enlarged T2 Hypointense Lesions at Months 6 and 12 | Month 6 | 3 Participants |
Secondary
Number of Participants With New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions at Months 6 and 12
New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions were assessed using magnetic resonance imaging (MRI).
Time frame: Months 6 and 12
Population: FAS included all participants enrolled in the study. Number Analyzed is the number of participants with available assessment. No data was collected for T1 Hypointense Lesions at Month 6. No participants reached the 12-month time point since the study was terminated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Daclizumab | Number of Participants With New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions at Months 6 and 12 | Month 6, Gd+ Lesions | 3 Participants |
Secondary
Percentage of Participants Experiencing Relapse Requiring Hospitalization and/or Steroid Treatment at Month 12
Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist.
Time frame: Month 12
Population: The study was terminated. No participants reached the 12-month time point.
Secondary
Percentage of Participants Relapse-free at Month 12
Relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist.
Time frame: Month 12
Population: The study was terminated. No participants reached the 12-month time point.
Secondary
Permanent Discontinuation Rate of Daclizumab at Month 12
Permanent Discontinuation Rate was calculated as the ratio of number of participants who had permanently discontinued daclizumab prior to Month 12 over the total number of participants who received at least 1 dose of daclizumab in the study.
Time frame: Month 12
Population: The study was terminated. No participants reached the 12-month time point.