Trial Outcomes & Findings for Efficacy and Safety of Daclizumab in Participants With RRMS Switching From Natalizumab (NCT NCT02881567)

NCT ID: NCT02881567

Last Updated: 2019-09-27

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

41 participants

Primary outcome timeframe

Month 6

Results posted on

2019-09-27

Participant Flow

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.

Participants who discontinued treatment with natalizumab due to safety concerns were enrolled to receive daclizumab 150 milligrams (mg) per 1.0 milliliter (mL).

Participant milestones

Participant milestones
Measure
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.
Overall Study
STARTED
41
Overall Study
COMPLETED
23
Overall Study
NOT COMPLETED
18

Reasons for withdrawal

Reasons for withdrawal
Measure
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.
Overall Study
Adverse Event
1
Overall Study
Lost to Follow-up
3
Overall Study
Consent withdrawn
1
Overall Study
Investigator decision
1
Overall Study
Study terminated by sponsor
9
Overall Study
Reason not Specified
3

Baseline Characteristics

Efficacy and Safety of Daclizumab in Participants With RRMS Switching From Natalizumab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Daclizumab
n=41 Participants
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.
Age, Continuous
36.9 years
STANDARD_DEVIATION 9.71 • n=5 Participants
Sex: Female, Male
Female
28 Participants
n=5 Participants
Sex: Female, Male
Male
13 Participants
n=5 Participants
Race/Ethnicity, Customized
White
9 Participants
n=5 Participants
Race/Ethnicity, Customized
Black or African American
4 Participants
n=5 Participants
Race/Ethnicity, Customized
Not Reported Due to Confidentiality Regulation
27 Participants
n=5 Participants
Race/Ethnicity, Customized
Other (Aboriginal)
1 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Month 6

Population: FAS included all participants enrolled in the study.

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.

Outcome measures

Outcome measures
Measure
Daclizumab
n=41 Participants
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.
Percentage of Participants Relapse-free at Month 6
66.615 percentage of participants

SECONDARY outcome

Timeframe: Month 12

Population: The study was terminated. No participants reached the 12-month time point.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 12

Population: The study was terminated. No participants reached the 12-month time point.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 12

Population: The study was terminated. No participants reached the 12-month time point.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions were assessed using magnetic resonance imaging (MRI).

Outcome measures

Outcome measures
Measure
Daclizumab
n=41 Participants
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.
Number of Participants With New Gadolinium-Enhanced (Gd+) and T1 Hypointense Lesions at Months 6 and 12
Month 6, Gd+ Lesions
3 Participants

SECONDARY outcome

Timeframe: 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.

New and newly enlarged T2 Hypointense Lesions were measured by MRI.

Outcome measures

Outcome measures
Measure
Daclizumab
n=41 Participants
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.
Number of Participants With New and Newly Enlarged T2 Hypointense Lesions at Months 6 and 12
Month 6
3 Participants

SECONDARY outcome

Timeframe: Month 12

Population: The study was terminated. No participants reached the 12-month time point.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Daclizumab
n=41 Participants
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.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with AEs
27 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with SAEs
9 Participants

SECONDARY outcome

Timeframe: 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.

Clinical Laboratory assessments were tests of Chemistry and Hematology. The investigator determined if any of the laboratory results were clinically relevant shifts from Baseline.

Outcome measures

Outcome measures
Measure
Daclizumab
n=41 Participants
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.
Number of Participants With Clinically Relevant Shifts in Laboratory Assessments
0 Participants

Adverse Events

Daclizumab

Serious events: 9 serious events
Other events: 23 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Daclizumab
n=41 participants at risk
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.
Blood and lymphatic system disorders
Lymphadenopathy
2.4%
1/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Gastrointestinal disorders
Gastrointestinal ulcer
2.4%
1/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Hepatobiliary disorders
Cholelithiasis
2.4%
1/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Infections and infestations
Encephalitis
2.4%
1/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Infections and infestations
Influenza
2.4%
1/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Infections and infestations
Oesophageal candidiasis
2.4%
1/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Infections and infestations
Subcutaneous abscess
2.4%
1/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
2.4%
1/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Nervous system disorders
Multiple sclerosis relapse
4.9%
2/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Skin and subcutaneous tissue disorders
Drug reaction with eosinophilia and systemic symptoms
2.4%
1/41 • First dose of study drug to within 30 days of last dose (up to 11 months)

Other adverse events

Other adverse events
Measure
Daclizumab
n=41 participants at risk
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.
Blood and lymphatic system disorders
Lymphadenopathy
7.3%
3/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Gastrointestinal disorders
Nausea
12.2%
5/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Gastrointestinal disorders
Vomiting
7.3%
3/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
General disorders
Injection site pain
17.1%
7/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Infections and infestations
Influenza
22.0%
9/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Infections and infestations
Nasopharyngitis
9.8%
4/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Nervous system disorders
Migraine
7.3%
3/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Nervous system disorders
Multiple sclerosis relapse
17.1%
7/41 • First dose of study drug to within 30 days of last dose (up to 11 months)
Psychiatric disorders
Depression
9.8%
4/41 • First dose of study drug to within 30 days of last dose (up to 11 months)

Additional Information

Biogen Study Medical Director

Biogen

Phone: 866-633-4636

Results disclosure agreements

  • Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
  • Publication restrictions are in place

Restriction type: OTHER