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Safety and Efficacy Extension Study of Daclizumab High Yield Process (DAC HYP) in Participants With Multiple Sclerosis Who Have Completed Study 205MS201 (NCT00390221) to Treat Relapsing-Remitting Multiple Sclerosis (SELECTION)

Primary Purpose

Relapsing-Remitting Multiple Sclerosis

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

BIIB019 (Daclizumab High Yield Process)

Placebo

About this trial

This is an interventional treatment trial for Relapsing-Remitting Multiple Sclerosis focused on measuring MS, Multiple Sclerosis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

Participated in Study 205MS201 (NCT00390221) for at least 52 weeks and was compliant with the 205MS201 protocol in the opinion of the Investigator.

Key Exclusion Criteria:

Subjects with any significant change in their medical status from 205MS201 that would preclude administration of DAC HYP, as determined by the Investigator
Any subject who has permanently discontinued study treatment in Study 205MS201 except subjects who were unblinded during evaluation of an adverse event (AE) and found to be on placebo
Planned ongoing treatment with any approved or experimental treatment for MS except for the protocol-allowed use of concomitant interferon-beta

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Group 1: DAC HYP 150 mg

Group 1: DAC HYP 300 mg

Group 2: Washout then DAC HYP 150 mg

Group 2: DAC HYP 150 mg

Group 3: Washout then DAC HYP 300 mg

Group 3: DAC HYP 300 mg

Arm Description

Participants who received placebo in 205MS201 receive DAC HYP 150 mg subcutaneous (SC) injection every 4 weeks for a total of 13 doses.

Participants who received placebo in 205MS201 receive DAC HYP 300 mg SC injection every 4 weeks for a total of 13 doses.

Participants who received DAC HYP 150 mg SC injection in 205MS201 undergo a washout period (placebo SC every 4 weeks for a total of 5 doses) and then receive DAC HYP 150 mg SC every 4 weeks for a total of 8 doses.

Participants who received DAC HYP 150 mg SC injection in 205MS201 receive DAC HYP 150 mg SC every 4 weeks for a total of 13 doses.

Participants who received DAC HYP 300 mg SC in 205MS201 undergo a washout period (placebo SC every 4 weeks for a total of 5 doses) and then receive DAC HYP 300 mg SC every 4 weeks for a total of 8 doses.

Participants who received DAC HYP 300 mg SC in 205MS201 receive DAC HYP 300 mg SC every 4 weeks for a total of 13 doses.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-emergent Adverse Events (AEs)

Treatment-emergent AE: any untoward medical occurrence after the first dose of study treatment that did not necessarily have a causal relationship with this treatment. Serious AE (SAE): any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the subject at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect. An SAE could also have been a medically significant event that, in the opinion of the Investigator, jeopardized the subject or required intervention to prevent one of the other outcomes listed in the definition above.

Number of Participants With Abnormalities in Vital Signs

For participants who took DAC HYP during 205MS201 (NCT00390221) the baseline is defined as the baseline from 205MS201, and for participants who took placebo during 205MS201 the baseline is defined as the baseline from 205MS202 (NCT00870740). All post-baseline data are taken after first dose in 205MS202 only. SBP=systolic blood pressure; DBP=diastolic blood pressure; bpm=beats per minute; ↑ BL=increase from baseline; ↓ BL=decrease from baseline.

Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities

Hematology parameters evaluated include: white blood cells, lymphocytes, neutrophils, red blood cells (RBC), hemoglobin, and platelets.

Number of Participants With Abnormalities in Blood Chemistry Laboratory Data

For each abnormality a subject can be counted once. If a subject has more than one occurrence of the same abnormality the highest toxicity grade is counted. ALT=alanine aminotransferase; AST=aspartate aminotransferase; ALP=alkaline phosphatase; GGT=gamma-glutamyl transferase; TSH=thyroid stimulating hormone, ULN=upper limit of normal.

Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline

Number of participants positive and negative for ADAb and NAb, based on all post-baseline immunogenicity assessments during treatment period and follow-up. Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan.

Secondary Outcome Measures

Adjusted Annualized Relapse Rate

Relapses are 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 Independent Neurology Evaluation Committee (INEC). Relapse rate is calculated as: (Total number of relapses that occurred during the 205MS202 [NCT00870740] treatment phase divided by the total number of days followed in the treatment phase for 205MS202), multiplied by 365 days. Participants who received an alternative multiple sclerosis (MS) medication during 205MS201 (NCT00390221; Year 1) are not included in the summary of relapses and relapse rate for this study (Year 2). Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan.

Estimated Proportion of Participants With a Relapse

Relapses are defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the INEC. Estimated using Kaplan-Meier analysis where time to first relapse is calculated from date of first dose in the study to date of first confirmed relapse. Participants who received an alternative MS medication before the first relapse were censored at the time of taking the alternative MS medication.

Mean Number of New Gadolinium-enhancing Lesions

Evaluated by magnetic resonance imaging (MRI) by a central reader. Number of new Gd lesions since the previous scan (the previous scan for Week 20 was Week 52 of study 205MS201 [NCT00390221]). The number of Gd lesions may be imputed using last observation carried forward or using the mean value across all subjects within the treatment group. Baseline visits are not imputed. Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan.

Mean Number of New or Newly-enlarging T2 Hyperintense Lesions

Lesions detected on T2-weighted sequences represent a range of histopathology related to MS, including edema, inflammation, demyelination, gliosis, and axon loss. Evaluated by MRI by a central reader. New or newly enlarging T2 lesions since baseline of study 205MS202 (NCT00870740). For post-baseline visits, the number of T2 lesions may be imputed using the mean value across all participants within the treatment group, if the participant has non-missing baseline data. Baseline visits are not imputed. Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan.

Mean Volume of New T1 Hypointense Lesions

T1-weighted scans detect areas of hypointensity that represent a greater degree of tissue destruction and axon loss than T2 hyperintense lesions and are more highly correlated with clinical disability measures and neurological deficit. Evaluated by MRI by a central reader. Baseline is volume of new T1 hypointense lesions since baseline in study 205MS201 (NCT00390221). Scans at Week 20 and Week 52 in 205MS202 are relative to baseline in 205MS202 (NCT00870740). For post-baseline visits, the total volume of T1 lesions may be imputed using the mean value across all subjects within the treatment group. Baseline visits are not imputed.

Mean Percentage Change From Baseline in Total Lesion Volume of T2 Hyperintense Lesions

Lesions detected on T2-weighted sequences represent a range of histopathology related to MS, including edema, inflammation, demyelination, gliosis, and axon loss. Evaluated by MRI by a central reader. Baseline values = baseline for study 205MS202 (NCT00870740). For post-baseline visits, the total volume of T2 lesions may be imputed using the mean value across all subjects within the treatment group. Baseline visits are not imputed.

Mean Percentage Change From Baseline in Total Volume of Non-gadolinium (Gd)-Enhancing T1 Hypointense Lesions

T1-weighted scans detect areas of hypointensity that represent a greater degree of tissue destruction and axon loss than T2 hyperintense lesions and are more highly correlated with clinical disability measures and neurological deficit. Evaluated by MRI by a central reader. Baseline values = baseline for study 205MS202 (NCT00870740). For post-baseline visits, the total volume of T1 lesions may be imputed using the mean value across all participants within the treatment group. Baseline visits are not imputed.

Rate of Percentage Change From Baseline in Mean Total Brain Volume

Total brain volume was measured by MRI and analyzed by a central reader. Rate of percentage change from baseline calculated using an analysis of covariance adjusting for baseline normalized brain volume. Baseline values = baseline for study 205MS202 (NCT00870740). Missing values post-baseline were imputed using the average value across subjects in the treatment group.

Full Information

NCT ID

NCT00870740

First Posted

March 26, 2009

Last Updated

July 19, 2016

Sponsor

Biogen

Collaborators

AbbVie

1. Study Identification

Unique Protocol Identification Number

NCT00870740

Brief Title

Safety and Efficacy Extension Study of Daclizumab High Yield Process (DAC HYP) in Participants With Multiple Sclerosis Who Have Completed Study 205MS201 (NCT00390221) to Treat Relapsing-Remitting Multiple Sclerosis

Acronym

SELECTION

Official Title

A Double-Blind, Multicenter, Extension Study to Evaluate the Safety and Efficacy of DAC HYP in Subjects With Multiple Sclerosis Who Have Completed Treatment in Study 205MS201 (SELECT)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Completed

Study Start Date

February 2009 (undefined)

Primary Completion Date

May 2012 (Actual)

Study Completion Date

October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Biogen

Collaborators

AbbVie

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary objective of the study was to assess the safety and immunogenicity of extended treatment with DAC HYP. This evaluation included the following major components: An assessment of safety and immunogenicity of extended treatment with DAC HYP when administered to MS subjects who had completed 52 weeks of active therapy with DAC HYP in Study 201. An assessment of safety and immunogenicity during a 6-month washout period from DAC HYP. An assessment of safety and immunogenicity during reinitiation of therapy with DAC HYP after a 6-month washout period. An assessment of safety and immunogenicity of DAC HYP when administered to MS subjects who previously received placebo during Study 201. The secondary objective is to assess the durability of the effect of DAC HYP on multiple sclerosis (MS) disease activity as measured by brain magnetic resonance imaging (MRI) scans and clinical MS relapses.

Detailed Description

This study, an extension to Study 205MS201 (NCT00390221), will evaluate the long-term safety, efficacy, and immunogenicity of DAC HYP in MS. In Study 205MS201, study treatment was scheduled to stop at the Week 52 visit. This extension study will provide for the initiation of active therapy with DAC HYP among participants who received placebo during Weeks 0 through 52 in 205MS201. In addition, participants who received active therapy with DAC HYP during Weeks 0 through 52 in Study 205MS201 will continue DAC HYP therapy or resume DAC HYP therapy after a 6-month washout period in this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapsing-Remitting Multiple Sclerosis

Keywords

MS, Multiple Sclerosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

517 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1: DAC HYP 150 mg

Arm Type

Experimental

Arm Description

Participants who received placebo in 205MS201 receive DAC HYP 150 mg subcutaneous (SC) injection every 4 weeks for a total of 13 doses.

Arm Title

Group 1: DAC HYP 300 mg

Arm Type

Experimental

Arm Description

Participants who received placebo in 205MS201 receive DAC HYP 300 mg SC injection every 4 weeks for a total of 13 doses.

Arm Title

Group 2: Washout then DAC HYP 150 mg

Arm Type

Experimental

Arm Description

Arm Title

Group 2: DAC HYP 150 mg

Arm Type

Experimental

Arm Description

Participants who received DAC HYP 150 mg SC injection in 205MS201 receive DAC HYP 150 mg SC every 4 weeks for a total of 13 doses.

Arm Title

Group 3: Washout then DAC HYP 300 mg

Arm Type

Experimental

Arm Description

Arm Title

Group 3: DAC HYP 300 mg

Arm Type

Experimental

Arm Description

Participants who received DAC HYP 300 mg SC in 205MS201 receive DAC HYP 300 mg SC every 4 weeks for a total of 13 doses.

Intervention Type

Biological

Intervention Name(s)

BIIB019 (Daclizumab High Yield Process)

Other Intervention Name(s)

Daclizumab HYP, DAC HYP

Intervention Description

SC injection

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo SC injection

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-emergent Adverse Events (AEs)

Description

Time Frame

Up to 72 weeks

Title

Number of Participants With Abnormalities in Vital Signs

Description

Time Frame

Up to Week 72

Title

Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities

Description

Hematology parameters evaluated include: white blood cells, lymphocytes, neutrophils, red blood cells (RBC), hemoglobin, and platelets.

Time Frame

Up to 72 Weeks

Title

Number of Participants With Abnormalities in Blood Chemistry Laboratory Data

Description

Time Frame

Up to 72 Weeks

Title

Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline

Description

Time Frame

Up to 72 weeks

Secondary Outcome Measure Information:

Title

Adjusted Annualized Relapse Rate

Description

Time Frame

Up to 72 weeks

Title

Estimated Proportion of Participants With a Relapse

Description

Time Frame

Up to 72 weeks

Title

Mean Number of New Gadolinium-enhancing Lesions

Description

Time Frame

Week 20, Week 52

Title

Mean Number of New or Newly-enlarging T2 Hyperintense Lesions

Description

Time Frame

Baseline, Week 20, Week 52

Title

Mean Volume of New T1 Hypointense Lesions

Description

Time Frame

Baseline, Week 20, Week 52

Title

Mean Percentage Change From Baseline in Total Lesion Volume of T2 Hyperintense Lesions

Description

Lesions detected on T2-weighted sequences represent a range of histopathology related to MS, including edema, inflammation, demyelination, gliosis, and axon loss. Evaluated by MRI by a central reader. Baseline values = baseline for study 205MS202 (NCT00870740). For post-baseline visits, the total volume of T2 lesions may be imputed using the mean value across all subjects within the treatment group. Baseline visits are not imputed.

Time Frame

Baseline, Week 52

Title

Mean Percentage Change From Baseline in Total Volume of Non-gadolinium (Gd)-Enhancing T1 Hypointense Lesions

Description

T1-weighted scans detect areas of hypointensity that represent a greater degree of tissue destruction and axon loss than T2 hyperintense lesions and are more highly correlated with clinical disability measures and neurological deficit. Evaluated by MRI by a central reader. Baseline values = baseline for study 205MS202 (NCT00870740). For post-baseline visits, the total volume of T1 lesions may be imputed using the mean value across all participants within the treatment group. Baseline visits are not imputed.

Time Frame

Baseline, Week 52

Title

Rate of Percentage Change From Baseline in Mean Total Brain Volume

Description

Time Frame

Baseline, Week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Participated in Study 205MS201 (NCT00390221) for at least 52 weeks and was compliant with the 205MS201 protocol in the opinion of the Investigator. Key Exclusion Criteria: Subjects with any significant change in their medical status from 205MS201 that would preclude administration of DAC HYP, as determined by the Investigator Any subject who has permanently discontinued study treatment in Study 205MS201 except subjects who were unblinded during evaluation of an adverse event (AE) and found to be on placebo Planned ongoing treatment with any approved or experimental treatment for MS except for the protocol-allowed use of concomitant interferon-beta NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Biogen

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Brno

Country

Czech Republic

Facility Name

Research Site

City

Hraddec Kralove

Country

Czech Republic

Facility Name

Research Site

City

Olomouc

Country

Czech Republic

Facility Name

Research Site

City

Plzen

Country

Czech Republic

Facility Name

Research Site

City

Prague

Country

Czech Republic

Facility Name

Research Site

City

Teplice

Country

Czech Republic

Facility Name

Research Site

City

Bayreuth

Country

Germany

Facility Name

Research Site

City

Erlangen

Country

Germany

Facility Name

Research Site

City

Marburg

Country

Germany

Facility Name

Research Site

City

Osnabruck

Country

Germany

Facility Name

Research Site

City

Regensburg

Country

Germany

Facility Name

Research Site

City

Rostock

Country

Germany

Facility Name

Research Site

City

Budapest

Country

Hungary

Facility Name

Research Site

City

Debrecen

Country

Hungary

Facility Name

Research Site

City

Esztergom

Country

Hungary

Facility Name

Research Site

City

Gyor

Country

Hungary

Facility Name

Research Site

City

Kecskemet

Country

Hungary

Facility Name

Research Site

City

Miskolc

Country

Hungary

Facility Name

Research Site

City

Nyiregyhaza

Country

Hungary

Facility Name

Research Site

City

Siofok

Country

Hungary

Facility Name

Research Site

City

Zalaegerszeg

Country

Hungary

Facility Name

Research Site

City

Andra-Pradeash

Country

India

Facility Name

Research Site

City

Bangalore

Country

India

Facility Name

Research Site

City

Jaipur

Country

India

Facility Name

Research Site

City

Kolkata

Country

India

Facility Name

Research Site

City

Mumbai

Country

India

Facility Name

Research Site

City

Visakhapatnam

Country

India

Facility Name

Research Site

City

Bialystok

Country

Poland

Facility Name

Research Site

City

Gdansk

Country

Poland

Facility Name

Research Site

City

Katowice

Country

Poland

Facility Name

Research Site

City

Krakow

Country

Poland

Facility Name

Research Site

City

Lodz

Country

Poland

Facility Name

Research Site

City

Lublin

Country

Poland

Facility Name

Research Site

City

Warsaw

Country

Poland

Facility Name

Research Site

City

Warszawa

Country

Poland

Facility Name

Research Site

City

Kazan

Country

Russian Federation

Facility Name

Research Site

City

Krasnoyarsk

Country

Russian Federation

Facility Name

Research Site

City

Moscow

Country

Russian Federation

Facility Name

Research Site

City

Nizhny Novgorod

Country

Russian Federation

Facility Name

Research Site

City

Novosibirsk

Country

Russian Federation

Facility Name

Research Site

City

Omsk

Country

Russian Federation

Facility Name

Research Site

City

Samara

Country

Russian Federation

Facility Name

Research Site

City

Smolensk

Country

Russian Federation

Facility Name

Research Site

City

St Petersburg

Country

Russian Federation

Facility Name

Research Site

City

Ufa

Country

Russian Federation

Facility Name

Research Site

City

Yaroskavl

Country

Russian Federation

Facility Name

Research Site

City

Chernivtsi

Country

Ukraine

Facility Name

Research Site

City

Dnipropetrovsk

Country

Ukraine

Facility Name

Research Site

City

Donetsk

Country

Ukraine

Facility Name

Research Site

City

Kharkiv

Country

Ukraine

Facility Name

Research Site

City

Kiev

Country

Ukraine

Facility Name

Research Site

City

Lviv

Country

Ukraine

Facility Name

Research Site

City

Poltava

Country

Ukraine

Facility Name

Research Site

City

Zaporizhzhya

Country

Ukraine

Facility Name

Research Site

City

Zaporozhye

Country

Ukraine

Facility Name

Research Site

City

Devon

Country

United Kingdom

Facility Name

Research Site

City

London

Country

United Kingdom

Facility Name

Research Site

City

Nottingham

Country

United Kingdom

Facility Name

Research Site

City

Sheffield

Country

United Kingdom

Facility Name

Research Site

City

Stoke-on-Trent

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

27411694

Citation

Gold R, Stefoski D, Selmaj K, Havrdova E, Hurst C, Holman J, Tornesi B, Akella S, McCroskery P. Pregnancy Experience: Nonclinical Studies and Pregnancy Outcomes in the Daclizumab Clinical Study Program. Neurol Ther. 2016 Dec;5(2):169-182. doi: 10.1007/s40120-016-0048-2. Epub 2016 Jul 13.

Results Reference

derived

PubMed Identifier

24656609

Citation

Giovannoni G, Gold R, Selmaj K, Havrdova E, Montalban X, Radue EW, Stefoski D, McNeill M, Amaravadi L, Sweetser M, Elkins J, O'Neill G; SELECTION Study Investigators. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial. Lancet Neurol. 2014 May;13(5):472-81. doi: 10.1016/S1474-4422(14)70039-0. Epub 2014 Mar 19.

Results Reference

derived

Links:

URL

http://www.nationalmssociety.org

Description

The website of the National Multiple Sclerosis Society, an organization dedicated to providing information to individuals with MS, their families and healthcare providers.

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Safety and Efficacy Extension Study of Daclizumab High Yield Process (DAC HYP) in Participants With Multiple Sclerosis Who Have Completed Study 205MS201 (NCT00390221) to Treat Relapsing-Remitting Multiple Sclerosis (SELECTION)

Relapsing-Remitting Multiple Sclerosis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial