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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03689972




Registration number
NCT03689972
Ethics application status
Date submitted
27/09/2018
Date registered
1/10/2018

Titles & IDs
Public title
A Study to Evaluate Efficacy, Safety, and Tolerability of EID of Natalizumab (BG00002) in Participants With RRMS Switching From Treatment With Natalizumab SID in Relation to Continued SID Treatment- Followed by Extension Study Comprising SC and IV Natalizumab Administration
Scientific title
A Randomized, Controlled, Open-Label, Rater-Blinded, Phase 3b Study of the Efficacy, Safety, and Tolerability of 6-Week Extended Interval Dosing (EID) of Natalizumab (BG00002) in Subjects With Relapsing-Remitting Multiple Sclerosis Switching From Treatment With 4-Week Natalizumab Standard Interval Dosing (SID) in Relation to Continued SID Treatment - Followed by an Open-Label Crossover Extension Study Comprising Subcutaneous and Intravenous Natalizumab Administration
Secondary ID [1] 0 0
2018-002145-11
Secondary ID [2] 0 0
101MS329
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis, Relapsing-Remitting 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Natalizumab
Treatment: Drugs - Natalizumab

Experimental: Part 1: IV Q4W - Participants received natalizumab 300 mg intravenous (IV) infusion once Q4W up to Week 72.

Experimental: Part 1: IV Q6W - Participants received natalizumab 300 mg IV infusion once Q6W up to Week 72.

Experimental: Part 2: Run-in Period: IV Q6W - Participants who completed Part 1 or were newly enrolled in Part 2 received natalizumab 300 mg IV infusion Q6W from Week 72 through Week 102.

Experimental: Part 2: Crossover Period: IV Q6W, then SC Q6W - Participants who completed run-in period of Part 2 were randomized to receive natalizumab 300 mg IV infusion Q6W from Week 108 through Week 126 followed by natalizumab 300 mg subcutaneous (SC) injection Q6W from Week 132 through Week 150 along with a single dose of natalizumab 300 mg SC injection or IV infusion as per participant's choice at Week 156.

Experimental: Part 2: Crossover Period: SC Q6W, then IV Q6W - Participants who completed run-in period of Part 2 were randomized to receive natalizumab 300 mg SC injection Q6W from Week 108 through Week 126 followed by natalizumab 300 mg IV infusion Q6W from Week 132 through Week 150 along with a single dose of natalizumab 300 mg SC injection or IV infusion as per participant's choice at Week 156.


Treatment: Drugs: Natalizumab
Natalizumab 300 mg IV infusion.

Treatment: Drugs: Natalizumab
Natalizumab 300 mg SC injection or IV infusion.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Week 72
Timepoint [1] 0 0
Week 72
Primary outcome [2] 0 0
Part 2: Percentage of Participants Indicating a Preference for Natalizumab SC Administration at the End of Crossover Period of Part 2
Timepoint [2] 0 0
Week 150
Secondary outcome [1] 0 0
Part 1: Time to First Relapse as Adjudicated by an Independent Neurology Evaluation Committee (INEC)
Timepoint [1] 0 0
Up to Week 72
Secondary outcome [2] 0 0
Part 1: Annualized Relapse Rate at Week 72
Timepoint [2] 0 0
Week 72
Secondary outcome [3] 0 0
Part 1: Time to Expanded Disability Status Scale (EDSS) Worsening
Timepoint [3] 0 0
Up to Week 72
Secondary outcome [4] 0 0
Part 1: Mean Number of New T1 Hypointense Lesions at Weeks 24, 48, and 72
Timepoint [4] 0 0
Weeks 24, 48, and 72
Secondary outcome [5] 0 0
Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Weeks 24 and 48
Timepoint [5] 0 0
Weeks 24 and 48
Secondary outcome [6] 0 0
Part 1: Mean Number of New Gadolinium (Gd) Enhancing Lesions at Weeks 24, 48, and 72
Timepoint [6] 0 0
Weeks 24, 48, and 72
Secondary outcome [7] 0 0
Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [7] 0 0
Baseline up to Week 84
Secondary outcome [8] 0 0
Part 2: Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores During the Crossover Period
Timepoint [8] 0 0
Part 2 Baseline (Week 108) up to Week 156
Secondary outcome [9] 0 0
Part 2: Mean Time for Drug Preparation and Drug Administration During the Crossover Period
Timepoint [9] 0 0
Week 108 up to Week 156
Secondary outcome [10] 0 0
Part 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Timepoint [10] 0 0
Part 2: Baseline (Week 108) up to Week 180
Secondary outcome [11] 0 0
Part 2: Percentage of Participants With Anti-Natalizumab Antibodies During the Crossover Period
Timepoint [11] 0 0
Part 2 Baseline (Week 108) up to Week 156
Secondary outcome [12] 0 0
Part 2: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions During the Crossover Period
Timepoint [12] 0 0
Part 2 Baseline (Week 108) up to Week 156
Secondary outcome [13] 0 0
Part 2: Time to First Relapse During the Crossover Period
Timepoint [13] 0 0
Part 2 Baseline (Week 108) up to Week 156
Secondary outcome [14] 0 0
Part 2: Annualized Relapse Rate During the Crossover Period
Timepoint [14] 0 0
Part 2 Baseline (Week 108) up to Week 156
Secondary outcome [15] 0 0
Part 2: Change From Baseline in EDSS Score During the Crossover Period
Timepoint [15] 0 0
Part 2 Baseline (Week 108) up to Week 156
Secondary outcome [16] 0 0
Part 2: Mean Number of New Gd Enhancing Lesions During the Crossover Period
Timepoint [16] 0 0
Week 108 up to Week 156
Secondary outcome [17] 0 0
Part 2: Mean Number of New T1 Hypointense Lesions During the Crossover Period
Timepoint [17] 0 0
Week 108 up to Week 156
Secondary outcome [18] 0 0
Part 2: Mean Percentage Change From Baseline in Brain Volume During the Crossover Period
Timepoint [18] 0 0
Part 2 Baseline (Week 108) up to Week 156
Secondary outcome [19] 0 0
Part 2: Change From Baseline in Cortical and Thalamic Brain Region Volume During the Crossover Period
Timepoint [19] 0 0
Part 2 Baseline (Week 108) up to Week 156
Secondary outcome [20] 0 0
Part 2: Trough Serum Concentration of Natalizumab (Ctrough) During the Crossover Period
Timepoint [20] 0 0
Pre-dose at Weeks 108, 114, 120, 126, 132, 138, 144, 150, and 156
Secondary outcome [21] 0 0
Part 2: Mean Trough a4 Integrin Saturation During the Crossover Period
Timepoint [21] 0 0
Pre-dose at Weeks 108, 114, 120, 126, 132, 138, 144, 150, and 156

Eligibility
Key inclusion criteria
Key

For Part 1:

* Ability of the participant to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
* Diagnosis of relapsing remitting multiple sclerosis (RRMS) according to the McDonald criteria [Thompson 2018].
* Treatment with natalizumab as disease-modifying monotherapy for RRMS that is consistent with the approved dosing for a minimum of 12 months prior to randomization. The participant must have received at least 11 doses of natalizumab in the 12 months prior to randomization with no missed doses in the 3 months prior to randomization.
* Expanded Disability Status Scale (EDSS) score <=5.5 at screening.
* No relapses in the last 12 months prior to randomization, as determined by the enrolling Investigator.

For Part 2:

* Ability of the participants to understand the purpose and risks of the study and provide signed and dated informed consent for Part 2 and authorization to use confidential health information in accordance with national and local participant privacy regulations.
* Completed Part 1 Week 72 visit while remaining on their randomized treatment assignment of Q4W or Q6W.

Key
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
For Part 1:

* Primary and secondary progressive multiple sclerosis (MS).
* MRI positive for Gd-enhancing lesions at screening.
* Participants for whom MRI is contraindicated (e.g., have a contraindicated pacemaker or other contraindicated implanted metal device, have suffered, or are at risk for, side effects from Gd, or have claustrophobia that cannot be medically managed).
* History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic (including diabetes), urologic, pulmonary, neurologic (except for RRMS), dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical study, in the opinion of the Investigator.
* Presence of anti-natalizumab antibodies at screening.

For Part 2:

* Participants treated with natalizumab Q6W was reverted to natalizumab Q4W by choice or as rescue treatment in Part 1.
* Participant received treatment with any MS disease-modifying therapy other than natalizumab in Part 1 or in the period between Part 1 and Part 2.
* History of human immunodeficiency virus or history of other immunodeficient conditions.
* Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 30 days (or 5 half-lives of the agent, whichever is longer) prior to the Baseline Visit or at any time during this study.
* Inability to comply with study requirements.
* Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the participant unsuitable for enrollment.

The inclusion and exclusion criteria for new participants who did not participate in Part 1 of the study are the same as those for participants who did participate in Part 1.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 0 0
Brain and Mind Centre - Sydney
Recruitment hospital [3] 0 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [4] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [5] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [6] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment postcode(s) [3] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
Nevada
Country [15] 0 0
United States of America
State/province [15] 0 0
New Jersey
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
Oregon
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
Tennessee
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Utah
Country [24] 0 0
United States of America
State/province [24] 0 0
Virginia
Country [25] 0 0
United States of America
State/province [25] 0 0
Washington
Country [26] 0 0
United States of America
State/province [26] 0 0
Wisconsin
Country [27] 0 0
Belgium
State/province [27] 0 0
Bruxelles
Country [28] 0 0
Belgium
State/province [28] 0 0
Edegem
Country [29] 0 0
Belgium
State/province [29] 0 0
La Louvière
Country [30] 0 0
Canada
State/province [30] 0 0
Ontario
Country [31] 0 0
Canada
State/province [31] 0 0
Quebec
Country [32] 0 0
France
State/province [32] 0 0
Bordeaux
Country [33] 0 0
France
State/province [33] 0 0
Caen
Country [34] 0 0
France
State/province [34] 0 0
Lille
Country [35] 0 0
France
State/province [35] 0 0
Nice
Country [36] 0 0
France
State/province [36] 0 0
Saint Herblain
Country [37] 0 0
France
State/province [37] 0 0
Strasbourg
Country [38] 0 0
Germany
State/province [38] 0 0
Bamberg
Country [39] 0 0
Germany
State/province [39] 0 0
Berlin
Country [40] 0 0
Germany
State/province [40] 0 0
Bochum
Country [41] 0 0
Germany
State/province [41] 0 0
Erbach
Country [42] 0 0
Germany
State/province [42] 0 0
Essen
Country [43] 0 0
Germany
State/province [43] 0 0
Freiburg
Country [44] 0 0
Germany
State/province [44] 0 0
Marburg
Country [45] 0 0
Germany
State/province [45] 0 0
Muenster
Country [46] 0 0
Germany
State/province [46] 0 0
Munich
Country [47] 0 0
Germany
State/province [47] 0 0
Stuttgart
Country [48] 0 0
Israel
State/province [48] 0 0
Ramat Gan
Country [49] 0 0
Italy
State/province [49] 0 0
Catania
Country [50] 0 0
Italy
State/province [50] 0 0
Cefalù
Country [51] 0 0
Italy
State/province [51] 0 0
Milano
Country [52] 0 0
Italy
State/province [52] 0 0
Napoli
Country [53] 0 0
Italy
State/province [53] 0 0
Pozzilli
Country [54] 0 0
Netherlands
State/province [54] 0 0
Breda
Country [55] 0 0
Netherlands
State/province [55] 0 0
Nieuwegein
Country [56] 0 0
Netherlands
State/province [56] 0 0
Sittard
Country [57] 0 0
Spain
State/province [57] 0 0
Catalonia
Country [58] 0 0
Spain
State/province [58] 0 0
Murcia
Country [59] 0 0
Spain
State/province [59] 0 0
Madrid
Country [60] 0 0
Spain
State/province [60] 0 0
Malaga
Country [61] 0 0
Spain
State/province [61] 0 0
Sevilla
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Greater London
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Merseyside
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Strathclyde
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Tyne & Wear
Country [66] 0 0
United Kingdom
State/province [66] 0 0
London
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Nottingham
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Salford
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Sheffield
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Swansea

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Please refer data queries to [email protected].


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.