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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03689972
Ethics application status
Date submitted
27/09/2018
Date registered
1/10/2018
Date last updated
22/07/2019

Titles & IDs
Public title
A Study to Evaluate Efficacy, Safety, and Tolerability of 6-Week Extended Interval Dosing of Natalizumab (BG00002) in Participants With Relapsing-Remitting Multiple Sclerosis (RRMS) Switching From Treatment With 4-Week Natalizumab Standard Interval Dosing (SID) in Relation to Continued SID Treatment
Scientific title
A Randomized, Controlled, Open-Label, Rater-Blinded, Phase 3b Study of the Efficacy, Safety, and Tolerability of 6-Week Extended Interval Dosing 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
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

Experimental: Standard Interval Dosing (SID) - Participants will receive natalizumab 300 milligram (mg) intravenous (IV) infusion every 4 weeks (-2/+5 days) up to Week 72.

Experimental: Extended Interval Dosing (EID) - Participants will receive natalizumab 300 mg IV infusion every 6 weeks (-2/+5 days) up to Week 72.


Treatment: Drugs: Natalizumab
Natalizumab 300 mg IV infusion

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

Outcomes
Primary outcome [1] 0 0
Number of New or Newly Enlarging T2 Hyperintense Lesions at Week 72 - Number of new or newly enlarging T2 hyperintense lesions will be analysed by magnetic resonance imaging (MRI) scans of brain. New MRI scans will be compared with the prior MRI scans to analyse the number of new or newly enlarging T2 hyperintense lesions.
Timepoint [1] 0 0
Week 72
Secondary outcome [1] 0 0
Time to First Relapse as Adjudicated by an Independent Neurology Evaluation Committee (INEC) - A multiple sclerosis (MS) relapse will be defined as the onset of new or recurrent neurological symptoms, not associated with fever, infection, severe stress, or drug toxicity, lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination. Only relapses confirmed by an INEC will be included in the analysis.
Timepoint [1] 0 0
Up to Week 72
Secondary outcome [2] 0 0
Number of new Gadolinium (Gd) Enhancing and new T1 Hypointense Lesions at Weeks 24, 48 and 72 - Number of new Gd enhancing and new T1 hypointense lesions on brain will be analysed by MRI scans of brain. New MRI scans will be compared with the prior MRI scans to analyse number of new Gd enhancing and new T1 hypointense lesions.
Timepoint [2] 0 0
Weeks 24, 48 and 72
Secondary outcome [3] 0 0
Annualized Relapse Rate at Week 72 - An MS relapse will be defined as the onset of new or recurrent neurological symptoms, not associated with fever, infection, severe stress, or drug toxicity, lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination. Only relapses confirmed by an INEC will be included in the analysis.
Timepoint [3] 0 0
Week 72
Secondary outcome [4] 0 0
Number of New or Newly Enlarging T2 Hyperintense Lesions at Weeks 24 and 48 - Number of new or newly enlarging T2 hyperintense lesions will be analysed by MRI scans of brain. New MRI scans will be compared with the prior MRI scans to analyse the number of new or newly enlarging T2 hyperintense lesions.
Timepoint [4] 0 0
Weeks 24 and 48
Secondary outcome [5] 0 0
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) - An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore 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. A SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event.
Timepoint [5] 0 0
Up to Week 96
Secondary outcome [6] 0 0
Time to Expanded Disability Status Scale (EDSS) Worsening as Confirmed After at Least 24 Weeks - Confirmed EDSS worsening is defined as an increase of at least 1.0 point from a baseline EDSS score = 1.0 or an increase of at least 1.5 points from a baseline EDSS score of 0 that is confirmed after at least 24 weeks.
Timepoint [6] 0 0
Week 24, 48, 72 and 84

Eligibility
Key inclusion criteria
Key

- 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) <=5.5 at screening.

- No relapses in the last 12 months prior to randomization, as determined by the
enrolling Investigator.

Key
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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. 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
Recruiting
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,VIC
Recruitment hospital [1] 0 0
Research Site - St Leonards
Recruitment hospital [2] 0 0
Research Site - Sydney
Recruitment hospital [3] 0 0
Research Site - Box Hill
Recruitment hospital [4] 0 0
Research Site - Melbourne
Recruitment hospital [5] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment outside Australia
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Ramat Gan
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Catania
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to evaluate the efficacy of natalizumab extended
interval dosing (EID) in subjects who have previously been treated with natalizumab standard
interval dosing (SID) for at least 12 months, in relation to continued SID treatment.

The secondary objectives are to evaluate additional clinical and MRI based efficacy
endpoints, disability worsening and safety of EID in subjects who have previously been
treated with natalizumab SID for at least 12 months, in relation to continued SID treatment.
Trial website
https://clinicaltrials.gov/show/NCT03689972
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
US Biogen Clinical Trial Center
Address 0 0
Country 0 0
Phone 0 0
866-633-4636
Fax 0 0
Email 0 0
clinicaltrials@biogen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03689972