Natalizumab as an Efficacy Switch in Participants With Relapsing Multiple Sclerosis (MS) After Failure on Other Therapies

Relapsing Multiple Sclerosis Clinical Trial

— ESCALATE  

Official title:

A Phase 4 Multicenter, Open-Label, Single Arm Study to Evaluate Switching From BRACET/Gilenya® to Natalizumab in Subjects With Relapsing Forms of Multiple Sclerosis (MS)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02241785
• Other study ID #: 101MS409
• Secondary ID: 2013-005586-39
• Status: Terminated
• Phase: Phase 4
• First received: September 12, 2014
• Last updated: October 19, 2016
• Start date: September 2014
• Est. completion date: May 2016

Study information

• Verified date: October 2016
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to determine the efficacy of natalizumab (Tysabri, BG00002) in participants with relapsing forms of multiple sclerosis (MS) who have failed Gilenya or BRACET (Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera) as measured by the proportion of participants with no evidence of disease activity (NEDA) at Year 1. The secondary objectives in this study population are: Change in total T1 hypointense and total T2 hyperintense lesion volume; Proportion of participants with NEDA at Year 2; Evaluation of the impact of natalizumab on annualized relapse rate (ARR); and Change in Multiple Sclerosis Impact Scale-29 (MSIS-29) physical impact score.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 48
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Key Inclusion Criteria:

• Subjects of childbearing potential must practice effective contraception from Day -1 and be willing and able to continue contraception for duration of the study.

• Must have documented diagnosis of relapsing MS (McDonald 2010 Criteria [Polman 2011]) at Screening.

• Must have been treated with Gilenya or BRACET for at least the 6 months prior to Screening with no interruption of treatment. Prior treatment with natalizumab is allowed; however, there must be a minimum 1 year since last natalizumab infusion and the Screening visit of this study, and if discontinuation of natalizumab in the past was not due to intolerance, anti-natalizumab antibodies, or efficacy loss.

• Must have had disease activity in the 12 months prior to Screening while on Gilenya or BRACET (as defined by at least 1 Gd+ lesion OR at least 2 new T2 lesions (compared with an MRI done within 12 months of screening) OR clinical relapse, or EDSS progression of 1 point)

• Must have an EDSS score from 0 to 5.5 inclusive at Screening.

• Must have lymphocyte count that is documented as at or above the lower limit of normal (LLN) by the day before the first Tysabri infusion. If lymphocytes have not returned to LLN or above the day before the first Tysabri infusion (day 0), the subject has screen failed. The subject who screen fails is eligible to undergo Rescreening once; if additional Rescreening is considered, please contact the study medical monitor.

Key Exclusion Criteria:

• History or positive test result at Screening for human immunodeficiency virus (HIV).

• History or positive test result at Screening for hepatitis C virus antibody (HCV Ab) or current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis core antibody [HBcAb]).

• Prior treatment with natalizumab (either commercially or through a clinical study) within 1 year of Day -1.

• Contraindications to treatment with natalizumab as described in the Prescribing Information for each of the participating countries.

• Known allergy to natalizumab or any of its ingredients, or known to be anti-natalizumab antibody positive.

• Diagnosis of primary progressive MS, secondary progressive MS, and/or progressive-relapsing MS.

• An MS relapse that has occurred within the 30 days prior to Day -1 and/or the subject has not stabilized from a previous relapse prior to Day -1.

• Known active malignancies (subjects with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible).

• History of severe opportunistic infections (including PML) or any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal, or other major disease, as determined by the Investigator

• Clinically severe active infection within 1 month prior to Screening.

• Females breastfeeding, pregnant, or planning to become pregnant; women who are not post-menopausal or surgically sterile who are unwilling to practice contraception; women who have a positive pregnancy test result at Day -1.

• Prior history of immunosuppressant use (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab) in the last 12 months prior to Screening. Prior history of alemtuzumab use at any point in the past.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• natalizumab
Administered as specified in the treatment arm

Locations

Country	Name	City	State
United States	Research Site	Akron	Ohio
United States	Research Site	Aurora	Colorado
United States	Research Site	Cleveland	Ohio
United States	Research Site	Des Moines	Iowa
United States	Research Site	Fullerton	California
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Plainview	New York
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Round Rock	Texas
United States	Research Site	St. Louis	Missouri
United States	Research Site	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of participants who have NEDA as measured by the number of participants that do not experience Expanded Disability Status Scale (EDSS) progression for a sustained period of 12 weeks.	The EDSS is a method of quantifying disability in MS. The EDSS quantifies disability in 8 functional systems and allows neurologists to assign a Functional System Score (FSS) in each of these. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. Each of the FSS is an ordinal clinical rating scale ranging from 0 to 5 or 6. The final EDSS score is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.	At 1 year	No
Primary	The proportion of participants who have NEDA as measured by the number of participants that do not experience a relapse		At 1 year	No
Primary	The proportion of participants who have NEDA as measured by the number of participants that do not experience gadolinium enhancing (Gd+) positive lesions		At 1 year	No
Primary	The proportion of participants who have NEDA as measured by the number of participants that do not experience new T2 hyperintense lesions.		At 1 year	No
Primary	The proportion of participants who have NEDA as measured by the number of participants that do not experience new or enlarging T2 hyperintense lesions.		At 1 year	No
Secondary	Change in total T1 hypointense and total T2 hyperintense lesion volume		Baseline (Day -1) to week 56	No
Secondary	Change in total T1 hypointense and total T2 hyperintense lesion volume from Reset baseline (week 8) to week 56		Reset baseline (Week 8) to week 56	No
Secondary	The proportion of participants who have NEDA as measured by the number of participants that do not experience EDSS progression for a sustained period of 12 weeks.	From week 8 to week 104 with no 12-week confirmed EDSS progression determined at Week 116	Up to week 116	No
Secondary	The proportion of participants who have NEDA as measured by the number of participants that do not experience a relapse	Accompanied by no progression in EDSS at Week 116	Reset Baseline (Week 8) to Week 104	Yes
Secondary	The proportion of participants who have NEDA as measured by the number of participants that do not experience Gd+ positive lesions	Accompanied by no progression in EDSS at Week 116	Reset Baseline (Week 8) to Week 104	No
Secondary	The proportion of participants who have NEDA as measured by the number of participants that do not experience new T2 hyperintense lesions.	Accompanied by no progression in EDSS at Week 116	Reset Baseline (Week 8) to Week 104	No
Secondary	The proportion of participants who have NEDA as measured by the number of participants that do not experience newly enlarging T2 hyperintense lesions.	Accompanied by no progression in EDSS at Week 116	Reset Baseline (Week 8) to Week 104	No
Secondary	Annualized Relapse Rate		From Week 8 to Week 56 (Year 1), From Week 56 to Week 104 (Year 2) and across the 2 years (Week 8 to Week 104)	No
Secondary	Change in MSIS-29 physical impact	The MSIS-29 is a brief self-administered MS-specific instrument measuring physical (20 items) and mental/psychological (9 items) impact of MS. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health.	From baseline (Day -1) to week 56 and week104	No