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

NCT02241785 | Terminated Phase 4 Results

• 2 other identifiers: 101MS4092013-005586-39
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Relapsing Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With No Evidence of Disease Activity (NEDA) From Reset Baseline (Week 8) to Week 56

  The proportion of participants with NEDA, defined as follows: no Expanded Disability Status Scale (EDSS) progression (12-week sustained); no relapses; no gadolinium enhancing (Gd+) lesions; no new or enlarging T2 hyperintense lesions over 48 weeks after resetting the Baseline at Week 8 to remove contribution of combined unique active (CUA) lesions that occurred prior to Week 8, when natalizumab was not yet active. The EDSS quantifies disability in 8 functional systems. 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.

  Reset Baseline (Week 8) to Week 56

Secondary Outcomes (4)

• Change in T1 Unenhancing Lesion Volume and T2 Lesion Volume From Baseline (Day -1) to Reset Baseline (Week 8)

  Baseline (Day -1) to Reset Baseline (Week 8)

• Proportion of Participants With NEDA From Week 8 (Reset Baseline) to Week 104

  from Week 8 (Reset Baseline) to Week 104

• Pre- and Post-Natalizumab Infusion Annualized Relapse Rate (ARR) Comparison at Month 12

  From 12 months prior to natalizumab infusion and 12 months post-natalizumab infusion

• Change in MSIS-29 Physical Impact Scores From Baseline (Day -1) to Reset Baseline (Week 8)

  Baseline (Day -1) to Reset Baseline (Week 8)

Study Arms (1)

natalizumab

EXPERIMENTAL

natalizumab 300 mg intravenously (IV) every 4 weeks

Drug: natalizumab

Interventions

natalizumab DRUG

Administered as specified in the treatment arm

Also known as: BG00002, Tysabri

natalizumab

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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 Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera (BRACET) for at least the 12 months prior to Screening with no interruption of treatment greater than 1 month. 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 6 months prior to Screening while on Gilenya or BRACET (as defined by at least 1 gadolinium enhancing lesion OR at least 2 new T2 lesions compared with magnetic resonance imaging done within 12 months of screening OR clinical relapse, or Expanded Disability Status Scale \[EDSS\] 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.

You may not qualify if:

• History or positive test result at Screening for human immunodeficiency virus.
• History or positive test result at Screening for hepatitis C virus antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen and/or hepatitis core antibody).
• 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 progressive multifocal leukoencephalopathy) 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (11)

Research Site

Fullerton, California, 92835, United States

Location

Research Site

Aurora, Colorado, 80045, United States

Location

Research Site

Des Moines, Iowa, 50314, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Plainview, New York, 11803, United States

Location

Research Site

Raleigh, North Carolina, 27607-6010, United States

Location

Research Site

Akron, Ohio, 44320, United States

Location

Research Site

Cleveland, Ohio, 44195, United States

Location

Research Site

Knoxville, Tennessee, 37922, United States

Location

Research Site

Round Rock, Texas, 78681, United States

Location

Research Site

Tacoma, Washington, 98405, United States

Location

MeSH Terms

Interventions

Natalizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

As a result of early study termination and limited available data, no meaningful conclusions can be drawn.

Results Point of Contact

• Title: Biogen Study Medical Director
• Organization: Biogen

clinicaltrials@biogen.com

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2014
• First Posted: September 16, 2014
• Study Start: September 30, 2014
• Primary Completion: May 2, 2016
• Study Completion: May 2, 2016
• Last Updated: June 5, 2017
• Results First Posted: June 5, 2017

Record last verified: 2017-04

Locations

US (11)