A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis (ASCEND in SPMS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT01416181
First received: July 21, 2011
Last updated: September 12, 2013
Last verified: July 2013
  Purpose

This is a Phase 3b, multicenter, international study conducted in 2 parts. Upon completion of the placebo-controlled period (Part 1), subjects will have the option of enrolling in a 2-year open-label extension (Part 2).

Part 1: The primary objective of the study is to investigate whether treatment with natalizumab slows the accumulation of disability not related to relapses in subjects with secondary progressive multiple sclerosis (SPMS).

The secondary objectives of Part 1 of this study are: To determine whether treatment with natalizumab improves the condition of subjects in this study population, including measurements such as walking speed and ability, magnetic resonance imaging (MRI), Expanded Disability Status Scale (EDSS) and subject-reported quality of life.

Part 2: The primary objective of Part 2 of the study is to evaluate the safety profile of natalizumab in subjects with SPMS.

The secondary objectives of Part 2 of the study are as follows: To investigate long-term disability (based on clinical or patient-reported assessments) in subjects with SPMS receiving natalizumab treatment for approximately 4 years; To assess change in brain volume and T2 lesion volume.


Condition Intervention Phase
Secondary Progressive Multiple Sclerosis
Drug: natalizumab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis, With Optional Open-Label Extension

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • Part 1: percentage of subjects experiencing confirmed progression of disability in one or more of the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), or 9-Hole Peg Test (9HPT) [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]
  • Part 2: The number of patients with Adverse Events and Serious Adverse Events [ Time Frame: 218 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Part 1: The proportion of subjects with consistent improvement in Timed 25-Foot Walk (T25FW) [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]
  • Part 1: The change from baseline in subject-reported ambulatory status as measured by the 12-Item MS Walking Scale (MSWS-12) [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]
  • Part 1: The change from baseline in manual ability score based on the ABILHAND Questionnaire [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]
  • Part 1: The change from baseline in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical) score [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]
  • Part 1: The change from Week 24 in whole brain volume using magnetic resonance imaging [ Time Frame: Up to week 96 ] [ Designated as safety issue: No ]
  • Part 1: The proportion of subjects experiencing confirmed worsening in individual Expanded Disability Status Scale (EDSS) Physical Functional System scores [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]
  • Part 2: The change from baselines (Part 1) in percentage of patients with disability worsening as measured by changes in Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), or Expanded Disability Status Scale (EDSS) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Absolute change from Baseline (Part 1) in Timed 25-Foot Walk (T25FW) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Percentage change from Baseline (Part 2) in Timed 25-Foot Walk (T25FW) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Absolute change from baselines (Part 1) in 9-Hole Peg Test (9HPT) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Percentage change from baseline (Part 1) in 9-Hole Peg Test (9HPT) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Absolute change from baseline (Part 1) in Expanded Disability Status Scale (EDSS) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Percentage change from baseline (Part 1) in Expanded Disability Status Scale (EDSS) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Absolute change from baseline (Part 1) in the 6-Minute Walk Test (6MWT) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Percentage change from baseline (Part 1) in the 6-Minute Walk Test (6MWT) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Absolute change from baseline (Part 1) in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Percentage change from baseline (Part 1) in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Absolute change from baseline (Part 1) in the Symbol Digit Modalities Test (SDMT) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Percentage change from baseline (Part 1) in the Symbol Digit Modalities Test (SDMT) [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Absolute change from baseline (Part 2) in the Work Productivity and Activity Impairment - Multiple Sclerosis (WPAI-MS) Questionnaire [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Percentage change from baseline (Part 2) in the Work Productivity and Activity Impairment - Multiple Sclerosis (WPAI-MS) Questionnaire [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Percentage change from baseline (Part 1) in whole brain volume [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Percentage change from baseline (Part 1) in gray matter brain volume [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Absolute change from Baseline (Part 1) in number of new/enlarging T2 lesions [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]
  • Part 2: Percentage change from baseline (Part 1) in number of new/enlarging T2 lesions [ Time Frame: Up to week 204 ] [ Designated as safety issue: No ]

Estimated Enrollment: 856
Study Start Date: July 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 Natalizumab; Part 2 Open-label Natalizumab
Part 1: participants were randomized to 300 mg of natalizumab intravenously every 4 weeks. Part 2: participants transitioned to open-label Natalizumab every 4 weeks.
Drug: natalizumab
300mg of natalizumab intravenously every 4 weeks
Other Name: Tysabri
Experimental: Part 1: Placebo; Part 2 Open-label Natalizumab
Part 1: participants were randomized to Placebo intravenously every 4 weeks. Part 2: participants transitioned to open-label Natalizumab every 4 weeks.
Drug: natalizumab
300mg of natalizumab intravenously every 4 weeks
Other Name: Tysabri
Drug: Placebo
placebo intravenously every 4 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 58 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Major Inclusion Criteria (Part 1):

  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
  • secondary progressive multiple sclerosis (SPMS) defined as relapsing-remitting disease followed by progression of disability independent of or not explained by multiple sclerosis (MS) relapses for at least 2 years.
  • Expanded Disability Status Scale (EDSS) score of 3.0 to 6.5, inclusive.
  • Multiple Sclerosis Severity Score (MSSS) of 4 or higher.
  • Documented confirmed evidence of disease progression independent of clinical relapses over the 1 year prior to enrollment as defined in the Study Reference Guide.

Major Exclusion Criteria (Part 1):

  • relapsing remitting multiple sclerosis (RRMS) or primary progressive multiple sclerosis (MS) as defined by the revised McDonald Committee criteria.
  • Clinical relapse (within 3 months) prior to randomization.
  • Timed 25-Foot Walk (T25FW) test of >30 seconds during the screening period.
  • Any value below the lower limit of normal for blood levels of leukocytes, lymphocytes, or neutrophils.
  • Considered by the Investigator to be immunocompromised based on medical history, physical examination, laboratory testing, or any other testing required by local guidelines, or due to prior immunosuppressive or immunomodulating treatment.
  • Subjects for whom magnetic resonance imaging (MRI) is contraindicated (i.e., have pacemakers or other contraindicated implanted metal devices, are allergic to gadolinium, or have claustrophobia that cannot be medically managed).
  • History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal, or other major disease that would preclude participation in a clinical study.
  • History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
  • Known history of or positive test result for Human Immunodeficiency Virus (HIV).
  • Positive test result for hepatitis C virus (test for hepatitis C virus antibody [HCV Ab]) or hepatitis B virus (test for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]).
  • History of transplantation or any anti-rejection therapy.
  • Presence of any infectious disease (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to screening.
  • History of progressive multifocal leukoencephalopathy (PML) or other opportunistic infections.

Treatment History (Part 1)

  • Any prior treatment with cell-depleting therapies, including total lymphoid irradiation, cladribine, rituximab, alemtuzumab, or bone marrow ablation.
  • Any prior treatment with natalizumab.
  • Treatment with mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, T cell or T cell receptor vaccination, fingolimod, daclizumab, or cytapheresis within 6 months prior to randomization.
  • Treatment with intravenous or oral corticosteroids, intravenous immunoglobulin (IVIg), or plasmapheresis for treatment of multiple sclerosis within the 3 months prior to randomization.
  • Treatment with glatiramer acetate or any interferon beta preparations within 4 weeks prior to randomization.
  • Treatment with 4-aminopyridine within 30 days prior to randomization, unless a stable dose has been maintained for at least 30 days prior to randomization and will be continued for the course of this study.

Inclusion Criteria (Part 2):

•Subjects must have participated in and completed Part 1 per protocol, and have documented assessment attempts for Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT) prior to first open-label dosing.

Exclusion Criteria (Part 2):

  • Subjects with any significant change in clinical status, including laboratory tests that, in the opinion of the Investigator, would make them unsuitable to participate in this extension study. The Investigator must re-review the subject's medical fitness for participation and consider any diseases that would preclude treatment.
  • Subjects who discontinued study treatment in Part 1 OR had fewer than 20 infusions in Part 1 OR missed 2 or more consecutive infusions in Part 1.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01416181

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Sponsors and Collaborators
Biogen Idec
  More Information

Additional Information:
No publications provided

Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT01416181     History of Changes
Other Study ID Numbers: 101MS326, EUDRA CT No: 201-0-021978-11
Study First Received: July 21, 2011
Last Updated: September 12, 2013
Health Authority: Israel: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Spanish Agency for Medicines and Health Products
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Ireland: Irish Medicines Board
United States: Institutional Review Board
Czech Republic: State Institute for Drug Control
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Sweden: Medical Products Agency
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Finland: Finnish Medicines Agency
Germany: Paul-Ehrlich-Institut
Russia: Ministry of Health of the Russian Federation
Italy: Italian Medicines Agency

Keywords provided by Biogen Idec:
Natalizumab
secondary
multiple sclerosis
MS
SPMS
Tysabri

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Chronic Progressive
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 22, 2014