An Open-label, Multicenter, Extension Study to Evaluate the Safety and Tolerability of Natalizumab Following Re-Initiation of Dosing in Multiple Sclerosis Subjects Who Have Completed Study C-1801 or C-1802 and a Dosing Suspension Safety Evaluation - STRATA

• Register: EUCTR
• Last refreshed on: 4 April 2022
• Main ID: EUCTR2005-004061-41-GR
• Date of registration: 28/07/2006
• Prospective Registration: Yes
• Primary sponsor: BIOGEN IDEC LTD
• Public title: An Open-label, Multicenter, Extension Study to Evaluate the Safety and Tolerability of Natalizumab Following Re-Initiation of Dosing in Multiple Sclerosis Subjects Who Have Completed Study C-1801 or C-1802 and a Dosing Suspension Safety Evaluation - STRATA
• Scientific title: An Open-label, Multicenter, Extension Study to Evaluate the Safety and Tolerability of Natalizumab Following Re-Initiation of Dosing in Multiple Sclerosis Subjects Who Have Completed Study C-1801 or C-1802 and a Dosing Suspension Safety Evaluation - STRATA
• Date of first enrolment: 31/10/2006
• Target sample size: 900
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-004061-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, Denmark, Finland, Germany, Greece, Hungary, Ireland, Italy, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1) must give written informed consent and provide all authorizations required by local law
2) must be an MS subject who completed Study C-1801 or C-1802 and completed a Dosing Suspension Safety Evaluation (neurological examination and an magnetic resonance imaging scan)
3) must be considered by the Investigator to be free of signs and symptoms suggestive of PML based on medical history, physical examination, or laboratory testing
4) must be willing to discontinue and remain free from concomitant immunosuppressive or immunomodulatory treatment (including IFNb and GA) for the duration of the study.

NOTE: Subjects who were found to be on placebo after being unblinded for a serious adverse event (SAE) in Study C-1801 or C-1802 are eligible to enroll in this study if they completed a Dosing Suspension Safety Evaluation, receive approval from the Biogen Idec Medical Director or the relevant Advisory Committee, meet all other inclusion criteria for this study, and are not excluded based on the exclusion criteria for this study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Medical History
1. considered by the Investigator to be immunocompromised, based on medical history, physical examination, or laboratory testing (results from the Dosing Suspension Safety
Evaluation from Study C-1808 may be used), or due to prior immunosuppressive treatment
2. history of persistent anti-natalizumab antibodies, based upon testing from prior
natalizumab studies
3. history of, or available abnormal laboratory results indicative of, any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric (including major depression), renal, and/or other major disease that would preclude the administration of a recombinant humanized antibody immunomodulating agent for 48 weeks. The Investigator must re-review the subject’s medical fitness for participation and consider any diseases that would preclude treatment.
4. history of malignancy (subjects with basal cell carcinoma that has been completely excised prior to study entry remain eligible)
5. known history of human immunodeficiency virus infection or hematological malignancy
6. history of organ transplantation (including anti-rejection therapy)
7. history of severe allergic or anaphylactic reactions or known drug hypersensitivity
8. a significant change (as determined by the Investigator) in the subject’s medical history from their previous natalizumab study
9. a clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to the Screening Visit in Study 101-MS-321

Treatment History
10. discontinued natalizumab in a previous study due to allergic reaction or any other SAE considered to be related to natalizumab treatment
11. discontinued study drug in Study C-1801 or C-1802 because of an AE or due to reasons other than significant disease progression (as defined in the C-1801 and C-1802 protocols)
12. treatment with immunosuppressant medications (e.g., mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate) within 3 months prior to Screening

Miscellaneous
13. female subjects who are not postmenopausal for at least 1 year, surgically sterile does not include tubal ligation), or willing to practice effective contraception (as defined by the Investigator) during the study
14. women who are breastfeeding, pregnant, or planning to become pregnant while on study
15. current enrollment in any other study treatment or disease study
16. unwillingness or inability to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the study protocol
17. other unspecified reasons that, in the opinion of the Investigator and/or Biogen Idec, make the subject unsuitable for enrolment into this study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple sclerosis (MS)
MedDRA version: 8.1 Level: LLT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis

Intervention(s)

Trade Name: TYSABRI®
Product Name: NATALIZUMAB
Product Code: BG00002
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Natalizumab
Current Sponsor code: BG00002
Other descriptive name: Recombinant humanized anti-alpha 4 integrin antibody
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

Main Objective: To further evaluate the safety of natalizumab monotherapy by:
1) evaluating the risk of hypersensitivity and immunogenicity following re-exposure to natalizumab, and
2) confirming the safety of switching from interferon beta (IFNb), glatiramer acetate (GA), or other MS therapies to natalizumab.

Primary end point(s): The primary objectives of this study are to further evaluate the safety of natalizumab monotherapy by evaluating the risk of hypersensitivity and immunogenicity following re-exposure to natalizumab, and confirming the safety of switching from IFNb, GA, or other MS therapies to natalizumab. All analyses will be based upon observed data, no imputation methods will be used for missing data.

The safety endpoint under consideration will be the incidence of AEs. The incidence of development of antibodies to natalizumab will also be assessed.

Secondary Objective: To explore:
1) the feasibility of a methodology for early detection and differentiation of progressive multifocal leukoencephalopathy (PML) from MS in subjects who develop new neurological symptoms or signs while on natalizumab therapy
2) whether serial blood testing can be used for monitoring the presence of JC virus in the MS population, and
3) an approach to testing for persistent anti-natalizumab antibodies.

Secondary ID(s)

101-MS-321

2005-004061-41-GB

Ethics review

Status: Approved
Approval date: 31/10/2006
Contact:

Results

• Results available: Yes
• Date Posted: 07/05/2015
• Date Completed: 30/04/2014
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-004061-41/results