Clinical trial NCT02142205: Safety and Efficacy of Natalizumab (BG00002, Tysabri®) in Russian Participants With Relapsing Remitting Multiple Sclerosis (RRMS)
Official title: A Prospective, Open-label, Non-randomized, Clinical Trial to Evaluate the Safety and Efficacy in RUSsian RRMS Patients on One Year Treatment With Natalizumab (TYSabri®).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Relapsing-Remitting Multiple Sclerosis
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2014-05-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective is to evaluate the safety and tolerability of natalizumab (BG00002, Tysabri®) in the study population (Russian participants with relapsing remitting multiple sclerosis). The secondary objectives are to look at evaluation of severity of relapse, hospitalization and steroid use requirement; Expanded Disability Status Scale (EDSS), functional tests, quality of life self-assessment questionnaires including the short form health survey self-assessment questionnaire (SF-36) and multiple sclerosis impact scale 29 (MSIS-29), evidence of MRI disease activity, participants free of disease activity (clinical activity and/MRI activity) and anti JC Virus (JCV) antibody evaluation.


Eligibility criteria: Key Inclusion Criteria:

* Must be natalizumab naïve.
* Must have a documented diagnosis of a relapsing remitting form of MS as defined by the revised McDonald Committee criteria (Polman et al., 2011)
* Must have had at least 1 relapse in the previous year:
* Must be stable in disability for at least 30 days prior to enrollment to the study
* Must be stable in symptomatic management of the disease, specifically spasticity, depression and fatigue for at least 30 days prior to enrollment to the study.
* Must be considered by the Investigator to be free of signs and symptoms suggestive of Progressive multifocal leukoencephalopathy (PML) based on medical history, physical examination, or laboratory testing.
* Must be willing to discontinue and remain free from concomitant immunosuppressive or immunomodulatory treatment (including IFN-beta and Glatiramer Acetate) while being treated with natalizumab during the study.

Key Exclusion Criteria:

Medical History:

* Onset of a relapse within 50 days prior to first infusion.
* Considered by the Investigator to be immunocompromised, based on medical history, physical examination, or laboratory testing or due to prior immunosuppressive treatment
* History of, or available abnormal laboratory results indicative of, any significiant viral, 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. The Investigator must re-review the subject's medical fitness for participation and consider any diseases that would preclude treatment.
* History of malignancy (subjects with basal cell carcinoma that has been completely excised prior to study entry remain eligible)
* Known history of human immunodeficiency virus infection or hematological malignancy
* History of organ transplantation (including anti-rejection therapy)
* A clinically significant infectious illness (e.g. abscess, pneumonia, septicemia) within 30 days prior to the Screening Visit.

Treatment History:

- Treatment with any kind of immunosuppressant medications (e.g., mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate, fingolimod, cladribine) within 6 months prior to Screening

Miscellaneous:

* Female subjects who are not postmenopausal for at least 1 year, surgically sterile (does not include tubal ligation), or unwilling to practice effective contraception (as defined by the Investigator) during the study
* Women who are breastfeeding, pregnant, or planning to become pregnant while on study
* Other unspecified reasons that, in the opinion of the Investigator and/or Biogen Idec, make the subject unsuitable for enrollment into this study.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Number of participants that experience Serious Adverse Events (SAEs) and adverse events (AEs)
timeFrame: Up to Week 52
Secondary outcomes:
measure: Annualized relapse rate (ARR)
timeFrame: Up to Week 52
measure: Time course to first relapse
timeFrame: Up to Week 52
measure: Severity of relapse as measured by the Number of relapses requiring hospitalization and the Number of relapses requiring steroid treatment
timeFrame: Up to Week 52
measure: Number of participants that do not experience a relapse
timeFrame: Up to Week 52
measure: Change in EDSS scores
timeFrame: Up to Week 48
measure: Duration of time to progression as measured by EDSS score
timeFrame: Up to Week 48
measure: Number of participants that do not experience a progression in EDSS score
timeFrame: Up to Week 48
measure: Percentage of participants with improvement in EDSS scores
timeFrame: Up to Week 48
measure: Changes from baseline in nine hole peg test (9HPT)
timeFrame: Up to Week 48
measure: Changes in Timed 25 foot walk from baseline
timeFrame: Up to Week 48
measure: Changes in cognition as assessed by the Symbol digit modalities test (SDMT)
timeFrame: Up to Week 48
measure: Changes from baseline in visual function test (VFT)
timeFrame: Up to Week 48
measure: Impact on participants quality of life using SF-36 and MSIS-29 self-assessment questionnaires
timeFrame: Up to Week 48
measure: Percentage of participants that do not experience a relapse or progression in EDSS score
timeFrame: Month 12
measure: Number of T1 gadolinium (Gd) enhancing lesions
timeFrame: At Week 48
measure: Number of new T2 hyper intense lesions
timeFrame: At Week 48
measure: Number of newly enlarging T2 hyper intense lesions
timeFrame: At Week 48
measure: Number of new hypo intense T1 lesions (black holes)
timeFrame: At Week 48
measure: Number of conversion of Gd lesions into black holes
timeFrame: At Month 12
measure: Percentage of participants that do not experience a relapse as measured by an EDSS score that is not indicative of progression
timeFrame: At Month 12
measure: Percentage of participants that do not develop new GD+ and new or newly enlarging T2 hyper intense lesions
timeFrame: At Week 48
measure: Proportion of participants free of disease activity: no clinical & no MRI activity
timeFrame: Up to Week 48
measure: Number of participates that are Anti JCV antibody positive at baseline
timeFrame: At Baseline
Other outcomes:
Locations:
city: Belgorod
country: Russian Federation
facility: Research Site
city: Kaluga
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Krasnodar
country: Russian Federation
facility: Research Site
city: Kursk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Rostov-on-Don
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Smolensk
country: Russian Federation
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: