Ofatumumab Subcutaneous Administration in Subjects With Relapsing-Remitting Multiple Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 28 January 2013
• Main ID: NCT01457924
• Date of registration: 20/10/2011
• Primary sponsor: GlaxoSmithKline
• Public title: Ofatumumab Subcutaneous Administration in Subjects With Relapsing-Remitting Multiple Sclerosis MIRROR
• Scientific title: A Randomized, Double-blind, Placebo-controlled, Parallel-Group, Dose-Ranging Study to Investigate the MRI Efficacy and Safety of Six Months' Administration of Ofatumumab in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS)
• Date of first enrolment: July 2010
• Target sample size: 196
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01457924
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Countries of recruitment

Bulgaria, Canada, Czech Republic, Denmark, Germany, Italy, Netherlands, Norway, Russian Federation, Spain, United States

Contacts

• Name: US GSK Clinical Call Center

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Able to provide signed, written informed consent to participate in the study

- 18-55 years of age.

- Definite diagnosis of MS according to the 2010 revisions of the McDonald diagnostic
criteria for MS [Polman, 2011].

- Subjects do not have any manifestation of another type of MS other than RRMS.

- Subjects must have a relapsing-remitting course of disease with at least one of the
following prior to screening:

- At least one confirmed relapse within the previous year or

- At least two confirmed relapses within the previous 2 years or

- At least one relapse in the previous 2 years, with a GdE brain lesion on an MRI scan
in the past year.

- Expanded Disability Status Scale (EDSS) score of 0-5.5 (inclusive) at screening.

- Neurologically stable with no evidence of relapse for at least 30 days prior to start
of Screening and during the Screening Phase (subjects who relapse during the
screening Phase can be re-screened, once the relapse has resolved).

- A female subject is eligible to enter the study if she is:

- Of non-childbearing potential

- Of childbearing potential and NOT pregnant or nursing, has a negative serum pregnancy
test at screening, and agrees to one of the following:

- Complete abstinence from intercourse for the period from consent into the study until
6 months after the last dose of investigational product; or,

- Consistent and correct use of one of the following acceptable methods of birth
control for the period from consent into the study until 6 months after the last dose
of investigational product:

Oral contraceptives (either combined or progesterone only) Injectable progesterone
Levonorgestrel implants Estrogenic vaginal ring Percutaneous contraceptive patches
Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of
<1% per year Male partner sterilization (vasectomy with documentation of azoospermia)
prior to the female subject's entry into the study; this male must be the sole partner for
the subject Double barrier method: condom and an occlusive cap (diaphragm or
cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository).

A female is considered "Non-childbearing potential" if she is status-post hysterectomy,
status-post surgical removal of both ovaries, has current, documented tubal ligation, or
is postmenopausal and >2 years without menses. Female subjects who are post-menopausal <2
years must be confirmed menopausal by Follicle Stimulating Hormone (FSH) and estradiol
levels.

A female is considered "childbearing potential" if she has functional ovaries, ducts, and
uterus with no impairment that would cause sterility. This includes women with
oligomenorrhea (even severe), and women who are perimenopausal or who have just begun to
menstruate.

- French subjects: In France, a subject will be eligible for inclusion in this study
only if either affiliated to, or a beneficiary of, a social security category.

Exclusion Criteria:

- Unable to undergo MRI scans (e.g. due to pacemaker, severe claustrophobia,
hypersensitivity to contrast media, or who lack adequate peripheral venous access).

- Any clinically significant brain abnormality other than MS found on MRI.

- Neurological findings consistent with Progressive Multifocal Leukoencephalopathy
(PML) or confirmed PML (see Appendix 4, Section 11.4, for PML monitoring algorithm).

- Subjects whom experience a relapse during the Screening Phase. These subjects may be
eligible for re-screening after consultation with GSK.

- History of clinically significant CNS trauma (e.g. traumatic brain injury, cerebral
contusion, spinal cord compression) or a history or presence of myelopathy due to
spinal cord compression by disk or vertebral disease.

- Prior treatment with any of the following:

- Systemic glucocorticoids or Adrenocorticotrophic hormone (ACTH) within one month
prior to screening

- Receipt of a live vaccine within 6 weeks prior to screening

- Glatiramer acetate (Copaxone) or IFN-ß (Betaferon, Betaseron, Avonex, or Rebif)
within 3 months prior to screening

- Any immunomodulatory therapies, excluding glatiramer acetate or IFN-ß, within 6
months prior to screening including natalizumab and fingolimod (Gilenya),
immunoglobulin, or plasma exchange/plasmapheresis

- Any monoclonal antibodies at any time, other than natalizumab (Tysabri)

- Any lymphocyte-depleting therapies, including, but not limited to: cladribine,
anti-CD4, total body irradiation, or bone marrow transplantation

- Any immunosuppressive agents, including, but not limited to: mitoxantrone,
azathioprine, cyclosporine, cyclophosphamide, or tacrolimus

- Past or current history of medically significant adverse effects (including allergic
reactions) from:

- Cetirizine (or equivalent)

- Paracetamol/acetaminophen

- Corticosteroids

- Known hypersensitivity to components of the investigational product.

- Past or current malignancy, except for

- Cervical carcinoma Stage 1B or less

- Non-invasive basal cell and squamous cell skin carcinoma

- Cancer diagnoses with a duration of complete response (remission) >5 years

- A history of hematologic malignancy excludes a subject from participation, regardless
of response.

- Electrocardiogram (ECG) showing a clinically significant abnormality at Screening or
showing an average QTcB or QTcF interval >/=450 msec (>/=480 msec for subjects with
a Bundle Branch Block) over 3 consecutive ECGs.

- Significant concurrent, uncontrolled medical condition including, but not limited to,
cardiac, renal, hepatic, hematological, gastrointestinal, endocrine, immunodeficiency
syndrome, pulmonary, cerebral, psychiatric, or neurological disease which in the
opinion of the investigator could affect the subject's safety, impair the subject's
reliable participation in the trial, impair the evaluation of endpoints, or
necessitate the use of medication not allowed by this protocol.

- History of severe, clinically significant CNS trauma (e.g. cerebral contusion, spinal
cord compression) or a history or presence of myelopathy due to spinal cord
compression by disk or vertebral disease.

- Chronic or ongoing active infectious disease requiring long term systemic treatment
such as, but not limited to, chronic renal infection, chronic chest infection with
bronchiectasis, tuberculosis, or active hepatitis C.

- Previous serious opportunistic or atypical infections.

- Positive polymerase chain reaction (PCR) s


Age minimum: 18 Years
Age maximum: 55 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Multiple Sclerosis

Intervention(s)

Drug: Ofatumumab 30mg

Drug: Ofatumumab 3mg

Drug: Ofatumumab 60mg

Drug: Placebo

Primary Outcome(s)

Cumulative number of new T1 Gadolinium Enhancing (GdE) brain lesions [Time Frame: 12 weeks]

Secondary Outcome(s)

Change from Screen in brain volume [Time Frame: 48 weeks]

Change in volume of T1 hypointense lesions [Time Frame: 48 weeks]

Cumulative number of all Gd-enhancing brain lesions on T1-weighted MRI [Time Frame: 12 weeks]

Cumulative number of new and/or newly enlarging T2 lesions [Time Frame: 12 weeks]

Cumulative number of new T1 GdE brain lesions [Time Frame: 24 weeks]

Cumulative number of new T1 hypointense lesions [Time Frame: 48 weeks]

Cumulative number of persistent Gd-enhancing brain lesions on T1-weighted MRI [Time Frame: 12 weeks]

Total volume of all Gd-enhancing brain lesionos on T1-weighted MRI [Time Frame: 12 weeks]

Total volume of new Gd-enhancing brain lesions on T1-weighted MRI [Time Frame: 12 weeks]

Volume of new and/or newly enlarging T2 lesions [Time Frame: 12 weeks]

Secondary ID(s)

112831

Source(s) of Monetary Support

Please refer to primary and secondary sponsors