Phase 2
N=231
Ofatumumab Subcutaneous Administration in Subjects With Relapsing-Remitting Multiple Sclerosis
Multiple Sclerosis
Bottom Line
View on ClinicalTrials.gov: NCT01457924 ↗Enrolled (actual)
231
Serious AEs
2.6%
Results posted
Mar 2018
Primary outcome: Primary: Cumulative Number of New Gadolinium-enhancing (GdE) T1 Lesions at Week 12 — 4.2; 1.7; 2.2; 2.2 Cumulative number of lesions — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Ofatumumab 3mg (Drug); Ofatumumab 30mg (Drug); Ofatumumab 60mg (Drug); Placebo (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Aug 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cumulative Number of New Gadolinium-enhancing (GdE) T1 Lesions at Week 12 |
4.2; 1.7; 2.2; 2.2; 1.2 | <0.001 sig |
| SECONDARY Cumulative Number of New GdE T1 Lesions at Week 24 |
5.6; 2.2; 2.5; 2.2; 1.4 | 0.003 sig |
| SECONDARY Change From Baseline in Brain Volume at Week 24 and Week 48 |
-13.5; -7.2; -8.4; -13.3; -1.4; -22.0 | — |
| SECONDARY Cumulative Number of Persistent GdE Brain Lesions on T1-weighted MRI at Week 12 |
3.2; 1.2; 2.3; 1.8; 1.8 | — |
| SECONDARY Cumulative Number of All (New Plus Persistent) GdE Brain Lesions on T1-weighted MRI at Week 12 |
7.4; 2.9; 4.5; 4.0; 3.1 | <0.001 sig |
| SECONDARY Total Volume of New GdE Brain Lesions on T1-weighted MRI at Week 12 |
607.5; 226.5; 452.9; 248.6; 146.6 | 0.026 sig |
| SECONDARY Total Volume of All (New and Persistent) GdE Brain Lesions on T1-weighted MRI at Week 12 |
1039.6; 386.2; 886.2; 426.5; 344.4 | 0.004 sig |
| SECONDARY Cumulative Number of New and Newly Enlarging GdE T2 Lesions at Week 12 |
3.7; 1.2; 1.6; 1.7; 0.8 | <0.001 sig |
| SECONDARY Total Volume of New and/or Newly Enlarging T2 Lesions at Week 12 |
1204.5; 279.9; 611.3; 293.8; 167.9 | — |
| SECONDARY Cumulative Number of New T1 Hypointense Lesions at Week 24 and Week 48 |
0.4; 0.4; 0.5; 0.5; 0.3; 0.6 | — |
| SECONDARY Cumulative Volume of New T1 Hypointense Lesions at Week 24 and Week 48 |
86.9; 43.1; 67.4; 65.0; 42.9; 113.6 | — |
Summary
Ofatumumab is a novel Immunoglobulin 1ĸ ( IgG1ĸ) lytic monoclonal antibody (mAb) that specifically binds to the human Cluster of Differentiation 20 (CD20) antigen of which expression is restricted to B lymphocytes from the pre-B cell stage to the plasmacytoid immunoblast stage only. A recent trial with an anti-CD20 mAb (rituximab) demonstrated that targeting B-cells reduces the number of gadolinium-enhancing (GdE) T1 lesions and the relapse rate in relapsing-remitting multiple sclerosis (RRMS). Ofatumumab has been shown to be both well tolerated and efficacious in several indications, including a small, placebo-controlled trial in RRMS using an intravenous (IV) formulation.
This double-blind, placebo-controlled, parallel-group study will investigate the safety and efficacy of a subcutaneous formulation of ofatumumab in the treatment of subjects with RRMS. The primary objective of the study is to investigate the efficacy as assessed by magnetic resonance imaging. Other objectives will include evaluation of tolerability/safety, dose-response relationship, pharmacokinetics, pharmacodynamics, exposure-response, as well as other clinical endpoints.
Eligibility 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 2 years without menses. Female subjects who are post-menopausal 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 QT interval for heart rate corrected using Bazett's Formula (QTcB) or QT interval for heart rate corrected using Fridericia's Formula (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) screening for John Cunningham (JC) Virus as measured by plasma John Cunningham Virus (JCV) DNA.
- Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
- Prior history, or suspicion, of tuberculosis (TB)
- Known history of positive serology for HIV.
- Any of the following screening laboratory values:
- White blood cells (WBC) 2.0 times the upper limit of normal
- Aspartate aminotransferase (AST) >2.0 times the upper limit of normal
- Alkaline phosphatase (ALP) >1.5
Data sourced from ClinicalTrials.gov (NCT01457924). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.