A Single Arm Study Evaluating the Efficacy, Safety and Tolerability of Ofatumumab in Patients With Relapsing Multiple Sclerosis

A Single-arm, Prospective, Multi-center Study to Explore Maintained Efficacy With Ofatumumab Therapy in Patients With Relapsing Multiple Sclerosis Who Discontinue Intravenously Delivered Anti-CD20 Monoclonal Antibody (aCD20 mAb) Therapy (OLIKOS)

ClinicalTrials.gov Identifier: NCT04486716

Novartis Reference Number: COMB157GUS07

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

A single arm study evaluating the continued efficacy, safety and tolerability of ofatumumab in patients with relapsing multiple sclerosis who are transitioning from aCD20 mAb therapy

Condition 
Relapsing Multiple Sclerosis
Phase 
Phase 3
Overall status 
Not yet recruiting
Enrollment count 
100 participants
Start date 
Sep 30, 2020
Completion date 
Apr 29, 2022
Gender 
All
Age(s)
18 Years - 55 Years (Adult)

Interventions

Drug
Ofatumumab
Investigational drug will be provided in an autoinjector for subcutaneous administration containing 20 mg ofatumumab (20 mg/0.4 ml)

Eligibility Criteria

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

Written informed consent must be obtained before any assessment is performed.
Male or female participants aged 18 to 55 years (inclusive) at screening.
Diagnosis of relapsing MS (RMS) according to the 2017 Revised McDonald criteria (Thompson et al.

2018), including CIS, RRMS or SPMS with disease activity as defined by (Lublin et al. 2014).

4. Disability status at Screening with an EDSS score of 0 to 5.5 (inclusive). 5. Received at least 2 but no more than 5 courses of intravenous aCD20 mAb (loading doses are considered 1 course):

• Participants currently treated with ocrelizumab must have received (meet all three criteria below):

2 fully infused initial 300 mg ocrelizumab iv infusions
From 1 to 4 fully infused 600 mg ocrelizumab iv infusions 6 months (+/- one month)
Last fully infused ocrelizumab dose must have occurred within 4-9 months prior to baseline

Participants currently treated with rituximab must have received (meet both criteria below):

At least 2, but no more than 5, fully infused courses of rituximab 500 mg - 1000 mg iv every 6 months (+/- one month).

a. Initial loading regimens of rituximab i.e. 500 mg - 1000 mg on day 1 and on day 15, are allowed but this is consider a single course and must be followed by additional infusion(s) every 6 months (+/- one month)

Last fully infused rituximab dose must have occurred within 4-9 months prior to baseline.

6. Participants discontinuing aCD20 therapy for reasons including, but not limited to: physician/participant preference, access to commercial drug (e.g. insurance coverage issues) or for other logistical reasons (such as geographical relocation, travel, etc.) are eligible for this study. 7. Participants with CD19 B cells that are depleted to < 1% of the participant's baseline CD19 B cell concentration. 8. Neurologically stable within 1 month prior to first study drug administration. 9. Must be able to use a smart device or have a caregiver that can assist.

Exclusion Criteria:

Participants meeting any of the following criteria are not eligible for inclusion in this study:

Participants that have demonstrated suboptimal response to aCD20 therapy to include: documented relapse while on previous aCD20 treatment, or signs of MRI activity, defined as ≥ 2 active Gd+ T1 lesions, or any new or newly enlarging T2 lesions, or any signs of clinical worsening as measured by EDSS or any clinical measure, documented within the last 6 months.

Discontinuing aCD20 mAb therapy due to the following treatment- emergent adverse events:

Severe infusion-related reactions (Grade 3 or above)
Recurrent infections defined as ≥ 2 severe infections or ≥ 3 respiratory infections or the need for ≥ 2 courses of antibiotics since starting aCD20 therapy
Decreased IgG requiring treatment with Intravenous immunoglobulin
Participants with primary progressive MS (Polman et al 2011) or SPMS without disease activity (Lublin et al 2014).
Participants meeting criteria for neuromyelitis optica (Wingerchuk et al 2015).
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 6 months after stopping study medication. Highly effective contraception methods include:

Total abstinence
Female sterilization
For female participants on the study, the vasectomized male partner should be the sole partner
Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.

Participants with active chronic disease (or stable but treated with immune therapy) of the immune system other than MS (e.g.

rheumatoid arthritis, scleroderma, Sjögren's syndrome, Crohn's disease, ulcerative colitis, etc.) or with immunodeficiency syndrome (hereditary immune deficiency, drug-induced immune deficiency).

Participants with active systemic bacterial, viral or fungal infections, or known to have acquired immunodeficiency syndrome (AIDS).
Participants with neurological symptoms consistent with PML or with confirmed PML.

Participants at risk of developing or having reactivation of syphilis or tuberculosis (eg. Participants with known exposure to, or history of syphilis, or active or latent tuberculosis, even if previously treated).

Testing for syphilis and tuberculosis will be done at Screening. Testing must be done by the central lab (for syphilis e.g. by positive rapid plasma reagin (RPR); for tuberculosis testing, QuantiFERON®-TB Gold test to assess participant's eligibility at Screening).

Participants at risk of developing or having reactivation of hepatitis:

Positive results at Screening for serological markers for hepatitis (H)

A, B, C, and E indicating acute orpchronic infection:

anti-HA Immunoglobulin M (IgM)
HBs Ag and/or anti-HBc IgM and/or HB virus deoxyribonucleic acid (DNA)
anti-HBs negative and Anti-HBc positive
anti-HC IgG (if positive IgG, HCV-RNA PCR will be performed and if negative, participant can be enrolled)
anti-HE IgM (if positive IgG and/or IgM, perform HE-RNA PCR and if negative, participant can be enrolled) NOTE: If the Investigator suspects false positive hepatitis serology results, such as an antibody pattern indicating acute hepatitis infection but no corresponding elevated liver enzymes and no signs or symptoms of liver disease, an infectious disease expert may be consulted. If the infectious disease expert finds no evidence of acute or chronic hepatitis infection and considers the serology results false positive and not clinically relevant, the Investigator must document (in source data and as a comment in the eCRF) that the serology results are considered false positive and may then enroll the participant.
Have received any live or live-attenuated vaccines (including for varicella-zoster virus or measles) within 2 months prior to first study drug administration.

Have been treated with any of the medications listed below within the time specified Medication Exclusionary if used within the timeframe specified below Intravenous, oral, intra-articular or intramuscular corticosteroids, adrenocorticotropic hormone exclusionary within 30 days prior to Screening MRI scan

Immunosuppressive, chemotherapeutic medications (e.g. natalizumab, mitoxantrone, cyclophosphamide, cladribine, S1P modulators) exclusionary within 2 years prior to first study drug administration

Mitoxantrone (with evidence of cardiotoxicity following treatment or cumulative life-time dose > 60mg/m2) Alemtuzumab Lymphoid irradiation; bone marrow transplantation Other strongly immunosuppressive treatments (with effects potentially lasting over 6 months), Ofatumumab, aCD20+ monoclonal antibodies in development (e.g. ublituximab or obinutuzumab) and Daclizumab exclusionary if taken Anytime

Use of other investigational drugs at the time of enrollment (Screening) or within the prior 30 days, or five elimination half-lives, or until the expected pharmacodynamic effect has returned to baseline, whichever is longer.
History of malignancy of any organ system (other than basal cell carcinoma, in situ squamous cell carcinoma of skin, or in situ carcinoma of cervix or the uterus that have been radically treated e.g. completely excised with clear margins), within the past 5 years, regardless of whether or not there is evidence of local recurrence or metastases.

Any of the following conditions or treatments that may impact the safety of the participant:

History of, or current, significant cardiac disease including cardiac failure (NYHA functional class II-IV), myocardial infarction (within 6 months), unstable angina (within 6 months), transient ischemic attack (within 6 months), stroke, cardiac arrhythmias requiring treatment or uncontrolled arterial hypertension
Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia and clinically significant second or third degree AV block without a pacemaker on screening electrocardiogram (ECG)
History of or active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis
Participants with asthma requiring regular treatment with oral steroids
Severe hepatic impairment (Child-Pugh class C) or any chronic liver or biliary disease
Participants with severe renal impairment (Glomerular Filtration Rate < 30 ml/min/1.73 m2)
Any medically unstable condition as determined by the Investigator

Any of the following abnormal laboratory values as confirmed by the central laboratory prior to first study drug administration:

Total or conjugated bilirubin (BIL) greater than 3 times upper limit of normal (ULN) range, unless in the context of Gilbert's syndrome
Alkaline phosphatase (ALP) greater than 5 times the ULN range
ALT between 1.5 and 5 times the ULN range and an active infection with hepatotropic viruses (Herpes simplex virus, Cytomegalovirus and Epstein-Barr Virus)
Serum IgG < 300mg/dL (according to central laboratory range) Any other clinically significant laboratory assessment as determined by the Investigator (e.g. significant anemia, neutropenia, thrombocytopenia, signs of impaired bone marrow function)
Participants with severe hypoproteinaemia e.g. in nephrotic syndrome.

Participants with any of the following neurologic/psychiatric disorders prior to first study drug administration:

• Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the Columbia- Suicide Severity Rating Scale (C-SSRS), if this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.

History of hypersensitivity to any of the study drugs or excipients (including rare hereditary problems of galactose intolerance, Lapp lactase deficiency and glucose-galactose malabsorption) or to drugs of similar chemical classes.

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
Email: 

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