Clinical trial NCT04486716: A Single Arm Study Evaluating the Efficacy, Safety and Tolerability of Ofatumumab in Patients With Relapsing Multiple Sclerosis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsing Multiple Sclerosis
Keywords: Ofatumumab
Relapsing multiple sclerosis
MS
RMS
CIS
RRMS
SPM
ocrelizumab
MRI
CD19 B
adult,
OMB157
open-label
rituximab
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-07-27
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: This is a single-arm multi-center, study in approximately 100 participants with relapsing multiple sclerosis who were previously treated with aCD20 mAb therapy. Eligible participants will receive open label ofatumumab 20 mg subcutaneous monthly for 12 months following initial loading regimen of 20 milligrams subcutaneous doses on Days 1, 7 and 14. Assessments will include but are not limited to Magnetic Resonance Imaging (MRI) assessed for quality by central reading center, multiple Patient Reported Outcome measurements and safety assessments. Participants that do not continue onto commercial ofatumumab or another therapy within one month of the End of Study Visit must continue into the safety Follow Up phase, consisting of every 3 month visits including B cell monitoring until they are able to start on commercial ofatumumab or switch to another therapy or until their B cells are repleted defined as a B cell concentration greater than the individual participant's baseline value or greater than the lower limit of normal. All participants will have a safety follow-up phone call at 30 days post study.

Eligibility criteria: Inclusion Criteria:

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

1. Written informed consent must be obtained before any assessment is performed.
2. Male or female participants aged 18 to 60 years (inclusive) at screening.
3. 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 courses of intravenous aCD20 mAb (loading doses are considered 1 course):

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

1. 2 fully infused initial 300 mg ocrelizumab iv infusions 2. At least 1 fully infused 600 mg ocrelizumab iv infusions 6 months (+/- one month) 3. 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):

1. At least 2 fully infused courses of rituximab 500 mg - 1000 mg iv every 6 months (+/- one month).

   1. 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)
2. 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. Neurologically stable within 1 month prior to first study drug administration.

8. 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:

1. Participants that have demonstrated suboptimal response to aCD20 therapy to include:

   a. Signs of MRI activity, defined as ≥ 2 active Gd+ T1 lesions, or any new or newly enlarging T2 lesions, documented within the past 6 months
   * If a prior MRI within the last 6 months is not available, then new or newly enlarging T2 lesions should be considered "not documented" and the patient may continue screening b. Documented relapse while on stable, previous aCD20 treatment.
   * Relapses during the first 3 months of intravenous aCD20 therapy are allowable if the participant is then relapse-free for the 12 months following the relapse while on intravenous aCD20 therapy c. Any signs of clinical worsening as measured by EDSS or any clinical measure documented within the last 6 months
2. Discontinuing aCD20 mAb therapy due to the following treatment- emergent adverse events:

   1. Severe infusion-related reactions (Grade 3 or above)
   2. Recurrent infections defined as ≥ 2 severe infections or ≥ 3 respiratory infections or the need for ≥ 2 courses of antibiotics since starting aCD20 therapy, if the Investigator believes this is related to therapy.
   3. Decreased IgG requiring treatment with Intravenous immunoglobulin
3. Participants with primary progressive MS (Polman et al 2011) or SPMS without disease activity (Lublin et al 2014).
4. Participants meeting criteria for neuromyelitis optica (Wingerchuk et al 2015).
5. Pregnant or nursing (lactating) women
6. 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.
7. 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).
8. Participants with active systemic bacterial, viral or fungal infections, or known to have acquired immunodeficiency syndrome (AIDS).
9. Participants with neurological symptoms consistent with PML or with confirmed PML.
10. Participants at risk of developing or having reactivation of syphilis or tuberculosis
11. Participants at risk of developing or having reactivation of hepatitis.
12. Have received any live or live-attenuated vaccines (including for varicella-zoster virus or measles) within 4 weeks prior to first study drug administration. a. There is presently no contraindication for the use of an inactivated, viral-vector-or mRNA based Sars-CoV-2 vaccine in patients who are immunocompromised. However, different Sars-CoV-2 vaccines may have various mechanisms of action and different associated potential risks. Please review local prescribing information of any specific Sars-CoV-2 vaccine and comply with local prescribing information requirements for specific contra-indications and special warnings and precautions for use.

Primary outcomes:
measure: Percentage of Participants With no Change or a Reduction From Baseline in the Number of Gadolinium Enhancing (GdE) Lesions at Month 12 Using Non-responder Imputation
timeFrame: Baseline (assessed at screening visit), Month 12
measure: Percentage of Participants With no Change or a Reduction From Baseline in the Number of Gadolinium Enhancing (GdE) Lesions at Month 12 Based on Observed Data
timeFrame: Baseline (assessed at screening visit), Month 12
Secondary outcomes:
measure: Number of Participants Who Continued Study Treatment From Baseline to Months 6 and 12
timeFrame: Baseline, Month 6, Month 12
measure: Change From Baseline in CD19+ B Cell Counts Obtained by FACS
timeFrame: Baseline, Month 6, Month 12
measure: Change From Baseline in CD20+ CD3+ T Cell Counts Obtained by FACS
timeFrame: Baseline, Month 6, Month 12
measure: Number of Participants With Suicidal Ideation or Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline (all prior history), Post-baseline (up to Month 12)
measure: Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Scores at Baseline, Month 6 and Month 12
timeFrame: Baseline, Month 6, Month 12
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug (Day 1) up to 30 days after last dose (Month 13)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Neurology Associates PC
state: Alabama
city: Phoenix
country: United States
facility: Ctr for Neurology and Spine
state: Arizona
city: Pomona
country: United States
facility: Neuro Center
state: California
city: Aurora
country: United States
facility: UC Health Neuroscience Ctr
state: Colorado
city: Hollywood
country: United States
facility: Infinity Clinical Research LLC
state: Florida
city: Tallahassee
country: United States
facility: AMO Corporation
state: Florida
city: Tampa
country: United States
facility: University Of South Florida
state: Florida
city: Lutherville
country: United States
facility: International Neurorehab Institute
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Cente
state: Massachusetts
city: Foxboro
country: United States
facility: Neurology Center of New England PC
state: Massachusetts
city: Wellesley
country: United States
facility: Dragonfly Research LLC
state: Massachusetts
city: Las Vegas
country: United States
facility: Cleveland Clinic Foundation
state: Nevada
city: Latham
country: United States
facility: Ms Ctr Of Northeastern Ny
state: New York
city: Westerville
country: United States
facility: Columbus Neuroscience
state: Ohio
city: Knoxville
country: United States
facility: Sibyl Wray MD Neurology PC
state: Tennessee
city: Dallas
country: United States
facility: Parkland Health and Hospital Systems
state: Texas
city: Round Rock
country: United States
facility: Central TX Neuro Consultants P A
state: Texas
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
city: Guaynabo
country: Puerto Rico
facility: Caribbean Center for Clinical Research, Inc
Study officials:
References: