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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04486716
Recruitment Status : Recruiting
First Posted : July 27, 2020
Last Update Posted : November 27, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Relapsing Multiple Sclerosis Drug: Ofatumumab Phase 3

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 every 4 weeks 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Open-label
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 19, 2020
Estimated Primary Completion Date : April 29, 2022
Estimated Study Completion Date : April 29, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Ofatumumab

Arm Intervention/treatment
Experimental: Ofatumumab
Investigational drug will be provided in an autoinjector for subcutaneous administration containing 20 mg ofatumumab (20 mg/0.4 ml) administered at baseline, Day 7, Day 14 and monthly thereafter
Drug: Ofatumumab
Investigational drug will be provided in an autoinjector for subcutaneous administration containing 20 mg ofatumumab (20 mg/0.4 ml)
Other Name: OMB157




Primary Outcome Measures :
  1. Number of participants with no change or reduction in gadolinium enhancing lesions at 12 months [ Time Frame: Baseline up to 12 months ]
    Magnetic Resonance Imaging (MRI) will be used to measure presence of new or reduction in number of gadolinium enhancing lesions. Each MRI scan will be previewed by a local neuroradiologist. The quality of each scan performed will be assessed by a central MRI reading center and evaluated for quality, completeness and adherence to the protocol.


Secondary Outcome Measures :
  1. Change from baseline for total CD19+ B cell counts and CD3+CD20+ T cell counts, [ Time Frame: Baseline up to 6 and 12 months ]
    Total CD19+ B cell counts cell counts, obtained by fluorescence activated cell sorting

  2. Change from baseline for CD3+CD20+ T cell counts, [ Time Frame: Baseline up to 6 and 12 months ]
    CD3+CD20+ T cell counts, obtained by fluorescence activated cell sorting

  3. Change from baseline for Treatment Satisfaction Questionnaire for Medication (TSQM-9) [ Time Frame: Baseline up to 6 and 12 months ]
    The Treatment Satisfaction Questionnaire for Medication (TSQM-9) will be used to evaluate the participants' satisfaction with Ofatumumab. The TSQM-9 is a psychometrically sound and valid participant reported outcome to measure participants' satisfaction with medication and a good predictor of adherence across different types of medication and participant population. The TSQM-9 is a 9 item questionnaire having a global satisfaction score ranging from 0-100. The questionnaire consists of 3 domains: satisfaction, convenience and effectiveness (3 items each). The domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain.

  4. Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline up to 6 and 12 months ]
    The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent).

  5. Number of participants with treatment emergent adverse events [ Time Frame: Baseline up 13 months (includes 30 day followup) or up to 21 months for patients entering extra safety follow-up ]
    Adverse event monitoring should be continued following the last dose of study treatment until B cells are repleted. Repletion is defined as a concentration > the participant's baseline value or > the lower limit of normal, whichever is observed first.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 55 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 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):

  1. 2 fully infused initial 300 mg ocrelizumab iv infusions
  2. From 1 to 4 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, 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)

  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. 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:

  1. 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.
  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
    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, 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.
  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. 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.
  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 (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).

  11. 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.
  12. Have received any live or live-attenuated vaccines (including for varicella-zoster virus or measles) within 2 months prior to first study drug administration.
  13. 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

  14. 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.
  15. 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.
  16. 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
  17. 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)
  18. Participants with severe hypoproteinaemia e.g. in nephrotic syndrome.
  19. 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.

  20. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04486716


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
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United States, Alabama
Novartis Investigative Site Recruiting
Birmingham, Alabama, United States, 35209
United States, Florida
Novartis Investigative Site Recruiting
Tallahassee, Florida, United States, 32308
United States, Ohio
Novartis Investigative Site Recruiting
Westerville, Ohio, United States, 43081
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04486716    
Other Study ID Numbers: COMB157GUS07
111,116 ( Other Identifier: FDA )
First Posted: July 27, 2020    Key Record Dates
Last Update Posted: November 27, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Ofatumumab
Relapsing multiple sclerosis
MS
RMS
CIS
RRMS
SPM
ocrelizumab
MRI
CD19 B
adult,
OMB157
open-label
rituximab
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Ofatumumab
Antineoplastic Agents