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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 : January 19, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE July 23, 2020
First Posted Date  ICMJE July 27, 2020
Last Update Posted Date January 19, 2023
Actual Study Start Date  ICMJE October 19, 2020
Estimated Primary Completion Date January 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 23, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2020)
  • 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
  • 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
  • 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.
  • 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).
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Single Arm Study Evaluating the Efficacy, Safety and Tolerability of Ofatumumab in Patients With Relapsing Multiple Sclerosis
Official Title  ICMJE 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)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Open-label
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsing Multiple Sclerosis
Intervention  ICMJE 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
Study Arms  ICMJE 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
Intervention: Drug: Ofatumumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 23, 2020)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2024
Estimated Primary Completion Date January 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04486716
Other Study ID Numbers  ICMJE COMB157GUS07
111,116 ( Other Identifier: FDA )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Current Responsible Party Novartis ( Novartis Pharmaceuticals )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novartis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP