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

• ClinicalTrials.gov Identifier: NCT04486716
• Recruitment Status: Recruiting
• First Posted: July 27, 2020
• Last Update Posted: February 23, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: July 23, 2020
• First Posted Date: July 27, 2020
• Last Update Posted Date: February 23, 2023
• Actual Study Start Date: October 19, 2020
• Estimated Primary Completion Date: January 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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: Interventional
• Study Phase: Phase 3

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Open-label

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Relapsing Multiple Sclerosis

Intervention

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

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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 23, 2020): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 1, 2024
• Estimated Primary Completion Date: January 1, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

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

Contact: Novartis Pharmaceuticals

• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT04486716
• Other Study ID Numbers: 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

• 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: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: February 2023