Efficacy and Safety of Ofatumumab and Siponimod Compared to Fingolimod in Pediatric Patients With Multiple Sclerosis (NEOS)

April 20, 2024 updated by: Novartis Pharmaceuticals

A 2-year Randomized, 3-arm, Double-blind, Non-inferiority Study Comparing the Efficacy and Safety of Ofatumumab and Siponimod Versus Fingolimod in Pediatric Patients With Multiple Sclerosis Followed by an Open-label Extension

Efficacy and safety of ofatumumab and siponimod compared to fingolimod in pediatric patients with multiple sclerosis

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study is divided into a Core Part and Extension Part. The Core Part is a 24-month, double-blind, triple dummy, randomized, 3-arm active-controlled in children/adolescent patients aged 10-17 years old with Multiple Sclerosis (MS). The Extension Part is 60-month (5 year) open label (except for first 12 weeks transition which will remain double-blind) treatment for patients who complete the Core Part of the study and meet all inclusion/exclusion criteria. The targeted enrollment is 180 participants with multiple sclerosis which will include at least 5 participants with body weight (BW) ≤40 kg and at least 5 participants with age 10 to 12 years in each of the ofatumumab and siponimod arms. There is a minimum 6 month follow up period for all participants (core and extension). Total duration of the study could be up to 7 years.

Study Type

Interventional

Enrollment (Estimated)

180

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

Study Locations

  • Argentina
    • Buenos Aires
      • Caba, Buenos Aires, Argentina, C1181ACH
        • Recruiting
        • Novartis Investigative Site
  • Australia
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Recruiting
        • Novartis Investigative Site
  • Austria
      • Vienna, Austria, 1090
        • Recruiting
        • Novartis Investigative Site
  • Belgium
      • Esneux, Belgium, 4130
        • Recruiting
        • Novartis Investigative Site
      • Gent, Belgium, 9000
        • Recruiting
        • Novartis Investigative Site
  • Brazil
    • PR
      • Curitiba, PR, Brazil, 81210-310
        • Recruiting
        • Novartis Investigative Site
    • RS
      • Porto Alegre, RS, Brazil, 90430-001
        • Recruiting
        • Novartis Investigative Site
    • SP
      • Sao Paulo, SP, Brazil, 05403-000
        • Recruiting
        • Novartis Investigative Site
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Recruiting
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Recruiting
        • Novartis Investigative Site
      • Montreal, Quebec, Canada, H3A 2B4
        • Recruiting
        • Novartis Investigative Site
  • Chile
    • Santiago
      • Lo Barnechea, Santiago, Chile, 7691236
        • Recruiting
        • Novartis Investigative Site
  • Croatia
      • Zagreb, Croatia, 10000
        • Recruiting
        • Novartis Investigative Site
  • Estonia
      • Tallinn, Estonia, 11315
        • Recruiting
        • Novartis Investigative Site
  • France
      • Le Kremlin Bicetre, France, 94275
        • Recruiting
        • Novartis Investigative Site
      • Montpellier, France, 34295
        • Recruiting
        • Novartis Investigative Site
      • Strasbourg, France, 67098
        • Recruiting
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 13353
        • Recruiting
        • Novartis Investigative Site
      • Bochum, Germany, 44791
        • Recruiting
        • Novartis Investigative Site
      • Erlangen, Germany, 91054
        • Recruiting
        • Novartis Investigative Site
      • Freiburg, Germany, 79106
        • Recruiting
        • Novartis Investigative Site
      • Gottingen, Germany, 37075
        • Recruiting
        • Novartis Investigative Site
  • Guatemala
      • Guatemala, Guatemala, 01015
        • Recruiting
        • Novartis Investigative Site
  • India
    • Delhi
      • New Delhi, Delhi, India, 110017
        • Recruiting
        • Novartis Investigative Site
      • New Delhi, Delhi, India, 110 060
        • Withdrawn
        • Novartis Investigative Site
    • Kerala
      • Kochi, Kerala, India, 682041
        • Recruiting
        • Novartis Investigative Site
    • Uttar Pradesh
      • Lucknow, Uttar Pradesh, India, 226014
        • Recruiting
        • Novartis Investigative Site
    • West Bengal
      • Kolkata, West Bengal, India, 700017
        • Recruiting
        • Novartis Investigative Site
  • Israel
      • Petach-Tikva, Israel, 49202
        • Recruiting
        • Novartis Investigative Site
  • Italy
      • Napoli, Italy, 80131
        • Recruiting
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20132
        • Recruiting
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00165
        • Recruiting
        • Novartis Investigative Site
  • Latvia
      • Riga, Latvia, LV-1004
        • Recruiting
        • Novartis Investigative Site
  • Mexico
      • Chihuahua, Mexico, 31203
        • Recruiting
        • Novartis Investigative Site
    • Distrito Federal
      • Ciudad de Mexico, Distrito Federal, Mexico, 06700
        • Recruiting
        • Novartis Investigative Site
      • Mexico, Distrito Federal, Mexico, 06720
        • Recruiting
        • Novartis Investigative Site
  • Poland
      • Gdansk, Poland, 80 952
        • Recruiting
        • Novartis Investigative Site
      • Lodz, Poland, 93-338
        • Recruiting
        • Novartis Investigative Site
      • Poznan, Poland, 60-355
        • Recruiting
        • Novartis Investigative Site
      • Warsaw, Poland, 04 730
        • Recruiting
        • Novartis Investigative Site
  • Portugal
      • Coimbra, Portugal, 3000-602
        • Recruiting
        • Novartis Investigative Site
      • Lisboa, Portugal, 1169-050
        • Recruiting
        • Novartis Investigative Site
  • Romania
      • Bucuresti, Romania, 041914
        • Recruiting
        • Novartis Investigative Site
  • Russian Federation
      • St Petersburg, Russian Federation, 190000
        • Recruiting
        • Novartis Investigative Site
  • Serbia
      • Belgrade, Serbia, 11000
        • Recruiting
        • Novartis Investigative Site
  • Slovakia
      • Bratislava, Slovakia, 833 40
        • Recruiting
        • Novartis Investigative Site
  • Spain
    • Andalucia
      • Sevilla, Andalucia, Spain, 41009
        • Recruiting
        • Novartis Investigative Site
    • Asturias
      • Oviedo, Asturias, Spain, 33011
        • Recruiting
        • Novartis Investigative Site
    • Vizcaya
      • Baracaldo, Vizcaya, Spain, 48903
        • Recruiting
        • Novartis Investigative Site
  • Taiwan
      • Kaohsiung, Taiwan, 83301
        • Recruiting
        • Novartis Investigative Site
      • Tainan, Taiwan, 70403
        • Recruiting
        • Novartis Investigative Site
      • Taipei, Taiwan, 10002
        • Recruiting
        • Novartis Investigative Site
  • Turkey
      • Izmir, Turkey, 35340
        • Completed
        • Novartis Investigative Site
      • Izmir, Turkey, 35575
        • Recruiting
        • Novartis Investigative Site
      • Kocaeli, Turkey, 41380
        • Recruiting
        • Novartis Investigative Site
      • Samsun, Turkey, 55139
        • Recruiting
        • Novartis Investigative Site
    • TUR
      • Istanbul, TUR, Turkey, 34098
        • Recruiting
        • Novartis Investigative Site
  • United Kingdom
      • London, United Kingdom, WC1N 1EH
        • Recruiting
        • Novartis Investigative Site
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Recruiting
        • Arkansas Childrens Hosp Rsch Inst .
        • Contact:
        • Principal Investigator:
          • Virginia Erin Willis
    • California
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Childrens Hospital Los Angeles .
        • Contact:
        • Principal Investigator:
          • Jonathan Santoro
      • San Diego, California, United States, 92103
        • Recruiting
        • University of California San Diego
        • Principal Investigator:
          • Jennifer Graves
        • Contact:
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Recruiting
        • Children's National Medical Center .
        • Contact:
        • Principal Investigator:
          • Alexandra Kornbluh
    • Florida
      • Tampa, Florida, United States, 33609
        • Recruiting
        • Axiom Clinical Research of Florida
        • Principal Investigator:
          • Mark Cascione
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Recruiting
        • Childrens Healthcare of Atlanta .
        • Contact:
        • Principal Investigator:
          • Grace Gombolay
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Uni of Louisville Clncl Trials Unit Novak Center
        • Principal Investigator:
          • Michael Sweeney
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic - Rochester
        • Contact:
        • Principal Investigator:
          • Jan-Mendelt Tillema
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington Uni School of Med Main Center
        • Contact:
        • Principal Investigator:
          • Soe Mar
    • Oregon
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence St Vincent Med Center .
        • Principal Investigator:
          • Alison Christy
        • Contact:
          • Phone Number: 503-216-1234
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104 4399
        • Recruiting
        • Childrens Hospital of Philadelphia .
        • Contact:
        • Principal Investigator:
          • Amy Waldman
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern Main Center
        • Contact:
        • Principal Investigator:
          • Cynthia Wang
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Withdrawn
        • The University of Utah Health Image and Neurosciences
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Withdrawn
        • West Virginia University Cardio
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin .
        • Contact:
        • Principal Investigator:
          • Ahmed Obeidat

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 17 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Between 10 to <18 years of age (i.e., have not yet had their 18th birthday) at randomization
  2. Diagnosis of multiple sclerosis
  3. EDSS score of 0 to 5.5, inclusive
  4. At least one MS relapse/attack during the previous year or two MS relapses in the previous two years prior or evidence of one or more new T2 lesions within 12 months

Exclusion Criteria:

  1. Participants with progressive MS
  2. Participants with an active, chronic disease of the immune system other than MS
  3. Participants meeting the definition of ADEM
  4. Participants with severe cardiac disease or significant findings on the screening ECG.
  5. Participants with severe renal insufficiency

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ofatumumab - 20 mg injection/ placebo
Ofatumumab as a solution for injection in an autoinjector containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content) for subcutaneous administration. A loading dose at Day1, Day 7 and Day 14 and then injections every 4 weeks/ 6 weeks (depending on patient's body weight).
Drug: Ofatumumab
Ofatumumab as a solution for injection in an autoinjector containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content) for subcutaneous administration. A loading dose at Day1, Day 7 and Day 14 and then injections every 4 weeks/ 6 weeks (depending on patient's body weight).
Other Names:
  • OMB157
Other: Ofatumumab placebo
Ofatumumab matching placebo autoinjector
Experimental: siponimod - 0.5 mg, 1 mg or 2 mg/ placebo
Siponimod tablet administered orally once daily. Titration period, Day 1 to Day 6, first dose is either 0.1 mg or 0.25 mg up to daily dose of either 0.5 mg, 1 mg or 2 mg (depending on CYP2C9 genotype and body weight).
Drug: Siponimod
Siponimod tablet administered orally once daily. Titration period, Day 1 to Day 6, first dose is either 0.1 mg or 0.25 mg up to daily dose of either 0.5 mg, 1 mg or 2 mg (depending on CYP2C9 genotype and body weight).
Other Names:
  • BAF312
Other: Siponimod placebo
Siponimod matching placebo tablet
Active Comparator: fingolimod - 0.5 mg or 0.25 mg/ placebo
Fingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight).
Drug: Fingolimod
Fingolimod capsule administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight).
Other Names:
  • FTY720
Other: Fingolimod placebo
Fingolimod matching placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualized relapse rate (ARR) in target pediatric participants
Time Frame: Baseline up to 24 months
Frequency of relapses assessed by the annualized relapse rate (ARR). The ARR is defined as the average number of confirmed relapses per year (total number of confirmed relapses divided by the total days in the study multiplied by 365.25).
Baseline up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualized relapse rate (ARR) as compared to historical interferon β-1a data
Time Frame: Baseline up to 24 months
Frequency of relapses assessed by the annualized relapse rate (ARR) to historical interferon β-1a data. The ARR is defined as the average number of confirmed relapses per year. The historical data for interferon β-1a will derived from prior phase 3 studies.
Baseline up to 24 months
Annualized T2 lesion rate
Time Frame: Baseline up to 24 months
Number of new/newly enlarged T2 lesions per year
Baseline up to 24 months
Neurofilament light chain (NfL) concentrations
Time Frame: Day 1, Months 3,6,12,18,24
Neurofilament light chain (NfL) concentration in serum of ofatumumab and/or siponimod versus fingolimod
Day 1, Months 3,6,12,18,24
Plasma Concentrations of ofatumumab
Time Frame: Day 1, pre-dose for Day 7, Months 2,3,5,6,12,18,24
Ofatumumab plasma concentrations
Day 1, pre-dose for Day 7, Months 2,3,5,6,12,18,24
Plasma Concentrations of siponimod
Time Frame: Day 1 (2,3,4,6 h), Day 3 (2,3,4,6 h), pre-dose for Months 1 (pre, 3h), 3,5,12
Siponimod plasma concentrations
Day 1 (2,3,4,6 h), Day 3 (2,3,4,6 h), pre-dose for Months 1 (pre, 3h), 3,5,12
Plasma Concentrations of siponimod metabolite (M17)
Time Frame: Pre-dose Month 3, 5 and Month 12
Siponimod metabolite (M17) plasma concentration
Pre-dose Month 3, 5 and Month 12
Percentage of participants with anti-ofatumumab antibodies
Time Frame: Day 1, Pre-Dose Months 2,3,5,6,12,18,24
Anti-ofatumumab antibodies to demonstrate immunogenicity of ofatumumab
Day 1, Pre-Dose Months 2,3,5,6,12,18,24
Number of adverse events and serious adverse events
Time Frame: Baseline up approximately 66 months
Any clinically relevant finding that meets the criteria of an adverse event (as determined by the investigator) identified during the safety assessments (ECG, laboratory and ophthalmological data, pulmonary function tests and vital signs) will be reported as an adverse event
Baseline up approximately 66 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 5, 2021

Primary Completion (Estimated)

March 2, 2027

Study Completion (Estimated)

December 23, 2031

Study Registration Dates

First Submitted

June 14, 2021

First Submitted That Met QC Criteria

June 14, 2021

First Posted (Actual)

June 15, 2021

Study Record Updates

Last Update Posted (Actual)

April 23, 2024

Last Update Submitted That Met QC Criteria

April 20, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CBAF312D2301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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