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NCT Number: NCT03650114

Long-term Safety, Tolerability and Effectiveness Study of Ofatumumab in Patients With Relapsing MS

The purpose of this study is to collect long-term safety, tolerability, effectiveness and health outcomes data in eligible subjects who have participated in a Novartis ofatumumab clinical MS study.

Vaccination sub-study The purpose of this research sub-study is to find out the effects of ofatumumab on the development of antibody responses to selected vaccines and keyhole limpet hemocyanin (KLH) neo-antigen in subjects with relapsing multiple sclerosis (RMS).

COVID-19 sub-study:

The purpose of this research sub-study is to explore the immune response following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination in a subset of subjects on long-term ofatumumab 20 mg sc. Note: Novartis is not supplying the SARS-CoV-2 vaccine.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Relapsing Multiple Sclerosis

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Novartis Investigative Site, Rosario, Santa Fe Province, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Must have completed a selected Novartis MS study which dosed ofatumumab 20 mg sc every 4 weeks
  • Written informed consent

Exclusion criteria

  • Emergence of any clinically significant condition/disease during the previous ofatumumab study in which study participation might result in safety risk for the subject
  • Subjects with active systemic bacterial, viral or fingal infections, or chronic infection (e.g. AIDS)
  • Subjects taking medications prohibited by the protocol
  • Pregnant or nursing (lactating) women Other protocol-defined inclusion/exclusion criteria may apply

Vaccination sub-study:

Inclusion criteria

  • Informed consent
  • Actively enrolled in the COMB157G2399 Study
  • 12 weeks of continuous treatment within the COMB157G2399 Study
  • prior vaccination history as per protocol-defined

Exclusion criteria

  • known hypersensitivity or history of systemic allergic, neurologic or other reactions to vaccines
  • allergies to egg or shellfish
  • any safety findings including low IgG/IgM requiring ofatumumab interruption within 12 weeks prior to vaccination sub-study start
  • any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 2 weeks of the first vaccination sub-study visit

Other protocol-defined inclusion/exclusion criteria may apply

Treatment and study plan

Ofatumumab

Biological

subcutaneous injection of 20 mg ofatumumab every 4 weeks

Tetanus toxoid (TT) containing vaccine (Td, Tdap)

Biological

0.5mL Vial/Syringe Containing 5 limit of flocculation (LF) tetanus toxoid

13-valent pneumococcal conjugate vaccine (13-PCV)

Biological

0.5mL Vial/Syringe

23-valent pneumococcal polysaccharide vaccine (23-PPV)

Biological

0.5mL Vial/Syringe

Seasonal Quadrivalent influenza vaccine

Biological

Seasonal 2020-2021 0.5mL Vial/Syringe (trivalent may be used where quadrivalent is not available)

Keyhole limpet hemocyanin (KLH) neo-antigen

Biological

1mg Vial

Primary outcomes

  1. Number of patients that experience an adverse event or abnormal laboratory, vital and/or ECG results and positive suicidiality outcomes

    Time frame: Up to 8 years

Secondary outcomes

  1. Number of relapse rates per year

    Time frame: Data from the core studies through the first 5 years in this study.

    Annual Relapse Rate (ARR) time calculated as number of confirmed relapses divided by time in study per year and will also be presented for the entire duration

  2. Patients with confirmed 3 and 6 month disability worsening

    Time frame: During the first 5 years of treatment in the study.

    A confirmed disability worsening is an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at last 3, or 6 months EDSS consists of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, and Cerebral functions (Fatigue contributes).

  3. Patients with confirmed 6, 12, and 24 month disability improvement and improvement during the first 5 years of the study.

    Time frame: During the first 5 years of treatment in the study.

    Confirmed disability improvement is a decrease from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6, 12 or 24 months EDSS consists of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, and Cerebral functions (Fatigue contributes).

  4. Patients with changes in Expanded Disability Status Scale (EDSS) scores

    Time frame: Data from the core studies through the first 5 years in this study, (depending on if first dose was in the core or in this extension study or comparator randomization)

    Score changes in Expanded Disability Status Scale (EDSS) over time EDSS consists of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, and Cerebral functions (Fatigue contributes).

  5. Changes in and time to 6 month confirmed worsening of Symbol Digit Modalities Test Scores

    Time frame: During the first 5 years of the study.

    Score changes and confirmed 4-point worsening sustained for 6 months in Symbol Digit Modalities Test (SDMT) scores The Symbol Digit Modalities Test is a neuropsychological, timed test for sustained attention and concentration. 3 versions will be used, alternating at each visit where done. The number of correct responses will be counted for the score.

  6. Changes in the Magnetic Resonance Image (MRI) related to brain volume loss

    Time frame: Data from the core studies through the first 5 years in this study.

    Percent change from baseline in brain volume loss (BVL)

  7. Changes in the Magnetic Resonance Image (MRI) related to T2 lesions

    Time frame: Data from the core studies through the first 5 years in this study.

    Number of new or enlarging T2 lesions

  8. Changes in the Magnetic Resonance Image (MRI) related to Gd-enhancing lesions

    Time frame: Data from the core studies through the first 5 years in this study.

    Total number of Gd-enhancing lesions on all MRI scans adjusted for different time of scan versus follow up time in study

  9. Changes in neurofilament light change serum concentration

    Time frame: Data from the core studies through the first 5 years in this study.

    Extent of neurofilament light change concentration in blood NfL is a component of the neuronal cytoskeleton and is released into the cerebrospinal fluid and into subsequently blood following neuro-axonal damage

Other outcomes

  1. Hummoral immune response to TT vaccine

    Time frame: Pre-vaccination, 4 and 8 weeks post-vaccination

    Proportion of subjects with a positive antibody response to TT vaccine measured 4 and 8 weeks after vaccination while treated with ofatumumab

    • 2-fold increase in titer level
    • Tetanus anti-bodies ≥ 0.2 IU/mL
    • Mean titers of anti-tetanus antibody

  2. Hummoral immune response to 13-valent pneumococcal conjugate vaccine (13-PCV)

    Time frame: 4 and 8 weeks

    Proportion of subjects with a positive antibody response against individual anti-pneumococcal antibody serotypes while treated with ofatumumab

    • 2-fold increase in titer level or a > 1 microgram/mL rise in titer compared with pre-immunization titer
    • Positive anti-body response against at least 2 of the 13 pneumococcal antibody serotypes
    • Positive anti-body response against at least 50% of serotypes
    • Mean titers of anti-pneumococcal antibody

  3. Hummoral immune response to 13-PCV boosted eight weeks later by 23-valent pneumococcal polysaccharide vaccine (23-PPV)

    Time frame: Pre-vaccination, 4 and 8 weeks post-vaccination

    Proportion of subjects with a positive antibody response against individual anti-pneumococcal antibody serotypes (23 serotypes to be tested individually) measured 4 and 8 weeks after the booster 23-PPV while the subject continues to be treated with ofatumumab

    • 2-fold increase in titer level or a > 1 microgram/mL rise in titer compared with pre-immunization titer
    • Positive anti-body response against at least 2 of the 23 pneumococcal antibody serotypes
    • Positive anti-body response against at least 50% of serotypes
    • Mean titers of anti-pneumococcal antibody

  4. Humoral immune response to KLH neo-antigen

    Time frame: Pre-administration, 4, 8, 12 weeks after initial administration and 4 weeks after last administration

    Mean titers of anti-KLH antibody measured immediately prior the first administration of KLH and measured immediately prior to the first administration, 4, 8 and 12 weeks after the first administration, and measured 4 weeks post last administration of KLH

  5. Hummoral immune response to 2020-2021 seasonal quadrivalent influenza vaccine

    Time frame: Pre-vaccination and 4 weeks post-vaccination

    Proportion of subjects fulfilling:

    • Seroconversion: The pre-vaccination HI antibody titer is < 1:10 and the postvaccination measurement is ≥ 1:40 (this applies to subjects with a pre-vaccination HI titer < 1:10), or
    • Significant increase in HI antibody titer: The pre-vaccination HI antibody titer is ≥ 1:10 and the increase from the pre- to the post-vaccination measurement is ≥ 4-fold (this applies to subjects with a pre-vaccination HI titer ≥ 1:10)

  6. Antibody response rate to TT and influenza vaccination as a function of exposure to ofatumumab

    Time frame: 8 weeks

    Immune response to TT and influenza vaccination

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

An Open-label, Single Arm, Multi-center Extension Study Evaluating Long-term Safety, Tolerability and Effectiveness of Ofatumumab in Subjects With Relapsing Multiple Sclerosis

Acronym: ALITHIOS

Important dates

Study start
2018
Primary completion
2028
Study completion
2028
First posted
Aug 28, 2018
Registry last updated
May 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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