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Study to Assess the Effect of Ofatumumab in Treatment Naïve, Very Early RRMS Patients Benchmarked Against Healthy Controls. (AGNOS)

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ClinicalTrials.gov Identifier: NCT05084638
Recruitment Status : Recruiting
First Posted : October 20, 2021
Last Update Posted : January 17, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
This study will evaluate the impact of ofatumumab in Relapsing Remitting Multiple Sclerosis (RRMS) participants that are very early in the course of their disease using clinical and magnetic resonance imaging (MRI) outcomes. The study will also assess changes in disease using monitoring techniques including digital biometric device use, biomarker analysis and non-conventional MRI. Select outcomes in the ofatumumab treated group will be compared to a group of Healthy participants to determine if there are similarities between the groups after the patients with MS undergo treatment with ofatumumab.

Condition or disease Intervention/treatment Phase
Relapse Remitting Multiple Sclerosis Drug: Ofatumumab Phase 4

Detailed Description:

The study is an open-label, multi-center, prospective 18-month study in 118 MS participants with early RRMS (defined as within 6 months of diagnosis of clinically definite RRMS) and who are treatment naïve. It is designed to determine if RRMS participants treated with 20 mg subcutaneous monthly ofatumumab during the earliest part of their disease will benefit from the use of ofatumumab as their first disease modifying therapy. Additionally, RRMS patients will be compared to age- and sex-matched healthy participants (n=50) for select outcomes to observe similarities and differences between the groups.

After giving consent, participants will have a 28-day screening/qualification period. If they qualify to continue, they will start study measures including assessments of clinical and magnetic resonance imaging (MRI) metrics and use of a digital monitoring watch. Additionally, samples will be collected for laboratory and biomarker analysis. RRMS participants will begin treatment with ofatumumab for the next 18 months. Healthy participants will undergo similar assessments; however they will not receive any treatment during the course of the study. Over the 18 months, participants will have regular clinical visits with assessments and sample collection. After 18 months in the trial, participants in both groups will have the option to enter into a 12-month extension (up to 30 months total in study) to collect further information on long-term clinical and MRI outcomes.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 168 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: AGNOS: An 18-month, Open-label, Multi-Center Study to Assess the Effect of Ofatumumab 20mg SC Monthly in Treatment Naïve, Very Early Relapsing Remitting Multiple Sclerosis Patients Benchmarked Against Healthy Controls on Select Outcomes.
Actual Study Start Date : January 25, 2022
Estimated Primary Completion Date : February 21, 2025
Estimated Study Completion Date : June 22, 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Ofatumumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Ofatumumab
Ofatumumab will be provided in an autoinjector for subcutaneous administration. Dosing regimen for this study is an initial dose of 20mg at Baseline/Week 0, followed by Week 1, 2 and every month thereafter, beginning at Week 4 (Month 1) until Month 18. There will be an optional extension of dosing through month 30.
 Drug: Ofatumumab
20mg subcutaneous injection
Other Name: OMB157
No Intervention: Healthy Control
Healthy Control arm will be age- and sex-matched subjects (to the ofatumumab treated arm) and will not receive a study treatment.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of participants achieving NEDA-3 (No Evidence of Disease Activity-3) [ Time Frame: Month 6 to month 18 ]
    A participant is considered as achieved NEDA-3 if the participant has not had a clinical relapse (recurrence of a disease activity after a recovery), has not had an increase in disability and has no new radiological MRI activity (no new occurrences of contrast-enhancing lesions) during study Months 6 to 18.


Secondary Outcome Measures :
  1. Number of relapses [ Time Frame: Baseline to Month 18 and 30 ]
    Relapses are recurrences of a disease activity after a recovery. A confirmed MS relapse is one accompanied by a clinically relevant change in the EDSS performed by the EDSS Rater, i.e. an increase of at least 0.5 points on the EDSS score, or an increase of 1 point on two functional scores (FSs) or 2 points on one FS, excluding changes involving bowel/bladder or cerebral FS compared to the previous available rating (the last EDSS rating that did not occur during a relapse). Confirmation of MS relapse based on these definitions will be done centrally.

  2. Number of participants that were 3-month Disability Worsening-free [ Time Frame: Baseline up to Month 18 and 30 ]
    No increase or worsening of disability over a period of 3 months or more

  3. Number of participants with NEDA (No Evidence of Disease Activity) - Clinical [ Time Frame: Month 6 to Month 18 ]
    A participant is considered as achieved NEDA-Clinical if the participant has not had a clinical relapse (recurrence of a disease activity after a recovery).

  4. Number of participants with NEDA (No Evidence of Disease Activity) - Radiological [ Time Frame: Month 6 to Month 18 ]
    A participant is considered as achieved NEDA-radiological if the participant has has no new radiological MRI activity (no new occurrences of contrast-enhancing lesions) during study Months 6 to 18.

  5. Change from Baseline in Gd+ lesion count [ Time Frame: Baseline to Month 18 and 30 ]
    Change in the number of gadolinium enhancing lesions will be measured by Magnetic Resonance Imaging (MRI). 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.

  6. Change from Baseline in Gd+ lesion volume [ Time Frame: Baseline to Month 18 and 30 ]
    Change in size of gadolinium enhancing lesions will be measured by Magnetic Resonance Imaging (MRI). 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.

  7. Change from Baseline in new/enlarging T2 lesion count [ Time Frame: Baseline to Month 18 and 30 ]
    Change in the number of new/enlarging T2 lesions will be measured by Magnetic Resonance Imaging (MRI). 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.

  8. Change from Baseline in T2 lesion volume [ Time Frame: Baseline to Month 18 and 30 ]
    Change in size of T2 lesions will be measured by Magnetic Resonance Imaging (MRI). 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.

  9. Change from Baseline for NeuroQOL [ Time Frame: Baseline to Month 18 and 30 ]

    The NeuroQOL is a measurement system that evaluates and monitors the physical, mental, and social effects experienced by adults and children living with neurological conditions. The following domains will be measured.

    Physical Health, Mental Health, Social Health. Scales can be scored by summing the values of the response to each item to develop a total raw score.


  10. Change from Baseline for Patient Determined Disease Steps (PDDS) [ Time Frame: Baseline to Month 18 and 30 ]
    The PDDS is a standardized rating scale which is a self-assessment scale of functional disability in multiple sclerosis patients primarily based on ambulation. The questionnaire contains 1 question which is scored ranging from 0 (normal) to 8 (bedridden). A score of 0 to 2 indicates mild disability; a score of 3 to 5 indicates moderate disability; a score of 6 to 8 indicates severe disability.

  11. Brain volume loss (BVL) assessment (whole brain and regional) [ Time Frame: Month 6 to Month 18 and 30 ]
    Brain volume loss is a marker of progressive loss of brain structure and function. It is a predictor of disability progression. Evaluate the effect of ofatumumab vs healthy controls on 1) whole brain and regional atrophy measured at month 18/30 after re-baseline at 6 months; and 2) regional atrophy measured 18/30 months from Baseline

  12. Number of participants with treatment emergent adverse events [ Time Frame: Baseline up to approximately Month 30 ]
    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. Other safety assessments (physical exam, vital signs, etc) that meet the definition of an adverse event or are considered clinically relevant by the investigator will be reported as an adverse event.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Key Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

  1. Signed informed consent must be obtained prior to participation in the study

  2. Age 18-35 years

    Patients in the healthy control arm eligible for inclusion must fulfill the following criteria:

  3. Able to obtain MRI (HC with abnormal MRI at Screening will be excluded) and use wearable device

  4. Able to provide blood sample (no CSF will be collected in HC)

    Patients in the ofatumumab-treated arm eligible for inclusion must fulfill the following criteria:

  5. Diagnosis of RRMS per McDonald Criteria (2010/2017)
  6. Within 6 months of diagnosis of clinically definite MS (CDMS)
  7. EDSS 0-3.0 (Inclusive)
  8. Treatment-naïve to MS DMT
  9. Able to obtain MRI and attend study visits at sites
  10. Able to use wearable device
  11. Able to provide blood sample (and CSF for sub-group n=15)

Key Exclusion Criteria:

Participants in the healthy control arm meeting any of the following criteria are not eligible for inclusion in this study:

  1. Confounding medical condition as determined by the investigator

    RRMS patients fulfilling any of the following exclusion criteria are not eligible for inclusion in this study:

  2. Diseases other than multiple sclerosis responsible for the clinical or MRI presentation
  3. Patients with neuromyelitis optica, Radiologic/ Clinically Isolated Syndrome, Secondary Progressive or Primary Progressive MS diagnosis
  4. Use of experimental or investigational drugs for MS
  5. Previous use of Disease Modifying Therapy (DMT) or chemotherapeutic medications for MS
  6. Relapse between screening and Baseline visits
  7. Known sensitivity to gadolinium; patients with chronic, severe kidney disease
  8. Known history of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
  9. CNS anomalies that are better accounted for by another disease process or MRI anomalies causing clinically apparent impairments
  10. Known active malignancies
  11. Pregnant or nursing (lactating) women
  12. Females of childbearing potential (all women physiologically capable of becoming pregnant) should use effective contraception while receiving ofatumumab and for 6 months after the last treatment of ofatumumab
  13. Patients with an active chronic disease (or stable but treated with immune therapy) of the immune system other than MS or with immunodeficiency syndrome
  14. Patients with active infections including systemic bacterial, viral (including SARS-CoV-2/COVID-19) or fungal infections, or known to have AIDS or to test positive for HIV antibody at Screening
  15. Patients with neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML), or confirmed PML
  16. Patients with IgG or IgM levels below LLN at Screening
  17. Patients that have received any live or live-attenuated vaccines within 4 weeks prior to first dose of study drug administration
  18. Patients at risk of developing or having reactivation of hepatitis
Contacts and Locations
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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): NCT05084638


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, Arizona
Novartis Investigative Site Recruiting
Chandler, Arizona, United States, 85226
Novartis Investigative Site Recruiting
Phoenix, Arizona, United States, 85032
United States, Florida
Novartis Investigative Site Recruiting
Altamonte Springs, Florida, United States, 32714
Novartis Investigative Site Recruiting
Maitland, Florida, United States, 32751
Novartis Investigative Site Recruiting
Orlando, Florida, United States, 32806
Novartis Investigative Site Recruiting
Orlando, Florida, United States, 32825
Novartis Investigative Site Recruiting
Tallahassee, Florida, United States, 32308
United States, Louisiana
Novartis Investigative Site Recruiting
Alexandria, Louisiana, United States, 71301
United States, Michigan
Novartis Investigative Site Recruiting
Detroit, Michigan, United States, 48202
United States, New York
Novartis Investigative Site Recruiting
North Massapequa, New York, United States, 11758
United States, Ohio
Novartis Investigative Site Recruiting
Dayton, Ohio, United States, 45408
United States, Oklahoma
Novartis Investigative Site Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Novartis Investigative Site Recruiting
Knoxville, Tennessee, United States, 37922
United States, Texas
Novartis Investigative Site Recruiting
Dallas, Texas, United States, 75390-9034
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77030
Novartis Investigative Site Recruiting
San Antonio, Texas, United States, 78258
Puerto Rico
Novartis Investigative Site Recruiting
Guaynabo, Puerto Rico, 00968
Sponsors and Collaborators
Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05084638    
Other Study ID Numbers: COMB157GUS10
First Posted: October 20, 2021    Key Record Dates
Last Update Posted: January 17, 2023
Last Verified: January 2023
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

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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 ):
early relapsing multiple sclerosis
ofatumumab
healthy control
treatment naïve
 young adult population
MS-related disability
biomarker
MRI
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