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

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Relapse Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: Ofatumumab

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 Type: Interventional
• Enrollment (Estimated): 168
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• Puerto Rico
  • Guaynabo, Puerto Rico, 00968
    • Active, not recruiting
    • Novartis Investigative Site
• United States
  • Arizona
    • Chandler, Arizona, United States, 85226
      • Active, not recruiting
      • Novartis Investigative Site
    • Phoenix, Arizona, United States, 85013
      • Active, not recruiting
      • Novartis Investigative Site
    • Phoenix, Arizona, United States, 85032
      • Active, not recruiting
      • Novartis Investigative Site
  • California
    • Los Angeles, California, United States, 90033
      • Active, not recruiting
      • Novartis Investigative Site
    • Torrance, California, United States, 90509-2910
      • Active, not recruiting
      • Novartis Investigative Site
    • West Hollywood, California, United States, 90048
      • Active, not recruiting
      • Novartis Investigative Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Active, not recruiting
      • Novartis Investigative Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Active, not recruiting
      • Novartis Investigative Site
  • Florida
    • Altamonte Springs, Florida, United States, 32714
      • Active, not recruiting
      • Novartis Investigative Site
    • Boca Raton, Florida, United States, 33486
      • Active, not recruiting
      • Novartis Investigative Site
    • Gainesville, Florida, United States, 32610
      • Active, not recruiting
      • Novartis Investigative Site
    • Maitland, Florida, United States, 32751
      • Active, not recruiting
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32806
      • Active, not recruiting
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32825
      • Withdrawn
      • Novartis Investigative Site
    • Pensacola, Florida, United States, 32514
      • Active, not recruiting
      • Novartis Investigative Site
    • Tallahassee, Florida, United States, 32308
      • Active, not recruiting
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33612
      • Active, not recruiting
      • Novartis Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Active, not recruiting
      • Novartis Investigative Site
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Withdrawn
      • Novartis Investigative Site
    • Jefferson, Louisiana, United States, 70121
      • Active, not recruiting
      • Novartis Investigative Site
    • New Orleans, Louisiana, United States, 70115
      • Recruiting
      • Novartis Investigative Site
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • Active, not recruiting
      • Novartis Investigative Site
  • Michigan
    • Detroit, Michigan, United States, 48202 2689
      • Active, not recruiting
      • Novartis Investigative Site
  • Nevada
    • Reno, Nevada, United States, 89521
      • Active, not recruiting
      • Novartis Investigative Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Active, not recruiting
      • Novartis Investigative Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-0001
      • Active, not recruiting
      • Novartis Investigative Site
  • New York
    • North Massapequa, New York, United States, 11758
      • Withdrawn
      • Novartis Investigative Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Active, not recruiting
      • Novartis Investigative Site
  • Ohio
    • Dayton, Ohio, United States, 45408
      • Active, not recruiting
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Active, not recruiting
      • Novartis Investigative Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107-5098
      • Active, not recruiting
      • Novartis Investigative Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Active, not recruiting
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75390-9034
      • Active, not recruiting
      • Novartis Investigative Site
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78258
      • Active, not recruiting
      • Novartis Investigative Site
  • Washington
    • Kirkland, Washington, United States, 98034
      • Active, not recruiting
      • Novartis Investigative Site
    • Tacoma, Washington, United States, 98405
      • Active, not recruiting
      • Novartis Investigative Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Active, not recruiting
      • Novartis Investigative Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Active, not recruiting
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants achieving NEDA-3 (No Evidence of Disease Activity-3)	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.	Month 6 to month 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of relapses	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.	Baseline to Month 18 and 30
Number of participants that were 3-month Disability Worsening-free	No increase or worsening of disability over a period of 3 months or more	Baseline up to Month 18 and 30
Number of participants with NEDA (No Evidence of Disease Activity) - Clinical	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).	Month 6 to Month 18
Number of participants with NEDA (No Evidence of Disease Activity) - Radiological	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.	Month 6 to Month 18
Change from Baseline in Gd+ lesion count	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.	Baseline to Month 18 and 30
Change from Baseline in Gd+ lesion volume	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.	Baseline to Month 18 and 30
Change from Baseline in new/enlarging T2 lesion count	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.	Baseline to Month 18 and 30
Change from Baseline in T2 lesion volume	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.	Baseline to Month 18 and 30
Change from Baseline for NeuroQOL	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.	Baseline to Month 18 and 30
Change from Baseline for Patient Determined Disease Steps (PDDS)	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.	Baseline to Month 18 and 30
Brain volume loss (BVL) assessment (whole brain and regional)	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	Month 6 to Month 18 and 30
Number of participants with treatment emergent adverse events	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.	Baseline up to approximately Month 30

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2022
• Primary Completion (Estimated): February 21, 2025
• Study Completion (Estimated): February 16, 2026

Study Registration Dates

• First Submitted: October 7, 2021
• First Submitted That Met QC Criteria: October 7, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: MRI; biomarker; ofatumumab; healthy control; treatment naïve; early relapsing multiple sclerosis; young adult population; MS-related disability
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Antineoplastic Agents; Ofatumumab
• Other Study ID Numbers: COMB157GUS10

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.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No