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

• ClinicalTrials.gov Identifier: NCT05084638
• Recruitment Status: Active, not recruiting
• First Posted: October 20, 2021
• Last Update Posted: May 10, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 182 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: February 16, 2026

Arms and Interventions

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

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

• 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

Locations

United States, Arizona

Novartis Investigative Site

Chandler, Arizona, United States, 85226

Novartis Investigative Site

Phoenix, Arizona, United States, 85013

Novartis Investigative Site

Phoenix, Arizona, United States, 85032

United States, California

Novartis Investigative Site

Los Angeles, California, United States, 90033

Novartis Investigative Site

Torrance, California, United States, 90509-2910

Novartis Investigative Site

West Hollywood, California, United States, 90048

United States, Colorado

Novartis Investigative Site

Aurora, Colorado, United States, 80045

United States, District of Columbia

Novartis Investigative Site

Washington, District of Columbia, United States, 20007

United States, Florida

Novartis Investigative Site

Altamonte Springs, Florida, United States, 32714

Novartis Investigative Site

Boca Raton, Florida, United States, 33486

Novartis Investigative Site

Gainesville, Florida, United States, 32610

Novartis Investigative Site

Maitland, Florida, United States, 32751

Novartis Investigative Site

Orlando, Florida, United States, 32806

Novartis Investigative Site

Pensacola, Florida, United States, 32514

Novartis Investigative Site

Tallahassee, Florida, United States, 32308

Novartis Investigative Site

Tampa, Florida, United States, 33612

United States, Georgia

Novartis Investigative Site

Atlanta, Georgia, United States, 30309

United States, Louisiana

Novartis Investigative Site

Jefferson, Louisiana, United States, 70121

United States, Massachusetts

Novartis Investigative Site

Worcester, Massachusetts, United States, 01655

United States, Michigan

Novartis Investigative Site

Detroit, Michigan, United States, 48202 2689

United States, Nevada

Novartis Investigative Site

Reno, Nevada, United States, 89521

United States, New Jersey

Novartis Investigative Site

Hackensack, New Jersey, United States, 07601

United States, New Mexico

Novartis Investigative Site

Albuquerque, New Mexico, United States, 87131-0001

United States, North Carolina

Novartis Investigative Site

Raleigh, North Carolina, United States, 27607

United States, Ohio

Novartis Investigative Site

Dayton, Ohio, United States, 45408

United States, Oklahoma

Novartis Investigative Site

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Novartis Investigative Site

Philadelphia, Pennsylvania, United States, 19107-5098

United States, Tennessee

Novartis Investigative Site

Knoxville, Tennessee, United States, 37922

United States, Texas

Novartis Investigative Site

Dallas, Texas, United States, 75390-9034

Novartis Investigative Site

Houston, Texas, United States, 77030

Novartis Investigative Site

San Antonio, Texas, United States, 78258

United States, Washington

Novartis Investigative Site

Kirkland, Washington, United States, 98034

Novartis Investigative Site

Tacoma, Washington, United States, 98405

United States, West Virginia

Novartis Investigative Site

Morgantown, West Virginia, United States, 26506

United States, Wisconsin

Novartis Investigative Site

Milwaukee, Wisconsin, United States, 53226

Puerto Rico

Novartis Investigative Site

Guaynabo, Puerto Rico, 00968

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05084638
• Other Study ID Numbers: COMB157GUS10
• First Posted: October 20, 2021
• Last Update Posted: May 10, 2024
• Last Verified: May 2024

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

• 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:

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