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

Relapse Remitting Multiple Sclerosis Clinical Trial

— AGNOS  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05084638
• Other study ID #: COMB157GUS10
• Status: Recruiting
• Phase: Phase 4
• Start date: January 25, 2022
• Est. completion date: February 16, 2026

Study information

• Verified date: February 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 168
• Est. completion date: February 16, 2026
• Est. primary completion date: February 21, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapse Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Ofatumumab
20mg subcutaneous injection

Locations

Country	Name	City	State
Puerto Rico	Novartis Investigative Site	Guaynabo
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Alexandria	Louisiana
United States	Novartis Investigative Site	Altamonte Springs	Florida
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Boca Raton	Florida
United States	Novartis Investigative Site	Chandler	Arizona
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dayton	Ohio
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Gainesville	Florida
United States	Novartis Investigative Site	Hackensack	New Jersey
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Jefferson	Louisiana
United States	Novartis Investigative Site	Kirkland	Washington
United States	Novartis Investigative Site	Knoxville	Tennessee
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Maitland	Florida
United States	Novartis Investigative Site	Milwaukee	Wisconsin
United States	Novartis Investigative Site	Morgantown	West Virginia
United States	Novartis Investigative Site	New Orleans	Louisiana
United States	Novartis Investigative Site	North Massapequa	New York
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Pensacola	Florida
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Raleigh	North Carolina
United States	Novartis Investigative Site	Reno	Nevada
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Tacoma	Washington
United States	Novartis Investigative Site	Tallahassee	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Torrance	California
United States	Novartis Investigative Site	Washington	District of Columbia
United States	Novartis Investigative Site	West Hollywood	California
United States	Novartis Investigative Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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