Clinical trial NCT05084638: Study to Assess the Effect of Ofatumumab in Treatment Naïve, Very Early RRMS Patients Benchmarked Against Healthy Controls.
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Relapse Remitting Multiple Sclerosis
Keywords: early relapsing multiple sclerosis
ofatumumab
healthy control
treatment naïve
young adult population
MS-related disability
biomarker
MRI
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-10-20
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Percentage of participants achieving NEDA-3 (No Evidence of Disease Activity-3)
timeFrame: Month 6 to month 18
Secondary outcomes:
measure: Number of relapses
timeFrame: Baseline to Month 18 and 30
measure: Number of participants that were 3-month Disability Worsening-free
timeFrame: Baseline up to Month 18 and 30
measure: Number of participants with NEDA (No Evidence of Disease Activity) - Clinical
timeFrame: Month 6 to Month 18
measure: Number of participants with NEDA (No Evidence of Disease Activity) - Radiological
timeFrame: Month 6 to Month 18
measure: Change from Baseline in Gd+ lesion count
timeFrame: Baseline to Month 18 and 30
measure: Change from Baseline in Gd+ lesion volume
timeFrame: Baseline to Month 18 and 30
measure: Change from Baseline in new/enlarging T2 lesion count
timeFrame: Baseline to Month 18 and 30
measure: Change from Baseline in T2 lesion volume
timeFrame: Baseline to Month 18 and 30
measure: Change from Baseline for NeuroQOL
timeFrame: Baseline to Month 18 and 30
measure: Change from Baseline for Patient Determined Disease Steps (PDDS)
timeFrame: Baseline to Month 18 and 30
measure: Brain volume loss (BVL) assessment (whole brain and regional)
timeFrame: Month 6 to Month 18 and 30
measure: Number of participants with treatment emergent adverse events
timeFrame: Baseline up to approximately Month 30
measure: Change from Baseline in new unenhancing T1 lesion number
timeFrame: Baseline to Month 18 and 30
measure: Change from Baseline in T1 unenhancing lesion volume
timeFrame: Baseline to Month 18 and 30
Other outcomes:
Locations:
city: Chandler
country: United States
facility: MD First Research
state: Arizona
city: Phoenix
country: United States
facility: Barrow Neurological Clinics at St Josephs Hospital and MC
state: Arizona
city: Phoenix
country: United States
facility: Arizona Neuroscience Research LLC
state: Arizona
city: Los Angeles
country: United States
facility: Keck School of Medicine
state: California
city: Torrance
country: United States
facility: Lundquist Inst BioMed at Harbor
state: California
city: West Hollywood
country: United States
facility: Regina Berkovich MD PhD Inc
state: California
city: Aurora
country: United States
facility: UC Health Neuroscience Ctr
state: Colorado
city: Washington
country: United States
facility: MedStar Health
state: District of Columbia
city: Altamonte Springs
country: United States
facility: Neurology of Central FL Res Ctr
state: Florida
city: Boca Raton
country: United States
facility: First Choice Neurology
state: Florida
city: Gainesville
country: United States
facility: Univ of Florida College of Medicine
state: Florida
city: Maitland
country: United States
facility: Neurology Associates PA
state: Florida
city: Orlando
country: United States
facility: Orlando Health Clinical Trials
state: Florida
city: Pensacola
country: United States
facility: Emerald Coast Neurology
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Neurological Clinic
state: Florida
city: Tampa
country: United States
facility: University Of South Florida
state: Florida
city: Atlanta
country: United States
facility: Shepherd Center
state: Georgia
city: New Orleans
country: United States
facility: Ochsner Cancer Institute
state: Louisiana
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Reno
country: United States
facility: Renown Institute for Neurosciences
state: Nevada
city: Hackensack
country: United States
facility: Neuroscience Institute at Hackensack
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Raleigh
country: United States
facility: Velocity Clinical Research
state: North Carolina
city: Dayton
country: United States
facility: Neurology Diagnostics Inc
state: Ohio
city: Oklahoma City
country: United States
facility: Multiple Sclerosis Center of Excellence of OMRF
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Knoxville
country: United States
facility: Sibyl Wray MD Neurology PC
state: Tennessee
city: Dallas
country: United States
facility: Univ of Texas Southwest Med Center
state: Texas
city: Houston
country: United States
facility: UT Health Science Center
state: Texas
city: San Antonio
country: United States
facility: Lonestar Neurology of San Antonio
state: Texas
city: Kirkland
country: United States
facility: Evergreen Health Multiple Sclerosis Center
state: Washington
city: Tacoma
country: United States
facility: MultiCare Neuroscience Center of Washington
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Guaynabo
country: Puerto Rico
facility: Caribbean Center for Clinical Research, Inc
Study officials:
References: