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

Novartis Pharmaceuticals180 enrolled

Overview

This study evaluates 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 also assesses 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.

The study is an open-label, multi-center, prospective 18-month study in 119 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=61) for select outcomes to observe similarities and differences between the groups. After giving consent, participants have a 28-day screening/qualification period. If they qualify to continue, they start study measures including assessments of clinical and magnetic resonance imaging (MRI) metrics and use of a digital monitoring watch. Additionally, samples are collected for laboratory and biomarker analysis. RRMS participants begin treatment with ofatumumab for the next 18 months. Healthy participants undergo similar assessments; however they do not receive any treatment during the course of the study. Over the 18 months, participants have regular clinical visits with assessments and sample collection. After 18 months in the trial, participants in both groups 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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

Eligibility

Sex: ALLMin age: 18 YearsMax age: 35 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (36)

MD First Research

Chandler, Arizona, United States

Barrow Neurological Clinics at St Josephs Hospital and MC

Phoenix, Arizona, United States

Arizona Neuroscience Research LLC

Phoenix, Arizona, United States

Keck School of Medicine

Los Angeles, California, United States

Lundquist Inst BioMed at Harbor

Torrance, California, United States

Outcomes

Primary Outcomes

Percentage of Participants Achieving NEDA-3 (No Evidence of Disease Activity-3)

A participant is considered as achieved NEDA-3 if they were: * relapse-free, defined as no confirmed relapses in month 6 to 18. * 3-month clinical disability progression-free, defined as no clinical disability progression as measured by EDSS in month 6 to 18. * MRI activity-free, defined as no Gd+ lesions on any MRI scan after Month 6, or new/enlarging T2 lesions compared to Month 6 on any MRI scan after Month 6 Expanded Disability Status Scale (EDSS) ranges from 0 to 10 with higher values indicating increased disability. As per protocol and SAP only evaluated on the ofatumumab participants.

Time frame: Month 6 to month 18

Secondary Outcomes

Number of Confirmed MS Relapses in Months 6 to 18

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 , 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). Expanded Disability Status Scale (EDSS) ranges from 0 to 10 with higher values indicating increased disability. Confirmation of MS relapse was done centrally. As per protocol and SAP only evaluated on the ofatumumab participants.

Time frame: Month 6 to month 18

Participant Based Annualized Relapse Rate (ARR)

ARR (participant-based) is calculated at the participant level as \[(number of confirmed MS relapses in Months 6 to 18) / (number of days in Months 6 to 18)\] x 365.25. As per protocol and SAP only evaluated on the ofatumumab participants.

Time frame: Month 6 to month 18

Group Based Annualized Relapse Rate (ARR)

ARR (group-based) is calculated at the group level as \[(total number of confirmed MS relapses in Months 6 to 18 for all participants within the ofatumumab-treated cohort) / (total number of days in Months 6 to 18 for all participants within the ofatumumab-treated cohort)\] x 365.25. As per protocol and SAP only evaluated on the ofatumumab participants.

Time frame: Month 6 to month 18

Percentage of Participants That Were 3-month Disability Progression-free

3-month clinical disability progression-free was defined as no clinical disability progression as measured by EDSS (global assessment scale), where 3-month confirmed clinical disability progression was defined as an increase from Month 6 in EDSS sustained for at least 3 months. If a participant fulfilled the clinical disability progression criteria based on the single EDSS assessment at Month 18, it was considered a confirmed clinical disability progression (sustainment for at least 3 months was not required). If a participant died due to MS , it was considered a confirmed clinical disability progression regardless of the Month 6 EDSS or change in EDSS. Expanded Disability Status Scale (EDSS) ranges from 0 to 10 with higher values indicating increased disability. As per protocol and SAP only evaluated on the ofatumumab participants.

Time frame: Month 6 to month 18

Percentage 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 confirmed MS relapse in Months 6 to 18 and no 3-month confirmed clinical disability progression in Months 6 to 18 (based on change from Month 6 in EDSS). Expanded Disability Status Scale (EDSS) ranges from 0 to 10 with higher values indicating increased disability. As per protocol and SAP only evaluated on the ofatumumab participants.

Time frame: 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 had no Gd+ lesions on any MRI scan after Month 6, or new/enlarging T2 lesions compared to Month 6 on any MRI scan after Month 6 (MRI activity-free). Scheduled and unscheduled assessments are considered. As per protocol and SAP only evaluated on the ofatumumab participants.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: Baseline up to approximately Month 30

Change From Baseline in New Unenhancing T1 Lesion Number

Change in the number of new unenhancing T1 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.

Time frame: Baseline to Month 18 and 30

Change From Baseline in T1 Unenhancing Lesion Volume

Change in the size of T1 unenhancing 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.

Time frame: Baseline to Month 18 and 30

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

Overview

Conditions

Interventions

Eligibility

Locations (36)

Outcomes

Primary Outcomes

Secondary Outcomes