Relapse Remitting Multiple Sclerosis
Conditions
Keywords
early relapsing multiple sclerosis, ofatumumab, healthy control, treatment naïve, young adult population, MS-related disability, biomarker, MRI
Brief summary
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.
Detailed description
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.
Interventions
DRUGOfatumumab
20mg subcutaneous injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving NEDA-3 (No Evidence of Disease Activity-3) | Month 6 to month 18 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Confirmed MS Relapses in Months 6 to 18 | Month 6 to month 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. |
| Participant Based Annualized Relapse Rate (ARR) | Month 6 to month 18 | 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. |
| Group Based Annualized Relapse Rate (ARR) | Month 6 to month 18 | 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. |
| Percentage of Participants That Were 3-month Disability Progression-free | Month 6 to month 18 | 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. |
| Percentage of Participants With NEDA (No Evidence of Disease Activity) - Clinical | Month 6 to month 18 | 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. |
| Number of Participants With NEDA (No Evidence of Disease Activity) - Radiological | Month 6 to month 18 | 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. |
| Change From Baseline in Gd+ Lesion Count | 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. |
| Change From Baseline in Gd+ Lesion Volume | 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. |
| Change From Baseline in New/Enlarging T2 Lesion Count | 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. |
| Change From Baseline in T2 Lesion Volume | 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. |
| Change From Baseline for NeuroQOL | 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. |
| Change From Baseline for Patient Determined Disease Steps (PDDS) | 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. |
| Brain Volume Loss (BVL) Assessment (Whole Brain and Regional) | 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 |
| Number of Participants With Treatment Emergent Adverse Events | 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. |
| Change From Baseline in New Unenhancing T1 Lesion Number | Baseline to Month 18 and 30 | 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. |
| Change From Baseline in T1 Unenhancing Lesion Volume | Baseline to Month 18 and 30 | 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. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled in 36 sites in the United States
Pre-assignment details
The trial consists of a 4 week screening period before first treatment (day 1), an 18 month open-label treatment phase , an optional 12 month open-label extension and a 100 day safety follow-up. The Open-Label extension and safety follow up were still ongoing at the date of data cut-off.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 27.9 years STANDARD_DEVIATION 4.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Sex/Gender, Customized Female | 89 Participants |
| Sex/Gender, Customized Male | 24 Participants |
| Sex/Gender, Customized Undifferentiated | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 119 | 0 / 61 |
| other Total, other adverse events | 99 / 119 | 27 / 61 |
| serious Total, serious adverse events | 8 / 119 | 3 / 61 |
Outcome results
None listed