Non-inferiority Study of Ocrelizumab and Rituximab in Active Multiple Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 27 May 2024
• Main ID: NCT04688788
• Date of registration: 22/12/2020
• Prospective Registration: Yes
• Primary sponsor: Rigshospitalet, Denmark
• Public title: Non-inferiority Study of Ocrelizumab and Rituximab in Active Multiple Sclerosis DanNORMS
• Scientific title: Danish Non-inferiority Study of Ocrelizumab and Rituximab in MS (DanNORMS): A Randomized Study Comparing the Efficacy of Ocrelizumab and Rituximab in Active Multiple Sclerosis
• Date of first enrolment: April 28, 2021
• Target sample size: 600
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04688788
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Denmark

Contacts

• Name: Jeppe Romme Christensen, MD, PhD
• Affiliation: Danish Multiple Sclerosis Center Rigshospitalet

Key inclusion & exclusion criteria

Inclusion Criteria:

- MS diagnosis and definition of disease course according to the 2017 McDonald criteria

- Expanded disability status scale (EDSS) =6.5

- Fulfilling criteria for active MS:

- Treatment naïve relapsing remitting multiple sclerosis (RRMS) patients (never
treated, or no DMT the previous 2 years):

1. ?=2 relapse previous 12 months OR

2. 1 relapse previous 12 months with severe residual symptoms and EDSS = 3.0 OR

3. 1 relapse previous 12 months AND =9 T2 lesions on brain and/or spinal cord
MRI AND

- 1 contrast-enhancing lesion or =1 new or enlarging T2 lesion on brain
and/or spinal cord MRI previous 12 month

- Previously treated RRMS patients:

1. =1 relapse previous 12 months OR

2. =1 contrast-enhancing lesion or =2 new/enlarging T2 lesions on brain and/or
spinal cord MRI previous 12 months

- Progressive MS patients:

1. =1 relapse previous 12 months OR

2. =1 contrast-enhancing lesion previous 12 months or =1 new/enlarging T2
lesions on brain and/or spinal cord MRI previous 12 months or =2 new or
enlarging T2 lesion on brain and/or spinal cord MRI previous 24 months OR

3. Increased levels of neurofilament light chain (NFL) in serum or
cerebrospinal fluid (CSF) in sample collected previous 12 months.
Progressive MS patients not fulfilling the clinical/MRI criteria for active
disease, may qualify for inclusion in the study if:

(A) CSF NFL level (measured with NF-Light® ELISA assay from Uman Diagnostics
or Simoa):

- 18 to 40 years >560 ng/l

- 41 to 60 years >890 ng/l

- 61 to 65 years >1850 ng/l

or

(B) Serum NFL level (measured with Simoa™ NF-light® Advantage Kit)

o Increased sNFL based on individual age-determined cut-off: >4.19 ×
1.029^age ng/L

OR

o Increased sNFL based age-partitioned cut-offs:

- 18 to 20 years >7.4 ng/L

- 21 to 30 years >9.9 ng/L

- 31 to 40 years >13.1 ng/L

- 41 to 50 years >17.5 ng/L

- 51 to 60 years >23.3 ng/L

- 61 to 65 years >30.9 ng/L

- Signed written informed consent

Exclusion Criteria:

- Pregnancy or breast feeding

- Lack of effective contraception for women of child-bearing potential (effective
contraception include oral contraception, intrauterine devices and other forms of
contraception with failure rate <1%)

- Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization

- Known active malignant disease

- Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled
cardiac disease

- Positive test for HIV, hepatitis B or C, or symptoms or signs of active tuberculosis
in a patient with a positive Quantiferon test.

- Negative test for varicella zoster

- Lymphopenia grade 2 (0.5 to 0.8 × 10^9/L) or higher grades of lymphopenia. In case of
switching from fingolimod, siponimod or ozanimod lymphopenia is accepted at screening
visit. Patients switching from dimethylfumarate who have persistent lymphopenia 5 to 6
weeks after stopping dimethylfumarate can be included if lymphopenia is grade 2 or
lower, and treating phycisian judge CD20-depleting therapy safe.

- Neutropenia grade 2 (1.0 to 1.5 × 10^9/L) or higher grades

- Thrombocytopenia grade 2 (50 to 75 × 10^9/L) or higher grades

- Previous treatment with alemtuzumab or hematopoietic stem-cell transplantation

- Previous treatment with cladribine, CD20-depleting antibodies, daclizumab or other
immune suppressive treatment which is judged to still exert immune suppressive effect
by treating physician

- Methylprednisolone treatment within 1 month of baseline visit

- Findings on the screening MRI judged to preclude participation by the treating
physician

- Other diseases judged to be relevant by the treating physician

- Contraindication to MRI

- Known allergy or hypersensitivity to rituximab or ocrelizumab



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Relapsing Remitting Multiple Sclerosis

Secondary Progressive Multiple Sclerosis

Primary Progressive Multiple Sclerosis

Intervention(s)

Drug: Fexofenadine

Drug: Rituximab

Drug: Ocrelizumab

Drug: Paracetamol

Drug: Methylprednisolone

Primary Outcome(s)

Percentage of patients without new or enlarging T2 white matter lesions on brain MRI scans [Time Frame: Month 6 to month 24]

Secondary Outcome(s)

Annualised relapse rate based on cumulative number of confirmed relapses from baseline to months 24 [Time Frame: Baseline to month 24]

Blood levels of cluster of differentiation antigen 19 (CD19)+ B cells [Time Frame: At month 6 and month 24]

Change in serum neurofilament light chain level [Time Frame: From baseline to month 24]

EuroQol- 5 Dimension (EQ-5D) [Time Frame: Baseline to month 24]

Percentage brain volume change (PBVC) from month 6 to month 24 [Time Frame: From month 6 to month 24]

Change in Multiple Sclerosis Impact Scale (MSIS-29) [Time Frame: Baseline to month 24]

Percentage of patients with 6-month confirmed disability progression (CDP) in Expanded Disability Status Scale (EDSS) [Time Frame: Baseline to month 24]

Percentage of patients with 6-months CDP in Symbol Digit Modalities Test (SDMT) [Time Frame: Baseline to month 24]

Change in T2 white matter lesion volume [Time Frame: From month 6 to month 24]

Percentage of patients with 6-months CDP in Timed 25 Foot Walk (T25FW) [Time Frame: Baseline to month 24]

Change in Fatigue Scale for Motor and Cognitive Functions (FSMC) [Time Frame: Baseline to month 24]

Change in T1 white matter lesion volume [Time Frame: From month 6 to month 24]

Percentage of patients with 6-months CDP in 9-Hole-Peg Test (9HPT) [Time Frame: Baseline to month 24]

Percentage of patients without gadolinium-enhancing lesions (GdEL) [Time Frame: Month 6 and month 24 MRI scans]

Secondary ID(s)

DanNORMS_version 3.2

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Kolding Sygehus

Herlev Hospital

Sanquin Research & Blood Bank Divisions

Aalborg University Hospital

Hospital of South West Jutland, Esbjerg, Denmark

Danske Regioner

GCP unit, Copenhagen University Hospital

Hillerod Hospital, Denmark

Hospital of Southern Jutland, Sønderborg, Denmark

Odense University Hospital

Hospital of Central Denmark Region, Viborg, Denmark

Hospital of Southern Jutland, Aabenraa, Denmark

Hvidovre University Hospital

Aarhus University Hospital

GCP-unit at Aarhus University Hospital, Aarhus, Denmark

Gødstrup Hospital