Study of efficacy and tolerability of ofatumumab vs. First Line disease modifying treatment (DMT) - physician’s choice in the treatment of newly diagnosed relapsing multiple sclerosis (RMS) patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

23 Jul 2021 → 5 Nov 2025

Decision date (initial)

2024-07-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG ORG-100003908

External identifiers

EU CT number

2023-507431-37-00

EudraCT number

2020-004505-32

ClinicalTrials.gov

NCT04788615

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of ofatumumab vs first line physician’s choice DMTs for self administration in newly diagnosed/ treatment naïve RMS patient population at Month 15

Secondary objectives 2

1. Evaluate the efficacy to therapy of ofatumumab vs first line self-administered DMTs (physician’s choice) in newly diagnosed/naïve-treated RMS patient population
2. Evaluate the safety and tolerability of ofatumumab vs first line self-administered DMTs (physician’s choice) in newly diagnosed/naïve-treated RMS patient population

Conditions and MedDRA coding

relapsing multiple sclerosis (RMS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Written informed consent obtained before any assessment
2. Male/female patients, 18 through 55 (inclusive) years of age.
3. Diagnosis of MS according to the 2017 revised McDonald criteria (Thompson et al. 2018).
4. Relapsing MS: relapsing-course (RMS), as defined by Lublin et al 2014.
5. Treatment Naïve patients, ≤ 5 years since first MS symptom.
6. EDSS score: 0–4.0 (inclusive).
7. Patient must be suitable to be treated with one of first line self-administered DMT physician’s choice (glatiramer acetate, IFNs, teriflunomide or DMF, according to EMA SmPC) or ofatumumab depending on randomization and physician’s choice.
8. At least 1 relapse or 1 Gd+ enhanced lesion on T1 in 1 year prior to Screening.
9. Able to obtain MRI assessment.
10. Neurologically stable within 1 month prior to first study drug administration

Exclusion criteria 18

1. Diseases other than multiple sclerosis responsible for the clinical or MRI presentation
2. Relapse between Screening and Baseline visits
3. Pregnancy or breastfeeding
4. Patients suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the Investigator
5. Women of childbearing potential defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while receiving ofatumumab and for 6 months after the last administration. The requirements for contraception for the comparators should also be taken into consideration according to their SmPC.
6. Patients with an active chronic disease (or stable but treated with immune therapy) of the immune system other than MS or with immunodeficiency syndrome
7. Patients with an active infection until the infection is resolved. Where local regulation requires it, SARS-Cov-19 must be ruled out by the PCR test.
8. Patients with severe hypoproteinemia e.g. in nephrotic syndrome
9. Patients with neurologic/psychiatric disorders prior to first study drug administration • Score “yes” on item 4 or item 5 of the Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale (CSSRS) if this ideation occurred in the past 6 months OR • “yes” on any item of the Suicidal Behavior section, except for the “Non-Suicidal Self-Injurious Behavior” (item also included in the Suicidal Behavior section) if this behavior occurred in the past 2 years.
10. Patients with neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML), or confirmed PML
11. Positive results at Screening for serological markers for hepatitis B and C
12. Have received any live or live-attenuated vaccines within 4 weeks prior to first study drug administration
13. Any other disease or condition that could interfere with participation in the study according to the study protocol, or with the ability of the patients to cooperate or comply with the study procedures
14. Conditions or treatments that may impact the safety of the patient
15. Abnormal laboratory values as confirmed by the central laboratory prior to first study drug administration
16. Progressive MS phenotypes
17. Use of other experimental or investigational drugs
18. History of hypersensitivity to the study drug or any of the excipients or to drugs of similar chemical classes

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. NEDA-3 status (yes or no) NEDA-3 is defined as: 1. Absence of confirmed clinical relapse 2. Absence of new MRI activity (Gd+ T1 lesion or new/enlarged T2 lesion) with MRI re-baselined at Month 3 3. Absence of 3-month confirmed disability worsening

Secondary endpoints 18

1. Number of relapses up to Month 15/ EOS
2. Annual Relapse Rate (ARR)
3. Mean time to first relapse
4. Proportion of relapse-free patients at Month 3, 9 and 15
5. Proportion of relapse-free patients with MRI activity-free (no new Gd+ T1 lesion or new/enlarged T2 lesion) at Month 3, 9 and 15
6. Time to 3-month Confirmed Disability Worsening (3mCDW)
7. Time to 6-month Confirmed Disability Worsening (6mCDW)
8. Change in expanded disability status scale (EDSS) from Baseline to end of study
9. Proportion of disability progression free patient at EOS
10. Number of Gadolinium enhancing (Gd+) T1 lesions of brain
11. Volume of Gd+ T1 lesions of brain
12. Number of new/enlarging T2 lesions of brain
13. Volume of new/enlarging T2 lesions of brain
14. Proportion of SAEs, and SAEs with hospitalizations between ofatumumab 20 mg s.c. and first line self-administered DMTs
15. Proportion of patients with adverse events, including injection related reactions
16. Proportion of patients who withdrew due to abnormal lab values
17. Proportion of treatment discontinuation or interruptions for safety/ tolerability reason
18. Compliance to treatment using patient diary

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 11

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 25

Locations

4 EU/EEA countries · 39 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 37 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications