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

• Register: EUCTR
• Last refreshed on: 3 December 2024
• Main ID: EUCTR2020-004505-32-IT
• Date of registration: 12/10/2021
• Prospective Registration: No
• Primary sponsor: NOVARTIS PHARMA AG
• Public title: 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
• Scientific title: An Open-Label, Rater-Blind, Randomized, Multi-Center, Parallel-Arm, Active-Comparator Study to Assess the Efficacy and Tolerability of Ofatumumab 20mg SC monthly vs. First Line DMT - physician’s choice in the treatment of newly diagnosed RMS (STHENOS) - STHENOS
• Date of first enrolment: 24/09/2021
• Target sample size: 236
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004505-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Rater-Blind If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Italy, Spain

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA S.p.A

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA S.p.A

Key inclusion & exclusion criteria

Inclusion criteria:
• Written informed consent obtained before any assessment
• Male/female patients, 18 through 45 (inclusive) years of age
• Diagnosis of MS according to the 2017 revised McDonald criteria
• Relapsing MS: relapsing-course (RMS), as defined by Lublin et al 2014
• Treatment Naïve patients, = 3 years since first MS symptom
• EDSS score: 0–3 (inclusive)
• Patient must be suitable to be treated with one of first line selfadministered DMT physician's choice (glatiramer acetate, IFNs, teriflunomide or DMF, according to EMA SmPC) or ofatumumab depending on randomization and physician's choice
•At least 1 relapse or 1 Gd+ enhanced lesion on T1 in the year prior to Screening
• Able to obtain MRI assessment

Please see protocol for complete detailed list of inclusion criteria
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 236
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Diseases other than multiple sclerosis responsible for the clinical or MRI presentation
• Progressive MS phenotypes: Patients with primary progressive MS or SPMS
• Use of other experimental or investigational drugs
• Relapse between Screening and Baseline visits
• Pregnancy or breastfeeding
• Patients suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the Investigator
• Women of childbearing potential defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception (methods that result in less than 1% pregnancy rates) 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
• Patients with an active chronic disease (or stable but treated with immune therapy) of the immune system other than MS or with immunodeficiency syndrome
• Patients with a chronic active infection until the infection is resolved. Where local regulation requires it, Sars-Cov-19 must be ruled out by the PCR test
• Patients with neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML), or confirmed PML
• Patients at risk of developing or having reactivation of hepatitis
• Patients at risk of developing or having reactivation of syphilis or tuberculosis (e.g. patients with known exposure to, or history of syphilis, or active or latent tuberculosis, even if previously treated). Testing for syphilis, HIV and tuberculosis will be done at Screening according to local clinical practice
• Have received any live or live-attenuated vaccines within 4 weeks prior to first study drug administration
• 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
• Conditions or treatments that may impact the safety of the patient
• Abnormal laboratory values as confirmed by the central laboratory
prior to first study drug administration
• Patients with severe hypoproteinemia e.g. in nephrotic syndrome
• Patients with any of the following 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
• History of hypersensitivity to the study drug or any of the excipients or to drugs of similar chemical classes

Please see protocol for complete detailed list of exclusion criteria


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple Sclerosis
MedDRA version: 20.0 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: COPAXONE - 20 MG/ML SOLUZIONE INIETTABILE 28 SIRINGHE PRERIEMPITE
Product Name: COPAXONE
Product Code: [-]
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: glatiramer acetato
Current Sponsor code: -
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: Rebif
Product Name: Rebif
Product Code: [-]
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: interferone beta-1a
Current Sponsor code: -
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 44-

Trade Name: Rebif
Product Name: rebif
Product Code: [-]
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: interferone beta-1a
Current Sponsor code: -
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 44-

Trade Name: plegridy
Product Name: plegridy
Product Code: [-]
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: peginterferone beta 1a
Current Sponsor code: -
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 125-

Trade Name: Avonex
Product Name: Avonex
Product Code: [-]
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Interferone beta 1a
Current Sponsor code: -
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 30-

Trade Name: Extavia
Product Name: Extavia
Product Code: [-]
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: interferone beta-1b
Current Sponsor code: -
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 250-

Trade Name: COPAXONE - "40 MG/ML SOLUZIONE INIETTABILE IN

Primary Outcome(s)

Secondary Objective: - Evaluate the efficacy to therapy of ofatumumab vs first line selfadministered DMTs (physician's choice) in newly diagnosed/naïvetreated RMS patient population
- Evaluate the safety and tolerability of ofatumumab vs first line selfadministered DMTs (physician's choice) in newly diagnosed/naïvetreated RMS patient population

Timepoint(s) of evaluation of this end point: At Month 15

Primary end point(s): • 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

Main Objective: 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 Outcome(s)

Secondary end point(s): • Number of relapses
• Annual Relapse Rate (ARR)
• Mean time to first relapse
• Proportion of relapse-free patients at Month 3, 9 and 15
• 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
• Time to 3-month Confirmed Disability Worsening (3mCDW)
• Time to 6-month Confirmed Disability Worsening (6mCDW)
• Change in expanded disability status scale (EDSS) from baseline to end of study
• Proportion of disability progression free patient at EoS
• Number of Gadolinium enhancing (Gd+) T1 lesions of brain
• Volume of Gd+ T1 lesions of brain
• Number of new/enlarging T2 lesions of brain
• Volume of new/enlarging T2 lesions of brain
• Proportion of SAEs, and SAEs with hospitalizations between ofatumumab 20 mg s.c. and first line self-administered DMTs
• Proportion of patients with adverse events, including injection related reactions
• Proportion of patients who withdrew due to abnormal lab values
• Proportion of treatment discontinuation or interruptions for safety/ tolerability reason
• Compliance to treatment using patient diary

Timepoint(s) of evaluation of this end point: At Months 3, 6, 9, 12 and 15. For full details, please refer to the assessment schedule in the protocol.

Secondary ID(s)

2020-004505-32-FR

COMB157G3301

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 15/09/2021
Contact: