Open Label Randomized Multicenter to Assess Efficacy & Tolerability of Ofatumumab 20mg vs. First Line DMT in RMS (STHENOS)

  • STATUS
    Recruiting
  • End date
    Jul 15, 2024
  • participants needed
    236
  • sponsor
    Novartis Pharmaceuticals
Updated on 27 June 2022
interferon
MRI
disease or disorder
glatiramer acetate
dimethyl fumarate
teriflunomide

Summary

This study will compare ofatumumab vs. European approved platform first line self-administered disease modifying therapy (DMT) in newly diagnosed MS patients

Description

The study is a randomized (1:1), open-label, rater-blind, multi-center, prospective, parallel-arm, active comparator study which will consist of 15 months treatment period and a 6 months observational safety extension period in 236 total patients with early relapsing multiple sclerosis (RMS) RMS patients are patients who are newly diagnosed or have never been on active treatment at the time of study entry with ≤ 3 years from first MS symptoms.

There is a screening period and patients are randomized to either ofatumumab or first line DMT at baseline. Patients will be treated until the end of study (EOS) or for a maximum duration of 15 months. Patients who prematurely discontinue study drug or comparator will have their end of treatment (EOT) visit and assessments at the time of discontinuation. After ofatumumab or the standard of care comparator (DMT) discontinuation, patients may initiate alternative MS therapy according to local standard of care, if clinically indicated.

Patients who for any reason withdraw from ofatumumab during treatment will be invited to participate in the observational extension safety period for 6 months or until patient re-starts MS treatment with a new DMT treatment. During this period, clinical efficacy after ofatumumab withdrawal will be assessed.

Details
Condition Multiple Sclerosis
Treatment Ofatumumab, First line DMT
Clinical Study IdentifierNCT04788615
SponsorNovartis Pharmaceuticals
Last Modified on27 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Male/female patients, 18 through 45 (inclusive) years of age
Written informed consent obtained before any assessment
Diagnosis of MS according to the 2017 revised McDonald criteria (Thompson et al 2018)
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 self-administered DMT-physician's choice (glatiramer acetate, IFNs, teriflunomide, DMF according to EMA SmPC) or ofatumumab depending on randomization and physician's choice
At least 1 relapse or 1 Gd+ enhanced lesion on T1in the year prior to Screening
Able to obtain MRI assessment

Exclusion Criteria

Diseases other than multiple sclerosis responsible for the clinical or MRI presentation
Progressive MS phenotypes: Patients with primary progressive MS (Polman et al 2011) or SPMS (Lublin et al 2014)
Use of other experimental or investigational drugs at the time of enrollment (Screening) or within the prior 30 days, or 5 elimination half-lives, or until the expected pharmacodynamics effect has returned to baseline, whichever is longer
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
Highly effective methods of contraception include
Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant
(Vasectomized partner is a highly effective birth control method provided that partner
is the sole sexual partner of the WOCBP trial participant and that the vasectomized
partner has received medical assessment of the surgical success.)
Use of combined, estrogen and progesterone containing (oral, intravaginal
transdermal), hormonal methods of contraception or use of progesterone-only
(oral, injectable, implantable) hormonal methods of contraception or placement of
an intrauterine device (IUD) or intrauterine system (IUS), or other forms of
hormonal contraception that have comparable efficacy (failure rate <1%), for
example hormone vaginal ring or transdermal hormone contraception. In case of use
of oral contraception women should have been stable on the same pill for a
minimum of 3 months before taking study treatment. Women are considered
post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea
with an appropriate clinical profile (e.g. age appropriate history of vasomotor
symptoms). Women are considered not of childbearing potential if they are
post-menopausal or have had surgical bilateral oophorectomy (with or without
hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks
ago. In the case of oophorectomy alone, only when the reproductive status of the
woman has been confirmed by follow up hormone level assessment is she considered
not of childbearing potential. If local regulations deviate from the
contraception methods listed above to prevent pregnancy, local regulations apply
and will be described in the ICF
Patients with an active chronic disease (or stable but treated with immune therapy) of
the immune system other than MS (e.g. rheumatoid arthritis, scleroderma, Sjögren's
syndrome, Crohn's disease, ulcerative colitis, etc.) or with immunodeficiency syndrome
(hereditary immune deficiency, drug-induced immune deficiency)
Patients with a chronic active infection (bacterial, fungal, or viral like hepatitis
HIV or COVID), 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. Positive results
at Screening for serological markers for hepatitis (H) A, B, C, and E indicating acute
or chronic infection: - anti-HA Immunoglobulin M (IgM)
HBs Ag and/or anti-HBc IgM and/or HB virus deoxyribonucleic acid (DNA)
anti-HBs negative and Anti-HBc positive
anti-HC IgG (if positive IgG, HCV-RNA PCR will be performed and if negative
patient can be enrolled)
anti-HE IgM (if positive IgG and/or IgM, perform HE-RNA PCR and if negative
patient can be enrolled) NOTE: If the Investigator suspects false positive
hepatitis serology results such as an antibody pattern indicating acute hepatitis
infection but no corresponding elevated liver enzymes and no signs or symptoms of
liver disease, an infectious disease expert may be consulted. In the case the
patient has a record of vaccination including HB, and there is no evidence of
acute or chronic hepatitis infection (confirmed by an infectious disease expert)
the Investigator must document (in source data and as a comment in the electronic
Case Report Form (eCRF)) that the serology results are considered false positive
and may then enroll the patient
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
Any of the following conditions or treatments that may impact the safety of the
patient
History of, or current, significant cardiac disease including cardiac failure (NYHA
functional class II-IV), myocardial infarction (within 6 months prior to screening)
unstable angina (within 6 months prior to screening), transient ischemic attack
(within 6 months prior to screening), stroke, cardiac arrhythmias requiring treatment
or uncontrolled arterial hypertension
Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular
tachycardia and clinically significant second or third degree AV block without a
pacemaker on screening electrocardiogram (ECG)
History of or active severe respiratory disease, including Chronic Obstructive
Pulmonary Disease, interstitial lung disease or pulmonary fibrosis
Patients with asthma requiring regular treatment with oral steroids
Severe hepatic impairment (Child-Pugh class C) or any chronic liver or biliary
disease
Patients with severe renal impairment (glomerular filtration rate < 30 ml/min/1.73
m2)
Any medically unstable condition as determined by the Investigator
Any of the following abnormal laboratory values as confirmed by the central laboratory
prior to first study drug administration: - Total or direct bilirubin greater than 3
times upper limit of normal (ULN) range, unless in the context of Gilbert's syndrome
Alkaline phosphatase (ALP) greater than 5 times the ULN range
Alanine aminotransferase (ALT) between 1.5 and 5 times the ULN range and an
active infection with hepatotropic viruses (Herpes simplex virus, Cytomegalovirus
and Epstein-Barr Virus)
Serum IgG < 500mg/dL (according to central laboratory range)
Any other clinically significant laboratory assessment as determined by the
Investigator (e.g. significant anemia, neutropenia, thrombocytopenia, signs of
impaired bone marrow function)
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
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