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

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

ClinicalTrials.gov Identifier: NCT04788615

Novartis Reference Number: COMB157G3301

Last Update: Sep 14, 2022

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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

Condition 
Multiple Sclerosis
Phase 
Phase 3
Overall status 
Recruiting
Start date 
Jul 23, 2021
Completion date 
Jul 15, 2024
Gender 
All
Age(s)
18 Years - 55 Years (Adult)

Interventions

Drug
Ofatumumab
20mg Subcutaneous injection
Drug
First line DMT
any one of these based on availability at country given as First line DMT Glatiramer acetate 20mg or 40mg or Interferon 22µg or 0.25mg or Peg-Interferon beta-1a 63µg or 125µg or Teriflunomide 14mg or Dimethyl fumarate 120mg or 240mg or Diroximel fumarate 231mg or 462mg

Eligibility Criteria

Inclusion Criteria

Written informed consent obtained before any assessment
Male/female patients, 18 through 55 (inclusive) years of age.
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, ≤ 5 years since first MS symptom.
EDSS score 0-4.0 (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 T1 in 1 year prior to Screening.
Able to obtain MRI assessment.
Neurologically stable within 1 month prior to first study drug administration 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 an 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

Positive results at Screening for serological markers for hepatitis (H) B and C indicating acute or chronic infection: - Hepatitis B virus (HBV) screening should be performed before initiation of treatment.

At a minimum, screening should include hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) testing. These can be complemented with other appropriate markers as per local guidelines. Patients with positive hepatitis B serology (either HBsAg or HBcAb) should consult a liver disease expert before the start of treatment and should be monitored and managed following local medical standards to prevent hepatitis B reactivation.

- Hepatitis C risk must be ruled out via anti-HC IgG (if positive IgG, HCV-RNA PCR will be performed 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 subject.

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 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

Study Locations

France
Novartis Investigative Site
Recruiting
Bayonne, 64109
Bayonne Cedex
France
Novartis Investigative Site
Recruiting
Nantes, 44093
Cedex 1
France
Novartis Investigative Site
Recruiting
Amiens, 80054
-
France
Novartis Investigative Site
Recruiting
Bordeaux Cedex, 33076
-
France
Novartis Investigative Site
Recruiting
Clermont-Ferrand Cedex 1, 63003
-
France
Novartis Investigative Site
Recruiting
Creteil, 94010
-
France
Novartis Investigative Site
Recruiting
Gonesse, 95500
-
France
Novartis Investigative Site
Recruiting
Grenoble, 38042
-
France
Novartis Investigative Site
Recruiting
Lille Cedex, 59037
-
France
Novartis Investigative Site
Recruiting
Montpellier, 34295
-
France
Novartis Investigative Site
Recruiting
Nice Cedex, 06202
-
France
Novartis Investigative Site
Recruiting
Nimes, 30029
-
France
Novartis Investigative Site
Recruiting
Poissy, 78303
-
France
Novartis Investigative Site
Recruiting
Rennes Cedex, 35033
-
France
Novartis Investigative Site
Recruiting
Strasbourg, 67098
-
France
Novartis Investigative Site
Recruiting
Suresnes, 92150
-
France
Germany
Novartis Investigative Site
Recruiting
Bayreuth, 95445
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 12101
-
Germany
Novartis Investigative Site
Recruiting
Dortmund, 44137
-
Germany
Novartis Investigative Site
Recruiting
Heidelberg, 69120
-
Germany
Novartis Investigative Site
Recruiting
Kassel, 34121
-
Germany
Novartis Investigative Site
Recruiting
Siegen, 57076
-
Germany
Novartis Investigative Site
Recruiting
Ulm, 89073
-
Germany
Novartis Investigative Site
Recruiting
Ulm, 89081
-
Germany
Novartis Investigative Site
Recruiting
Westerstede/Oldenburg, 26655
-
Germany
Italy
Novartis Investigative Site
Recruiting
Montichiari, 25018
BS
Italy
Novartis Investigative Site
Recruiting
Milano, 20132
MI
Italy
Novartis Investigative Site
Recruiting
Roma, 00133
RM
Italy
Novartis Investigative Site
Recruiting
Roma, 00189
RM
Italy
Spain
Novartis Investigative Site
Recruiting
Malaga, 29010
Andalucia
Spain
Novartis Investigative Site
Recruiting
Sevilla, 41017
Andalucia
Spain
Novartis Investigative Site
Recruiting
Salt, 17190
Cataluna
Spain
Novartis Investigative Site
Recruiting
Santiago de Compostela, 15706
Galicia
Spain
Novartis Investigative Site
Recruiting
El Palmar, 30120
Murcia
Spain
Novartis Investigative Site
Recruiting
Baracaldo, 48903
Vizcaya
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08035
-
Spain
Novartis Investigative Site
Recruiting
Madrid, 28009
-
Spain
Novartis Investigative Site
Recruiting
Madrid, 28034
-
Spain
Novartis Investigative Site
Recruiting
Madrid, 28040
-
Spain
Novartis Investigative Site
Recruiting
Valencia, 46026
-
Spain
Novartis Investigative Site
Recruiting
Zaragoza, 50009
-
Spain
United Kingdom
Novartis Investigative Site
Recruiting
Exeter, EX2 5DW
-
United Kingdom
Novartis Investigative Site
Recruiting
Glasgow, G51 4TF
-
United Kingdom

Contacts

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Phone: 

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