Long-term safety, tolerability and effectiveness study of ofatumumab in subjects with relapsing multiple sclerosis

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2017-004703-51-ES
• Date of registration: 25/10/2018
• Prospective Registration: Yes
• Primary sponsor: Novartis Farmacéutica, S.A
• Public title: Long-term safety, tolerability and effectiveness study of ofatumumab in subjects with relapsing multiple sclerosis
• Scientific title: An open-label, single arm, multi-center extension study evaluating long-term safety, tolerability and effectiveness of ofatumumab in subjects with relapsing multiple sclerosis
• Date of first enrolment: 31/01/2019
• Target sample size: 2233
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004703-51
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Latvia, Lithuania, Mexico, Netherlands, Norway, Peru, Poland, Portugal, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Trial Monitoring Organization (TMo)
• Affiliation: Novartis Farmacéutica, S.A

• Name: Trial Monitoring Organization (TMo)
• Affiliation: Novartis Farmacéutica, S.A

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for inclusion in this study must fulfill all of the following criteria:
1. Must have participated in a Novartis MS study:
• which dosed ofatumumab 20 mg sc every 4 weeks,
• was an adult (= 18 years of age) study in RMS,
• must have completed the study on study treatment (subjects that are on temporary drug interruption at the time of End of Study are considered completers).
2. Written informed consent must be obtained before any assessment is performed
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 2233
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Premature discontinuation from previous ofatumumab study or from study treatment in previous ofatumumab study
2.Subjects that have had their previous ofatumumab study EOS > 6 months prior to screening and/or been given another MS DMT between EOS of previous study and screening of this study
3.Less than 3.5-month washout of teriflunomide for subjects that will not complete the accelerated elimination procedure (AEP) prior to Day 1. Only applicable to subjects completing studies COMB157G2301 and COMB157G2302
4.Subjects with a history of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the Investigator
5.Subjects that have any unresolved adverse event or condition from the previous study that necessitates temporary interruption of the study treatment, until such time as the event or condition has resolved (the subject will be monitored within the safety follow-up of the previous study during this time)
6.Emergence of any clinically significant condition/disease during previous ofatumumab study in which study participation might result in safety risk for subjects
7. Subjects with neurological findings consistent with PML or confirmed PML
8.Subjects with active systemic bacterial, viral or fungal infections, or chronic infection (e.g. Acquired Immune Deficiency Syndrome (AIDS))
9. Subjects that have developed or have had reactivation of syphilis or tuberculosis during previous ofatumumab study
10. Subjects with severe hypoproteinemia e.g. nephrotic syndrome
11. Any of the following abnormal laboratory values prior to Day 1:
- Total or conjugated bilirubin (BIL) greater than 1.5 times the upper limit of normal (ULN) range
- Alkaline phosphatase (ALP) greater than 2 times the ULN range
- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) greater than 3 times ULN
- Any other clinically significant laboratory assessment as determined by the Investigator (e.g. significant anemia, neutropenia, thrombocytopenia, signs of impaired bone marrow function)


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

Health Condition(s) or Problem(s) studied

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

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

Intervention(s)

Trade Name: Arzerra
Product Name: ofatumumab
Product Code: OMB157
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: OFATUMUMAB
CAS Number: 679818-59-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): • Proportion of subjects with adverse events
• Proportion of subjects with laboratory, vital signs, or electrocardiogram (ECG) results meeting abnormal criteria
• Proportion of subjects meeting predefined criteria in Columbia Suicide Severity Rating Scale (C-SSRS)

Timepoint(s) of evaluation of this end point: 5 years after LPFV

Main Objective: Evaluate the long-term safety and tolerability of ofatumumab 20 mg sc once every 4 weeks in subjects with relapsing MS from the first dose of ofatumumab

Secondary Objective: 1. Describe long-term efficacy of ofatumumab 20 mg sc once every 4 weeks in subjects with relapsing MS (RMS) from the first dose of ofatumumab

2. For subjects originally in COMB157G2301 and COMB157G2302 compare long-term outcomes in those who were immediately treated with ofatumumab versus delayed use of ofatumumab (i.e. after teriflunomide treatment in the COMB157G2301 and COMB157G2302 studies), by analyzing subjects according to their randomized treatment in COMB157G2301 and COMB157G2302

3. For subjects randomized to teriflunomide in COMB157G2301 and COMB157G2302 and switched to ofatumumab in the COMB157G2399 compare both periods before and after the switch to ofatumumab

4. Explore the long-term health outcomes in subjects with RMS treated with ofatumumab 20 mg sc once every 4 weeks from the first dose of ofatumumab

Secondary Outcome(s)

Secondary end point(s): • Annualized Relapse Rate (ARR)
• Time to first relapse
• Time to 3-month Confirmed Disability Worsening (3mCDW)
• Time to 6-month Confirmed Disability Worsening (6mCDW)
• Time to 6-month Confirmed Disability Improvement (6mCDI)
• Time to 12-month Confirmed Disability Improvement (12mCDI)
• Time to 24-month Confirmed Disability Improvement (24mCDI)
• Time to 6-month Confirmed Disability Improvement (6mCDI) sustained until End of Study (EOS)
• Change in Expanded Disability Status Scale (EDSS)
• Time to 6-month confirmed 4-point worsening on Symbol Digit Modalities Test (SDMT)
• Change in SDMT
• Annualized T2 lesion rate
• Number of T1 Gd-enhancing lesions per Magnetic Resonance Image (MRI) scan
• Annual rate of change in brain volume
• Change in NfL concentration in serum
• Relationship between NFL and disease activity, disease course and treatment response
• Patient Reported Outcomes (PRO)

Timepoint(s) of evaluation of this end point: Up to 5 years

Secondary ID(s)

COMB157G2399

2017-004703-51-DE

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date:
Contact: