Safety, tolerability and efficacy of CFZ533 in the treatment of moderate to severe myasthenia gravis patients

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2015-000097-35-DK
• Date of registration: 16/06/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Safety, tolerability and efficacy of CFZ533 in the treatment of moderate to severe myasthenia gravis patients
• Scientific title: A multi-center, randomized, double-blind, placebo-controlled, parallel group study to preliminarily evaluate the safety, tolerability, pharmacokinetics and efficacy of CFZ533 in patients with moderate to severe myasthenia gravis - Safety,tolerability,pharmacokinetics and efficacy of CFZ533 in moderate to severe myasthenia gravis
• Date of first enrolment: 03/09/2015
• Target sample size: 44
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000097-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Denmark, Germany, Russian Federation, Taiwan

Contacts

• Name: Klinisk forskningsafdeling
• Affiliation: Novartis Healthcare A/S

• Name: Klinisk forskningsafdeling
• Affiliation: Novartis Healthcare A/S

Key inclusion & exclusion criteria

Inclusion criteria:
• Diagnosis of MG class IIa to IVa inclusive (Myasthenia Gravis Foundation of America Clinical Classification).
• Quantitative Myasthenia Gravis (QMG) score of 10 or greater, with at least 4 points not derived from items 1 or 2 (ocular motility disturbance and ptosis).
• Presence of acetylcholine receptor (AChR) or Muscle Specific Kinase (MuSK) autoantibodies based on medical history and confirmed by
autoantibodies diagnostic test performed at screening.
• Only one immunosuppressant or immunomodulatory drug at a stable dose is allowed during the study (i) azathioprine and mycophenolate mofetil must be stable for at least 4 months prior to randomization (ii) cyclosporine must be
stable for at least 3 months prior to randomization.
If the patient is on oral corticosteroids, methotrexate or tacrolimus at screening, the dose must be stable for at least 1 month prior to randomization.
• If the patient is on cholinesterase inhibitors at screening, the dose must be stable for at least 2 weeks prior to randomization.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, may be included in the study if they are using highly effective methods of contraception during the study and for 6 months after study treatment.
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 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
• MGFA grade I, IVb, or V disease.
• Documented presence of unresected thymoma.
• Patients having undergone thymectomy or thymo thymectomy (resection of thymoma) within 6 months of screening.
• Patients having received any of the following treatments prior to randomization:
IVIg or plasma exchange within 8 weeks oral or IV cyclosphosphamide treatment within 3 months; IV corticosteroid bolus (dose higher than 1 mg/kg) within 3 months; belimumab within 6 months. For patients who received belimumab earlier, B cell count should be within normal range; rituximab within 12 months. For patients who received rituximab earlier, B cell count should be within normal range; any other biologic or an investigational drug within 1 month or five times the half-life, whichever is longer.
• Live vaccines within 4 weeks prior to randomization.
• Patients who are at significant risk for TE as judged by the investigator or have any one of the following:
- History of either thrombosis or 3 or more spontaneous abortions with or
- without the presence of anti-cardiolipin autoantibodies;
• Presence of prolonged partial thromboplastin time (PTT).


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

Health Condition(s) or Problem(s) studied

Acquired myasthenia gravis (MG) is an autoimmune disease that leads to fluctuating muscle weakness and fatigue. In the most common cases, muscle weakness is caused by circulating antibodies that bind to acetylcholine receptors at the postsynaptic neuromuscular junction, inhibiting the excitatory effects of the neurotransmitter acetylcholine.
MedDRA version: 19.0 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Code: CFZ533
Pharmaceutical Form: Powder for solution for injection/infusion
Other descriptive name: CFZ533
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: • To evaluate the safety and tolerability of CFZ533 as an add-on therapy to standard of care in moderate to severe MG patients.
• To evaluate the efficacy of IV CFZ533 as an add-on therapy to standard of care in patients with moderate to severe MG after 24 weeks of treatment.

Secondary Objective: • To evaluate the efficacy of CFZ533 throughout the 24 weeks treatment period
and the decay in efficacy throughout the 24 weeks follow-up period.
• To evaluate changes in patient’s quality of life (QOL) throughout 24 weeks
the treatment period.
• To evaluate the pharmacokinetics of CFZ533
• To evaluate the pharmacodynamics of CFZ533
• To assess immunogenicity of CFZ533

Primary end point(s): • Mean change from baseline in the QMG Score for Disease Severity after 24 weeks of treatment (primary endpoint).

Timepoint(s) of evaluation of this end point: After 24 weeks of treatment

Secondary Outcome(s)

Secondary end point(s): • Mean Change from baseline in QMG Score and MGC Score..
• Proportion of patients with improvement by = 3 points in QMG score.
• Proportion of patients with worsening by = 3 points in QMG score.
• Proportion of patients intolerant to steroid taper.
• Proportion of patients who discontinued due to inefficacy or worsening.
• Mean change from baseline in the MG-ADL and MG QOL-15.
• Free CFZ533 in plasma
• Free CD40 on B cells, total CD40 on B cells and total soluble CD40 in plasma
• Quantitative analysis of anti-CFZ533 antibodies in plasma

Timepoint(s) of evaluation of this end point: Throughout the study

Secondary ID(s)

CCFZ533X2204

2015-000097-35-DE

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 28/12/2018
• Date Completed: 19/12/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000097-35/results