Safety,Tolerability,Pharmacokinetics and Efficacy of CFZ533 in Moderate to Severe Myasthenia Gravis

NCT02565576 | Completed Phase 2 Results DMC

• 1 other identifier: CCFZ533X2204
• Study Type: interventional
• Target: 44
• Locations: 5 countries
• Sites: 15

Brief Summary

The purpose of this study is to evaluate safety, tolerability, pharmacokinetics/pharmacodynamics and efficacy of CFZ533 as an add-on therapy to standard of care in patients with moderate to severe myasthenia gravis (MG).

Conditions

Myasthenia Gravis, Generalized

Keywords

CFZ533, Myasthenia Gravis

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in the Quantitative Myastenia Gravis (QMG) Score at Week 25. Posterior Median Was Used as Measure Type.

  QMG score is an established validated measure of disease severity used in MG trials (Jaretzki et al 2000). The scoring system is based on quantitative testing of sentinel muscle groups by means of a 4 point scale ranging from 0 (no symptoms) to 3 (severe symptoms). The scale measures ocular, bulbar, respiratory, and limb function, grading each finding, and the total score ranges from 0 (no myasthenic findings) to 39 (maximal myasthenic deficits) (Sharshar et al 2000, Bedlack et al 2005).

  week 25

Secondary Outcomes (10)

• Mean Changes From Baseline in the Myasthenia Gravis Composite (MGC) Score. Posterior Median Was Used as Measure Type.

  From baseline to week 49

• Proportion of Patients With Improvement or Worsening by ≥ 3 Points in the QMG Score

  at week 49

• Proportion of Patients Intolerant to Steroid Taper

  week 49

• Number of Patients Who Discontinued Due to Inefficacy or Worsening

  week 49

• Mean Change From Baseline in the Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL)

  week 25

Study Arms (2)

CFZ533

ACTIVE COMPARATOR

CFZ533

Drug: Placebo; Drug: CFZ533

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Placebo DRUG

CFZ533; Placebo

CFZ533 DRUG

CFZ533

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of MG class IIa to IVa inclusive (Myasthenia Gravis Foundation of America Clinical Classification).
• Quantitative Myasthenia Gravis (QMG) score of 10 or greater. If the QMG score is \< 15 no more than 4 points may be derived from items 1 or 2 (ocular motility disturbance and ptosis).
• Documented history of acetylcholine receptor (AChR) or Muscle Specific Kinase (MuSK) antibody positive.
• 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 12 weeks after study treatment.

You may not qualify if:

• 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 thehalf-life, whichever is longer.
• Live vaccines within 4 weeks of study drug infusion.
• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Novartis Investigative Site

Montreal, Quebec, H3A 2BA, Canada

Location

Novartis Investigative Site

Québec, Quebec, G1J 1Z4, Canada

Location

Novartis Investigative Site

Aarhus, 8000 C, Denmark

Location

Novartis Investigative Site

Copenhagen, 2100, Denmark

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Halle/S, 06120, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Novartis Investigative Site

Samara, Samara Oblast, 443095, Russia

Location

Novartis Investigative Site

Barnaul, 656024, Russia

Location

Novartis Investigative Site

Kazan', 420021, Russia

Location

Novartis Investigative Site

Novosibirsk, 630087, Russia

Location

Novartis Investigative Site

S-Petersburg, 194354, Russia

Location

Novartis Investigative Site

Tainan, Taiwan ROC, 70403, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Taipei, Taiwan

Location

Related Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

iscalimab

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2015
• First Posted: October 1, 2015
• Study Start: September 29, 2015
• Primary Completion: July 31, 2017
• Study Completion: December 19, 2017
• Last Updated: January 5, 2021
• Results First Posted: July 25, 2019

Record last verified: 2019-07

Locations

DE (3); RU (5); DK (2); CA (2); TW (3)