Myasthenia Gravis, GeneralizedPhase 2NCT02565576
Safety,Tolerability,Pharmacokinetics and Efficacy of CFZ533 in Moderate to Severe Myasthenia Gravis
A Phase 2 study testing CFZ533 in people with Myasthenia Gravis, Generalized, run by Novartis Pharmaceuticals at 15 sites in 5 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Myasthenia Gravis, Generalized
- What is being tested?
- CFZ533
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 15 sitesin 5 countries
- Study dates
- 29 Sep 2015to 19 Dec 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 14Show fewer
- 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).
Trial locations and contacts
15 sites in 5 countries.
15 sites in 5 countries
Russia5 sites
Novartis Investigative Site
Barnaul, 656024
Novartis Investigative Site
Kazan', 420021
Novartis Investigative Site
Novosibirsk, 630087
Novartis Investigative Site
S-Petersburg, 194354
Novartis Investigative Site
Samara, Samara Oblast, 443095
Germany3 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Halle/S, 06120
Novartis Investigative Site
München, 81377
Taiwan3 sites
Novartis Investigative Site
Tainan, Taiwan ROC, 70403
Novartis Investigative Site
Taipei, 10002
Novartis Investigative Site
Taipei
Canada2 sites
Novartis Investigative Site
Montreal, Quebec, H3A 2BA
Novartis Investigative Site
Québec, Quebec, G1J 1Z4
Denmark2 sites
Novartis Investigative Site
Aarhus, 8000 C
Novartis Investigative Site
Copenhagen, 2100
About this study
Official 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
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
- Being tested
- Placebo, CFZ533
- Keywords
- CFZ533, Myasthenia Gravis
- Medical subject headings
- Myasthenia Gravis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
CFZ533Drug
| Study group | Role | What they receive |
|---|---|---|
| CFZ533 | Active comparator | CFZ533 Receives: Drug: Placebo; Drug: CFZ533 |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: week 25
Secondary outcomes (10)
Mean Changes From Baseline in the Myasthenia Gravis Composite (MGC) Score. Posterior Median Was Used as Measure Type.
The Myasthenia Gravis Composite (MGC) score is another key efficacy outcome measure, ranging from 0 to 50. It is reliable and demonstrates concurrent and longitudinal construct validity in the MG practice care setting (Burns et al 2010). The MGC scale covers 10 important functional domains most frequently involved in patients with MG. The proportion of bulbar and respiratory items reflect the clinical importance of these domains in the disease, and are appropriately weighted.
The assessment of each of the 10 test items provides immediate insight into the status of that particular functional domain. A decrease in this score shows an improvement.
Measured: From baseline to week 49
Proportion of Patients With Improvement or Worsening by ≥ 3 Points in the QMG Score
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).
Measured: at week 49
Proportion of Patients Intolerant to Steroid Taper
Measured: week 49
Number of Patients Who Discontinued Due to Inefficacy or Worsening
Measured: week 49
Mean Change From Baseline in the Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL)
The MG-ADL is an 8-item survey to assess functional performance of daily activities that are sometimes impaired by MG e.g. talking, breathing, swallowing etc. (Muppidi et al 2011). The higher score on MG-ADL scale (0-24 points) indicates worse functional performance of daily activities.
Measured: week 25
Mean Changes From Baseline in the QMG Score at Week 49
QMG (quantitative myasthenia gravis) 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). A decrease in the QMG score indicated an improvement. Results given as a change in the score as compared from baseline
Measured: week 49
Mean Change From Baseline in the Myasthenia Gravis Quality of Life (MG QOL-15)
The MG-QOL15 is a 15-item survey, completed by MG patients and it is designed to assess some aspects of quality of life (QoL) related to MG (Burns et al 2011) e.g. assesment of mood, eating, speaking, driving a car etc.. The higher score on MG-QOL15 scale (0-60 points) indicates worse QoL.
Measured: week 25
Free CD40 on B Cells
CD40 receptor occupancy by CFZ533 in peripheral blood was assessed by flow cytometry analysis, measuring free or total CD40 receptors on whole blood B cells. Free CD40 on CD19-positive B cells, using PE-conjugated CFZ533 whose binding was prevented by bound, unconjugated CFZ533 (drug bound to CD40 on peripheral blood B cells). The more CD40 was occupied by unlabeled CFZ533, the less binding of labeled CFZ533, manifest as a lower mean fluorescence intensity (MFI) of CD40 on B cells. MFI from free CD40 on B cells was converted into Molecules of Equivalent Soluble Fluorochrome (MESF) using PE-MESF beads.
Measured: week 1, week 25
Total Soluble CD40 (sCD40) in Plasma
PD
Measured: week1, week 25
Plasma CFZ533 Concentration at Steady State Conditions (Week 17)
Measured: week 17
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2015 (estimated)
- Study start29 Sep 2015
- Primary completion31 Jul 2017
- Study completion19 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myasthenia Gravis, GeneralizedStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02565576
- Sponsor's protocol ID
- CCFZ533X2204
- Status last verified
- Jul 2019
- First submitted
- 23 Jun 2015
- Last updated
- 5 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02565576
- Acronym / sponsor ID
- CCFZ533X2204
- Conditions
- Myasthenia Gravis, Generalized
- Keywords
- CFZ533, Myasthenia Gravis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 29 Sep 2015 (actual)
- Primary completion
- 31 Jul 2017 (actual)
- Study completion
- 19 Dec 2017 (actual)
- First posted
- 1 Oct 2015 (estimated)
- Results
- Posted 25 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CFZ533 | Active comparator | Drug: Placebo, Drug: CFZ533CFZ533 |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (14 listed)
- 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:
- Patients who are at significant risk for TE as judged by the investigator or have any one of the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo | Drug | CFZ533, Placebo |
| CFZ533 | Drug | CFZ533 |
Primary outcome
Mean Change From Baseline in the Quantitative Myastenia Gravis (QMG) Score at Week 25. Posterior Median Was Used as Measure Type.
Time frame: week 25
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).
10 secondary outcomes
Mean Changes From Baseline in the Myasthenia Gravis Composite (MGC) Score. Posterior Median Was Used as Measure Type.
Time frame: From baseline to week 49
Proportion of Patients With Improvement or Worsening by ≥ 3 Points in the QMG Score
Time frame: at week 49
Proportion of Patients Intolerant to Steroid Taper
Time frame: week 49
Number of Patients Who Discontinued Due to Inefficacy or Worsening
Time frame: week 49
Mean Change From Baseline in the Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL)
Time frame: week 25
Mean Changes From Baseline in the QMG Score at Week 49
Time frame: week 49
Mean Change From Baseline in the Myasthenia Gravis Quality of Life (MG QOL-15)
Time frame: week 25
Free CD40 on B Cells
Time frame: week 1, week 25
Total Soluble CD40 (sCD40) in Plasma
Time frame: week1, week 25
Plasma CFZ533 Concentration at Steady State Conditions (Week 17)
Time frame: week 17
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novartisclinicatrials.comLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CFZ533 in people with Myasthenia Gravis, Generalized, run by Novartis Pharmaceuticals at 15 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Russia, Germany, Taiwan, Canada, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change From Baseline in the Quantitative Myastenia Gravis (QMG) Score at Week 25. Posterior Median Was Used as Measure Type. (time frame: week 25). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2021.