Myasthenia Gravis
Conditions
Brief summary
The purpose of this study is to assess how well nipocalimab works when compared to efgartigimod in participants with generalized myasthenia gravis (a condition in which body's immune system mistakenly attacks and damages the connection between nerves and muscles causing muscle weakness).
Interventions
DRUGNipocalimab
Nipocalimab will be administered intravenously.
DRUGEfgartigimod
Efgartigimod will be administered intravenously.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
For all arms: * Medically stable on the basis of physical examination, medical history, vital signs, clinical laboratory tests, and 12-lead electrocardiogram (ECG) performed at screening * Diagnosis of myasthenia gravis (MG) with generalized muscle weakness meeting the clinical criteria for generalized MG (gMG) as defined by the Myasthenia gravis foundation of America (MGFA) clinical classification class II a/b, III a/b, or IV a/b at screening and positive for acetylcholine receptor (AChR) antibodies * Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of greater than or equal to (\>=) 5 with less than (\<) 50% of symptoms coming from ocular MG-ADL sub-scores at study screening and baseline (Day 1) visits Criteria specific to Arms 1 and 2 only: \- Has suboptimal response to current stable therapy for gMG according to the investigator or has discontinued corticosteroids and/or immunosuppressants/immunomodulators including eculizumab or other novel approved immune agents at least 4 weeks prior to baseline due to intolerance or lack of efficacy Criteria specific to Arm 3: \- Treatment with efgartigimod IV or subcutaneous (SC) for \>=1 cycle, and the final cycle is consistent with product information
Exclusion criteria
* Any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her gMG, or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant * Had a thymectomy within 1 year prior to baseline, or thymectomy is planned during the study * Currently has a malignancy or has a history of malignancy within 3 years before baseline Criteria specific to Arms 1 and 2 only: \- Has received treatment for MG with an FcRn-targeting therapy Criteria specific to Arm 3 only: \- Is currently taking IgG monoclonal antibody therapeutics, or Fc-conjugated therapeutic agents, including factor or enzyme replacement, with the exception of efgartigimod
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Arms 1 and 2: Averaged Mean Percent Change from Baseline in Total Immunoglobulin G (IgG) Levels Over Weeks 8, 10 and 12 | Baseline, Weeks 8, 10 and 12 | Average mean percent change from baseline in total IgG levels over Weeks 8 , 10 and 12 will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Arms 1 and 2: Averaged Mean Change from Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Total Score Over Weeks 8, 10 and 12 | Baseline, Weeks 8, 10 and 12 | Average mean change from baseline in MG-ADL total score over Weeks 8, 10 and 12 will be reported. The MG-ADL provides a rapid assessment of the participant's MG symptom severity. Eight functions (talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to arise from a chair, double vision, eyelid droop) are rated on a 4-point scale: 0 (no impairment) to 3 (severe impairment). The total score will be sum of eight function scores and can range from 0 to 24. A higher score indicates greater symptom severity. |
| Arms 1 and 2: Mean Percent Change from Baseline in Total IgG Between Arm 1 at EoT and Arm 2 at EoC Based on Clinical Evaluation | Baseline, EoT (for Arm 1) and EoC (Arm 2) up to Week 12 | Mean percent change from baseline in total IgG between Arm 1 at end of treatment (EoT) and Arm 2 at end of cycle (EoC) based on clinical evaluation will be reported. EoC based on clinical evaluation is defined as the timepoint at which after completion of one cycle of efgartigimod, based on MG-ADL score clinical criteria, the treatment decision would be made to start a second cycle of efgartigimod, an MG rescue medication, or Week 12/EoT, whichever occurs first. |
| Arms 1 and 2: Mean Percent Change from Baseline in MG-ADL Total Score Between Arm 1 at EoT and Arm 2 at EoC Based on Clinical Evaluation | Baseline, EoT (for Arm 1) and EoC (Arm 2) up to Week 12 | Mean change from baseline in MG-ADL total score between Arm 1 at EoT and Arm 2 at EoC based on clinical evaluation will be reported. MG-ADL provides a rapid assessment of the participant's MG symptom severity. The total score can range from 0 to 24. A higher score indicates greater symptom severity. |
| Arms 1 and 2: Mean Percent Change from Baseline in Total IgG Levels at Week 8 | Baseline and Week 8 | Mean percent change from baseline in total IgG levels at Week 8 will be reported. |
| Arms 1 and 2: Mean Change from Baseline in MG-ADL Total Score at Week 8 | Baseline and Week 8 | Mean change from baseline in MG-ADL total score at Week 8 will be reported. MG-ADL provides a rapid assessment of the participant's MG symptom severity. The total score can range from 0 to 24. A higher score indicates greater symptom severity. |
| Arms 1 and 2: Averaged Mean Change from Baseline in Quantitative Myasthenia Gravis (QMG) Total Score Over Weeks 8 and 12 | Baseline, Weeks 8 and 12 | Average mean change from baseline in QMG total score over Weeks 8 and 12 will be reported. The QMG test is a standardized quantitative strength assessment comprising 13 components. The quantitative results of each strength component are mapped to the following 4-point scale: 0 = None, 1 = Mild, 2 = Moderate and 3 = Severe. The total score can range from 0 to 39. A higher score indicates greater weakness. |
| Arms 1 and 2: Mean Percent Change from Baseline in QMG Total Score Between Arm 1 at EoT and Arm 2 at EoC Based on Clinical Evaluation | Baseline, EoT (for Arm 1) and EoC (Arm 2) up to Week 12 | Mean change from baseline in QMG total score between Arm 1 at EoT and Arm 2 at EoC based on clinical evaluation will be reported. The QMG test is a standardized quantitative strength assessment comprising 13 components. The quantitative results of each strength component are mapped to the following 4-point scale: 0 = None, 1 = Mild, 2 = Moderate and 3 = Severe. The total score can range from 0 to 39. A higher score indicates greater weakness. |
| Arms 1 and 2: Mean Change from Baseline in QMG Total Score at Week 8 | Baseline and Week 8 | Mean change from baseline in QMG total score at Week 8 will be reported. |
| Arms 1 and 2: Percentage of Participants Maintaining >= 2-Point Improvement in MG-ADL Total Score for At Least 6 Weeks During Randomized Treatment Phase | Baseline up to Week 12 | Percentage of participants maintaining \>= 2-point improvement in MG-ADL total score for at least 6 weeks during the 12 week randomized treatment phase between Arms 1 and 2 will be reported. MG-ADL provides a rapid assessment of the participant's MG symptom severity. The total score can range from 0 to 24. A higher score indicates greater symptom severity. |
| Arms 1 and 2: Percentage of Participants Maintaining >= 2-Point Improvement in MG-ADL Total Score for At Least 8 Weeks During Randomized Treatment Phase | Baseline up to Week 12 | Percentage of participants maintaining \>= 2-point improvement in MG-ADL total score for at least 8 weeks during the 12 week randomized treatment phase between Arms 1 and 2 will be reported. MG-ADL provides a rapid assessment of the participant's MG symptom severity. The total score can range from 0 to 24. A higher score indicates greater symptom severity. |
| Arms 1 and 2: Percentage of Participants Maintaining >= 2-Point Improvement in MG-ADL Total Score for 50% of Postbaseline Observations | Baseline, Week 2 up to Week 12 | Percentage of participants maintaining \>= 2-point improvement in MG-ADL total score for at least 50% of study duration between Arms 1 and 2 will be reported. MG-ADL provides a rapid assessment of the participant's MG symptom severity. The total score can range from 0 to 24. A higher score indicates greater symptom severity. |
| Arms 1 and 2: Percentage of Participants Maintaining >= 2-Point Improvement in MG-ADL Total Score for 75% of Postbaseline Observations | Baseline, Week 2 up to Week 12 | Percentage of participants maintaining \>= 2-point improvement in MG-ADL for at least 75% of study duration between Arms 1 and 2 will be reported. |
| Arms 1 and 2: Percentage of Participants with MG-ADL Total Score of 0 or 1 at Week 12 | Week 12 | Percentage of participants with MG-ADL total score of 0 or 1 at end of study treatment between Arms 1 and 2 will be reported. MG-ADL provides a rapid assessment of the participant's MG symptom severity. The total score can range from 0 to 24. A higher score indicates greater symptom severity. |
| Arm 3: Mean Percent Change in Total IgG from Switch Day 1 to Switch Week 12 | Switch Day 1 to Switch Week 12 | Mean percent change in total IgG from pre-nipocalimab exposure to end of nipocalimab study treatment in Arm 3 will be reported. |
| Arm 3: Mean Change in MG-ADL Total Score from Switch Day 1 to Switch Week 12 | Switch Day 1 to Switch Week 12 | Mean change in MG-ADL total score from pre-nipocalimab exposure to end of nipocalimab study treatment in Arm 3 will be reported. MG-ADL provides a rapid assessment of the participant's MG symptom severity. The total score can range from 0 to 24. A higher score indicates greater symptom severity. |
| Arm 3: Percentage of Participants with >= 2-Point Improvement in MG-ADL Total Score at Switch Week 12 | At Switch Week 12 | Percentage of participants with \>= 2-point improvement in MG-ADL total score at switch week 12 in Arm 3 will be reported. |
| Arm 3: Percentage of Participants Maintaining >= 2-Point Improvement in MG-ADL Total Score for At Least 6 Weeks During Treatment Phase | Switch Day 1 up to Switch Week 12 | Percentage of participants maintaining \>= 2-point improvement in MG-ADL total score while on nipocalimab for at least 6 weeks during treatment phase in Arm 3 will be reported. MG-ADL provides a rapid assessment of the participant's MG symptom severity. The total score can range from 0 to 24. A higher score indicates greater symptom severity. |
| Arm 3: Percentage of Participants with MG-ADL Total Score of 0 or 1 at Switch Week 12 | At Switch Week 12 | Percentage of participants with MG-ADL total score of 0 or 1 at switch week 12 in Arm 3 will be reported. MG-ADL provides a rapid assessment of the participant's MG symptom severity. The total score can range from 0 to 24. A higher score indicates greater symptom severity. |
| Arms 1 and 2: Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | Up to Week 20 | An AE is any untoward medical occurrence in a clinical study participant administered with a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product and is medically important. Treatment-emergent AEs associated with a. infections that are severe or require IV anti-infective or operative/invasive intervention, b. events of hypoalbuminemia \<20 g/L and c. serious and non-serious venous thromboembolism (VTE; deep vein thrombosis \[DVT\] and/or pulmonary embolism \[PE\]) will be considered AESIs. |
| Arm 3: Number of Participants with AEs, SAEs and AESIs | Up to Switch Week 20 | An AE is any untoward medical occurrence in a clinical study participant administered with a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product and is medically important. Treatment-emergent AEs associated with a. infections that are severe or require IV anti-infective or operative/invasive intervention, b. events of hypoalbuminemia \<20 g/L and c. serious and non-serious venous thromboembolism (VTE; DVT and/or PE) will be considered AESIs. |
Countries
Israel, United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed