Myasthenia Gravis
Conditions
Keywords
IMVT-1401
Brief summary
The purpose of the current study is to assess safety/tolerability and key pharmacodynamic (PD) effects that are considered to be associated with clinical benefit (reduction of total IgG and anti-AChR-IgG) in Myasthenia Gravis patients following treatment with RVT-1401 (also known as IMVT-1401) compared to placebo.
Interventions
DRUGRVT-1401
Subcutaneous administration of RVT-1401
DRUGPlacebo
Subcutaneous administration of Placebo
Sponsors
Immunovant Sciences GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Blinded
Intervention model description
Randomized, Double-Blind, Placebo-Controlled Study with an Open-Label Extension
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female ≥ 18 years of age. 2. Myasthenia Gravis Foundation of America (MGFA) Class II-IVa and likely not in need of a respirator for the duration of the study as judged by the Investigator. 3. QMG score ≥12 at Screening and Baseline. Other, more specific inclusion criteria are defined in the protocol.
Exclusion criteria
1. Use of rituximab, belimumab, eculizumab or any monoclonal antibody for immunomodulation within 6 months prior to first dosing. 2. Immunoglobulins given by SC, IV (IVIG), or intramuscular route, or plasmapheresis/plasma exchange (PE) within 4 weeks before Screening. 3. Thymectomy performed \< 12 months prior to screening. 4. Total IgG level \<6 g/L (at screening). 5. Absolute neutrophil count \<1500 cells/mm3(at screening). Other, more specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double-Blind Treatment Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Week 18 | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. SAEs were defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the other outcomes listed in the definition. |
| Open-Label Extension Period: Number of Participants Reporting AEs and SAEs | Up to Week 18 | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration. SAEs were defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the other outcomes listed in the definition. |
| Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Vital Signs | Up to Week 7 | Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate and temperature were measured after resting for at least 5 minutes in a semi-supine position. |
| Open-label Extension Period: Number of Participants With Clinically Significant Changes in Vital Signs | Up to Week 18 | Vital signs including SBP, DBP, pulse rate and temperature were measured after resting for at least 5 minutes in a semi-supine position. |
| Double-blind Treatment Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | Up to Week 7 | Clinical laboratory parameters included clinical chemistry, hematology and urinalysis. |
| Open-label Extension Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | Up to Week 18 | Clinical laboratory parameters included clinical chemistry, hematology and urinalysis. |
| Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) | Up to Week 7 | Twelve-lead ECG was performed after 5 minutes of rest in the supine position. |
| Open-label Extension Period: Number of Participants With Clinically Significant Changes in ECG | Up to Week 18 | Twelve-lead ECG was performed after 5 minutes of rest in the supine position. |
| Double-blind Treatment Period: Percent Change From Baseline in Levels of Total Immunoglobulin G (IgG) | Baseline (Day 1) and Up to Week 7 | Serum samples were collected for the analysis of total immunoglobulin G. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7) minus the Baseline value, divided by the Baseline value x 100. |
| Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | Baseline (Day 1) and Up to Week 7 | Serum samples were collected for the analysis of IgG 1, 2, 3 and 4 levels. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7) minus the Baseline value, divided by the Baseline value x 100. |
| Double-Blind Treatment Period: Percent Change From Baseline in Anti-acetylcholine Receptor Immunoglobulin G (Anti-AChR-IgG) at Week 7 | Baseline (Day 1) and Week 7 | Serum samples were collected for the analysis of Anti-AChR-IgG. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7) minus the Baseline value, divided by the Baseline value x 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Double-Blind Treatment Period: Percentage of Participants With an Improvement on the MGC Score | Baseline (Day 1) to Week 7 | The response was defined as improvement (decrease) from Baseline on the MGC score by =\> 3 points. The MGC was developed by selecting the best performing items from 3 commonly used Myasthenia Gravis specific scales (QMG, Myasthenia Gravis manual muscle test, and MG-ADL) and is comprised of 10 functional domains: 3 ocular, 3 bulbar, 1 respiratory, 1 neck, and 2 limb items. The total score ranges from 0 (no myasthenic findings) to 50 (maximal myasthenic deficits). The scale measures symptoms and signs of MG in these domains incorporating both physician and participant-reported test items. Higher scores correlate with clinical worsening of the disease. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug. |
| Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Quality of Life 15 Revised Score (MG-QOL 15r) Score | Baseline (Day 1) and at Week 4 and Week 7 | The MG-QOL15r is a participant-reported questionnaire designed to assess how a participant's Myasthenia Gravis affects different aspects related to their quality of life. The scale includes 15 items that are graded on a scale of 0 to2; the total across is the sum of all 15 items and represents the MG-QOL15r score. The range of the MG-QOL15r score is 0 - 30. Higher scores indicate worse outcomes. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Double-Blind Treatment Period: Area Under the Concentration-time Curve From Time 0 to 168 Hours (AUC0-168h) of RVT-1401 | Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8 | Blood samples were collected for the analysis of Pharmacokinetic parameter AUC (0-168h). |
| Open-Label Extension Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies | Up to Week 18 | The serum levels of anti-RVT-1401 antibodies were determined. All samples that were potentially positive were analyzed with the confirmation assay where presence of anti-RVT-1401 was confirmed; the therapeutic antibody was used to compete with the analytical responses of ADA to assess specificity of screened positive samples. |
| Double-Blind Treatment Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies | Up to Week 7 | The serum levels of anti-RVT-1401 antibodies were determined. All samples that were potentially positive were analyzed with the confirmation assay where presence of anti-RVT-1401 was confirmed; the therapeutic antibody was used to compete with the analytical responses of anti-drug antibody (ADA) to assess specificity of screened positive samples. |
| Open-label Extension Period: AUC0-168h of RVT-1401 | Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8, Week 9, Week 12 and Week 14 | Pharmacokinetic parameters were not estimated because the sparse PK sampling schedule did not allow for accurate estimates of these parameters. |
| Double-Blind Treatment Period: Maximum Concentration (Cmax) of RVT-1401 | Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8 | Blood samples were collected for the analysis of Pharmacokinetic parameter Cmax. |
| Open-label Extension Period: Cmax of RVT-1401 | Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8, Week 9, Week 12 and Week 14 | Blood samples were collected for the analysis of Pharmacokinetic parameter Cmax. |
| Double-Blind Treatment Period: Trough Concentrations (Ctrough) of RVT-1401 | Pre-dose | Blood samples were planned to be collected at indicated time points to measure the concentration of RVT-1401 pre-dose (Ctrough) as an assessment of the pharmacokinetic RVT-1401. |
| Open-label Extension Period: Ctrough of RVT-1401 | Pre-dose | Blood samples were planned to be collected at indicated time points to measure the concentration of RVT-1401 pre-dose (Ctrough) as an assessment of the pharmacokinetic RVT-1401. |
| Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Baseline (Day 1) and at Week 2, Week 3, Week 4, Week 5, Week 6 (Day 36) and Week 7 | The QMG score is a physician-reported outcome measure was used to assess MG disease severity and pattern of deficits based on quantitative testing of affected muscle groups. The scale comprised of 13 test items that were graded on a scale of 0 (no myasthenic findings) to 3 (maximal myasthenic deficits). The total sum across all 13 items represents the QMG score. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the QMG Score From Baseline | Baseline (Day 1) to Week 7 | The response is defined as improvement from Baseline on the QMG score by =\> 3 points. The QMG score is a physician-reported outcome measure was used to assess MG disease severity and pattern of deficits based on quantitative testing of affected muscle groups. The scale comprised of 13 test items that were graded on a scale of 0 (no myasthenic findings) to 3 (maximal myasthenic deficits). The total sum across all 13 items represents the QMG score. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Baseline (Day 1) and at Week 2, Week 3, Week 4, Week 5, Week 6 (Day 36), Week 7 | The MG-ADL is an 8-item, participant-reported outcome measure that assessed Myasthenia Gravis symptoms and their effects on activities of daily living, with each response graded from 0 (normal) to 3 (most severe). The MG-ADL score was calculated by totaling the rating for each of the 8 items. Total MG-ADL scores range from 0 to 24 with higher scores indicating more severe disease. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the MG-ADL Score | Baseline (Day 1) to Week 7 | The response was defined as improvement (decrease) from Baseline on the MG-ADL score by =\> 2 points. The MG-ADL is an 8-item, participant-reported outcome measure that assessed Myasthenia Gravis symptoms and their effects on activities of daily living, with each response graded from 0 (normal) to 3 (most severe). The MG-ADL score was calculated by totaling the rating for each of the 8 items. Total MG-ADL scores range from 0 to 24 with higher scores indicating more severe disease. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug. |
| Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Baseline (Day 1) and at Week 2, Week 3, Week 4, Week 5, Week 6 (Day 36), Week 7 | The MGC was developed by selecting the best performing items from 3 commonly used Myasthenia Gravis specific scales (QMG, Myasthenia Gravis manual muscle test, and MG-ADL) and is comprised of 10 functional domains: 3 ocular, 3 bulbar, 1 respiratory, 1 neck, and 2 limb items. The total score ranges from 0 (no myasthenic findings) to 50 (maximal myasthenic deficits). The scale measures symptoms and signs of MG in these domains incorporating both physician and participant-reported test items. Higher scores correlate with clinical worsening of the disease. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
Countries
Canada, United States
Participant flow
Recruitment details
This was a Phase 2a, randomized, double-blind (DB), placebo-controlled study with an Open-Label Extension (OLE) that was designed to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of RVT-1401 versus placebo in acetylcholine receptor (AChR) antibody positive myasthenia gravis (MG) participants.
Pre-assignment details
A total of 17 participants were enrolled in the study. One participant completed the DB period and did not enter the OLE; this participant completed the 12-week post Double-blind Treatment Follow-up Period.
Participants by arm
| Arm | Count |
|---|---|
| Double-blind Treatment Period: Placebo Participants were randomized to receive Placebo during the 6-week double blind period. Participants who completed DB Treatment period entered an OLE where they received 340 mg RVT-1401 every 2 weeks (Q2W) x 3 doses, followed by a 6-week follow-up period where the participant did not receive any study treatment. | 6 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week Participants were randomized to receive 340 mg/week during the 6-week double blind period. Participants who completed DB Treatment period entered an OLE where they received 340 mg RVT-1401 Q2W x 3 doses, followed by a 6-week follow-up period where the participant did not receive any study treatment. Participants | 5 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week Participants were randomized to receive 680 mg/week during the 6-week double blind period. Participants who completed DB Treatment period entered an OLE where they received 340 mg RVT-1401 Q2W x 3 doses, followed by a 6-week follow-up period where the participant did not receive any study treatment. | 6 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Treatment Period (6 Weeks) | Adverse Event | 0 | 0 | 1 | 0 |
| Open Label Extension Period (12 Weeks) | Adverse Event | 0 | 0 | 0 | 3 |
| Open Label Extension Period (12 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | Double-blind Treatment Period: Placebo | Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: RVT-1401 680 mg/Week | Total |
|---|---|---|---|---|
| Age, Continuous | 41.0 Years STANDARD_DEVIATION 15.4 | 56.8 Years STANDARD_DEVIATION 22.17 | 70.8 Years STANDARD_DEVIATION 14.22 | 56.2 Years STANDARD_DEVIATION 20.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 5 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 6 Participants | 17 Participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 15 |
| other Total, other adverse events | 5 / 6 | 4 / 5 | 5 / 6 | 10 / 15 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 | 1 / 6 | 1 / 15 |
Outcome results
Primary
Double-Blind Treatment Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. SAEs were defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the other outcomes listed in the definition.
Time frame: Up to Week 18
Population: Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 5 Participants |
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 4 Participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 5 Participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 1 Participants |
Primary
Double-blind Treatment Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters
Clinical laboratory parameters included clinical chemistry, hematology and urinalysis.
Time frame: Up to Week 7
Population: Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-blind Treatment Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
Primary
Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)
Twelve-lead ECG was performed after 5 minutes of rest in the supine position.
Time frame: Up to Week 7
Population: Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) | 0 Participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) | 0 Participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) | 0 Participants |
Primary
Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate and temperature were measured after resting for at least 5 minutes in a semi-supine position.
Time frame: Up to Week 7
Population: Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Primary
Double-Blind Treatment Period: Percent Change From Baseline in Anti-acetylcholine Receptor Immunoglobulin G (Anti-AChR-IgG) at Week 7
Serum samples were collected for the analysis of Anti-AChR-IgG. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7) minus the Baseline value, divided by the Baseline value x 100.
Time frame: Baseline (Day 1) and Week 7
Population: Full Analysis Set. Only those participants with data available at definite timepoints has been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Percent Change From Baseline in Anti-acetylcholine Receptor Immunoglobulin G (Anti-AChR-IgG) at Week 7 | 15.92 Percent change | Standard Error 12.41 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Percent Change From Baseline in Anti-acetylcholine Receptor Immunoglobulin G (Anti-AChR-IgG) at Week 7 | -46.66 Percent change | Standard Error 13.64 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Percent Change From Baseline in Anti-acetylcholine Receptor Immunoglobulin G (Anti-AChR-IgG) at Week 7 | -85.28 Percent change | Standard Error 12.27 |
p-value: 0.0009ANCOVA
p-value: <0.0001ANCOVA
Primary
Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4
Serum samples were collected for the analysis of IgG 1, 2, 3 and 4 levels. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7) minus the Baseline value, divided by the Baseline value x 100.
Time frame: Baseline (Day 1) and Up to Week 7
Population: Full Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | IgG2 | -2.2 Percent change | Standard Error 5.35 |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | IgG1 | -3.3 Percent change | Standard Error 3.67 |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | IgG3 | -2.1 Percent change | Standard Error 4.69 |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | IgG4 | -3.1 Percent change | Standard Error 5.68 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | IgG4 | -48.0 Percent change | Standard Error 6.08 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | IgG2 | -54.7 Percent change | Standard Error 5.65 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | IgG3 | -68.2 Percent change | Standard Error 5.05 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | IgG1 | -65.9 Percent change | Standard Error 4.02 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | IgG3 | -82.9 Percent change | Standard Error 5.12 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | IgG2 | -63.6 Percent change | Standard Error 5.6 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | IgG1 | -76.3 Percent change | Standard Error 3.98 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4 | IgG4 | -64.7 Percent change | Standard Error 6.1 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Primary
Double-blind Treatment Period: Percent Change From Baseline in Levels of Total Immunoglobulin G (IgG)
Serum samples were collected for the analysis of total immunoglobulin G. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7) minus the Baseline value, divided by the Baseline value x 100.
Time frame: Baseline (Day 1) and Up to Week 7
Population: Full Analysis Set comprised of all randomized participants who received at least 1 dose of randomized study medication with at least 1 valid post-treatment value. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Percent Change From Baseline in Levels of Total Immunoglobulin G (IgG) | -3.17 Percent change | Standard Error 2.97 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: Percent Change From Baseline in Levels of Total Immunoglobulin G (IgG) | -59.49 Percent change | Standard Error 3.15 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-blind Treatment Period: Percent Change From Baseline in Levels of Total Immunoglobulin G (IgG) | -77.66 Percent change | Standard Error 2.92 |
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
Primary
Open-Label Extension Period: Number of Participants Reporting AEs and SAEs
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration. SAEs were defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the other outcomes listed in the definition.
Time frame: Up to Week 18
Population: Open-label Extension (OLE) Analysis Set comprised of all participants who enrolled in the OLE study phase and received at least 1 dose of study medication in the OLE. Participants were analyzed based on the randomization schedule, regardless of the treatment actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-blind Treatment Period: Placebo | Open-Label Extension Period: Number of Participants Reporting AEs and SAEs | Any AE | 10 Participants |
| Double-blind Treatment Period: Placebo | Open-Label Extension Period: Number of Participants Reporting AEs and SAEs | Any SAE | 1 Participants |
Primary
Open-label Extension Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters
Clinical laboratory parameters included clinical chemistry, hematology and urinalysis.
Time frame: Up to Week 18
Population: OLE Analysis Set. Participants were analyzed based on the randomization schedule, regardless of the treatment actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Open-label Extension Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Open-label Extension Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Open-label Extension Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
Primary
Open-label Extension Period: Number of Participants With Clinically Significant Changes in ECG
Twelve-lead ECG was performed after 5 minutes of rest in the supine position.
Time frame: Up to Week 18
Population: OLE Analysis Set. Participants were analyzed based on the randomization schedule, regardless of the treatment actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Open-label Extension Period: Number of Participants With Clinically Significant Changes in ECG | 0 Participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Open-label Extension Period: Number of Participants With Clinically Significant Changes in ECG | 0 Participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Open-label Extension Period: Number of Participants With Clinically Significant Changes in ECG | 0 Participants |
Primary
Open-label Extension Period: Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs including SBP, DBP, pulse rate and temperature were measured after resting for at least 5 minutes in a semi-supine position.
Time frame: Up to Week 18
Population: OLE Analysis Set. Participants were analyzed based on the randomization schedule, regardless of the treatment actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Open-label Extension Period: Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Open-label Extension Period: Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Open-label Extension Period: Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Secondary
Double-Blind Treatment Period: Area Under the Concentration-time Curve From Time 0 to 168 Hours (AUC0-168h) of RVT-1401
Blood samples were collected for the analysis of Pharmacokinetic parameter AUC (0-168h).
Time frame: Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8
Population: Pharmacokinetic (PK) Analysis Set comprised of all participants who underwent PK sampling and had evaluable concentration-time data for analysis. As PK analyses were not conducted, a PK Analysis Set was not presented.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Area Under the Concentration-time Curve From Time 0 to 168 Hours (AUC0-168h) of RVT-1401 | NA Hours*microgram per milliliter |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Area Under the Concentration-time Curve From Time 0 to 168 Hours (AUC0-168h) of RVT-1401 | NA Hours*microgram per milliliter |
Secondary
Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score
The MG-ADL is an 8-item, participant-reported outcome measure that assessed Myasthenia Gravis symptoms and their effects on activities of daily living, with each response graded from 0 (normal) to 3 (most severe). The MG-ADL score was calculated by totaling the rating for each of the 8 items. Total MG-ADL scores range from 0 to 24 with higher scores indicating more severe disease. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1) and at Week 2, Week 3, Week 4, Week 5, Week 6 (Day 36), Week 7
Population: Full Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 2 | -1.7 Scores on a scale | Standard Deviation 2.34 |
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 3 | -0.8 Scores on a scale | Standard Deviation 2.04 |
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 4 | -0.8 Scores on a scale | Standard Deviation 2.64 |
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 5 | -1.5 Scores on a scale | Standard Deviation 3.02 |
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 6 (Day 36) | -1.2 Scores on a scale | Standard Deviation 3.19 |
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 7 | -0.2 Scores on a scale | Standard Deviation 2.71 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 7 | -4.4 Scores on a scale | Standard Deviation 7.06 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 2 | -3.2 Scores on a scale | Standard Deviation 6.61 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 5 | -3.2 Scores on a scale | Standard Deviation 6.65 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 6 (Day 36) | -5.2 Scores on a scale | Standard Deviation 7.09 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 3 | -3.8 Scores on a scale | Standard Deviation 5.97 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 4 | -3.2 Scores on a scale | Standard Deviation 6.38 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 3 | -1.7 Scores on a scale | Standard Deviation 1.97 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 4 | -2.0 Scores on a scale | Standard Deviation 2.35 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 7 | -3.2 Scores on a scale | Standard Deviation 3.11 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 5 | -2.0 Scores on a scale | Standard Deviation 2.35 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 2 | -0.7 Scores on a scale | Standard Deviation 0.82 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score | Week 6 (Day 36) | -3.4 Scores on a scale | Standard Deviation 3.36 |
Secondary
Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score
The MGC was developed by selecting the best performing items from 3 commonly used Myasthenia Gravis specific scales (QMG, Myasthenia Gravis manual muscle test, and MG-ADL) and is comprised of 10 functional domains: 3 ocular, 3 bulbar, 1 respiratory, 1 neck, and 2 limb items. The total score ranges from 0 (no myasthenic findings) to 50 (maximal myasthenic deficits). The scale measures symptoms and signs of MG in these domains incorporating both physician and participant-reported test items. Higher scores correlate with clinical worsening of the disease. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1) and at Week 2, Week 3, Week 4, Week 5, Week 6 (Day 36), Week 7
Population: Full Analysis Set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 7 | -0.8 Scores on a scale | Standard Deviation 7.33 |
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 2 | -2.3 Scores on a scale | Standard Deviation 2.94 |
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 4 | -2.0 Scores on a scale | Standard Deviation 8.1 |
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 6 (Day 36) | -2.5 Scores on a scale | Standard Deviation 8.04 |
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 3 | -1.3 Scores on a scale | Standard Deviation 5.2 |
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 5 | -4.3 Scores on a scale | Standard Deviation 7.5 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 3 | -8.8 Scores on a scale | Standard Deviation 9.98 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 6 (Day 36) | -10.4 Scores on a scale | Standard Deviation 9.32 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 7 | -9.0 Scores on a scale | Standard Deviation 10.12 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 5 | -7.0 Scores on a scale | Standard Deviation 10.07 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 4 | -7.2 Scores on a scale | Standard Deviation 10.4 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 2 | -7.0 Scores on a scale | Standard Deviation 9.27 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 7 | -7.0 Scores on a scale | Standard Deviation 5.34 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 2 | -3.0 Scores on a scale | Standard Deviation 3.1 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 3 | -2.3 Scores on a scale | Standard Deviation 2.88 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 4 | -4.0 Scores on a scale | Standard Deviation 6.6 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 5 | -2.8 Scores on a scale | Standard Deviation 4.97 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score | Week 6 (Day 36) | -6.6 Scores on a scale | Standard Deviation 5.13 |
Secondary
Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Quality of Life 15 Revised Score (MG-QOL 15r) Score
The MG-QOL15r is a participant-reported questionnaire designed to assess how a participant's Myasthenia Gravis affects different aspects related to their quality of life. The scale includes 15 items that are graded on a scale of 0 to2; the total across is the sum of all 15 items and represents the MG-QOL15r score. The range of the MG-QOL15r score is 0 - 30. Higher scores indicate worse outcomes. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1) and at Week 4 and Week 7
Population: Full Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Quality of Life 15 Revised Score (MG-QOL 15r) Score | Week 4 | -3.5 Scores on a scale | Standard Deviation 3.83 |
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Quality of Life 15 Revised Score (MG-QOL 15r) Score | Week 7 | -2.3 Scores on a scale | Standard Deviation 3.93 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Quality of Life 15 Revised Score (MG-QOL 15r) Score | Week 7 | -6.6 Scores on a scale | Standard Deviation 10.55 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Quality of Life 15 Revised Score (MG-QOL 15r) Score | Week 4 | -6.0 Scores on a scale | Standard Deviation 9.77 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Quality of Life 15 Revised Score (MG-QOL 15r) Score | Week 4 | 1.6 Scores on a scale | Standard Deviation 5.03 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Quality of Life 15 Revised Score (MG-QOL 15r) Score | Week 7 | 2.0 Scores on a scale | Standard Deviation 4.42 |
Secondary
Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score
The QMG score is a physician-reported outcome measure was used to assess MG disease severity and pattern of deficits based on quantitative testing of affected muscle groups. The scale comprised of 13 test items that were graded on a scale of 0 (no myasthenic findings) to 3 (maximal myasthenic deficits). The total sum across all 13 items represents the QMG score. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1) and at Week 2, Week 3, Week 4, Week 5, Week 6 (Day 36) and Week 7
Population: Full Analysis Set. Only those participants with data available at specified time points has been represented (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 2, n=6,5,6 | -3.3 Scores on a scale | Standard Deviation 2.16 |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 3, n=6,5,6 | -2.5 Scores on a scale | Standard Deviation 2.74 |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 7, n=5,5,5 | -1.8 Scores on a scale | Standard Deviation 3.27 |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 4, n=6,5,5 | -2.7 Scores on a scale | Standard Deviation 2.73 |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 5, n=6,5,5 | -2.7 Scores on a scale | Standard Deviation 2.73 |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 6 (Day 36), n=6,5,5 | -3.0 Scores on a scale | Standard Deviation 3.22 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 5, n=6,5,5 | -3.2 Scores on a scale | Standard Deviation 6.8 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 6 (Day 36), n=6,5,5 | -4.0 Scores on a scale | Standard Deviation 6.75 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 4, n=6,5,5 | -3.6 Scores on a scale | Standard Deviation 6.43 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 2, n=6,5,6 | -2.8 Scores on a scale | Standard Deviation 5.36 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 7, n=5,5,5 | -4.0 Scores on a scale | Standard Deviation 6.82 |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 3, n=6,5,6 | -4.6 Scores on a scale | Standard Deviation 7.7 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 7, n=5,5,5 | -3.8 Scores on a scale | Standard Deviation 4.76 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 2, n=6,5,6 | -1.7 Scores on a scale | Standard Deviation 3.14 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 4, n=6,5,5 | -3.6 Scores on a scale | Standard Deviation 4.16 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 5, n=6,5,5 | -3.2 Scores on a scale | Standard Deviation 3.7 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 6 (Day 36), n=6,5,5 | -4.4 Scores on a scale | Standard Deviation 3.71 |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score | Week 3, n=6,5,6 | -2.5 Scores on a scale | Standard Deviation 2.95 |
Secondary
Double-Blind Treatment Period: Maximum Concentration (Cmax) of RVT-1401
Blood samples were collected for the analysis of Pharmacokinetic parameter Cmax.
Time frame: Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8
Population: Pharmacokinetic Analysis Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Maximum Concentration (Cmax) of RVT-1401 | NA micrograms per milliliter |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Maximum Concentration (Cmax) of RVT-1401 | NA micrograms per milliliter |
Secondary
Double-Blind Treatment Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies
The serum levels of anti-RVT-1401 antibodies were determined. All samples that were potentially positive were analyzed with the confirmation assay where presence of anti-RVT-1401 was confirmed; the therapeutic antibody was used to compete with the analytical responses of anti-drug antibody (ADA) to assess specificity of screened positive samples.
Time frame: Up to Week 7
Population: Full Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies | 2 Participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies | 1 Participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies | 1 Participants |
Secondary
Double-Blind Treatment Period: Percentage of Participants With an Improvement on the MGC Score
The response was defined as improvement (decrease) from Baseline on the MGC score by =\> 3 points. The MGC was developed by selecting the best performing items from 3 commonly used Myasthenia Gravis specific scales (QMG, Myasthenia Gravis manual muscle test, and MG-ADL) and is comprised of 10 functional domains: 3 ocular, 3 bulbar, 1 respiratory, 1 neck, and 2 limb items. The total score ranges from 0 (no myasthenic findings) to 50 (maximal myasthenic deficits). The scale measures symptoms and signs of MG in these domains incorporating both physician and participant-reported test items. Higher scores correlate with clinical worsening of the disease. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug.
Time frame: Baseline (Day 1) to Week 7
Population: Full Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Percentage of Participants With an Improvement on the MGC Score | 40.0 Percentage of participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Percentage of Participants With an Improvement on the MGC Score | 60.0 Percentage of participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Percentage of Participants With an Improvement on the MGC Score | 60.0 Percentage of participants |
Secondary
Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the MG-ADL Score
The response was defined as improvement (decrease) from Baseline on the MG-ADL score by =\> 2 points. The MG-ADL is an 8-item, participant-reported outcome measure that assessed Myasthenia Gravis symptoms and their effects on activities of daily living, with each response graded from 0 (normal) to 3 (most severe). The MG-ADL score was calculated by totaling the rating for each of the 8 items. Total MG-ADL scores range from 0 to 24 with higher scores indicating more severe disease. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug.
Time frame: Baseline (Day 1) to Week 7
Population: Full Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the MG-ADL Score | 33.3 Percentage of participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the MG-ADL Score | 60.0 Percentage of participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the MG-ADL Score | 60.0 Percentage of participants |
Secondary
Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the QMG Score From Baseline
The response is defined as improvement from Baseline on the QMG score by =\> 3 points. The QMG score is a physician-reported outcome measure was used to assess MG disease severity and pattern of deficits based on quantitative testing of affected muscle groups. The scale comprised of 13 test items that were graded on a scale of 0 (no myasthenic findings) to 3 (maximal myasthenic deficits). The total sum across all 13 items represents the QMG score. QMG total scores range from 0 to 39 for a given visit, with higher scores indicating more severe disease. Baseline was defined as the last non-missing value prior to the date (time) of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1) to Week 7
Population: Full Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the QMG Score From Baseline | 20.0 Percentage of participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the QMG Score From Baseline | 40.0 Percentage of participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the QMG Score From Baseline | 60.0 Percentage of participants |
Secondary
Double-Blind Treatment Period: Trough Concentrations (Ctrough) of RVT-1401
Blood samples were planned to be collected at indicated time points to measure the concentration of RVT-1401 pre-dose (Ctrough) as an assessment of the pharmacokinetic RVT-1401.
Time frame: Pre-dose
Population: Pharmacokinetic Analysis Set. Participants were analyzed based on the randomization schedule, regardless of the treatment actually received.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Double-Blind Treatment Period: Trough Concentrations (Ctrough) of RVT-1401 | NA Milligrams per liter |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Double-Blind Treatment Period: Trough Concentrations (Ctrough) of RVT-1401 | NA Milligrams per liter |
Secondary
Open-label Extension Period: AUC0-168h of RVT-1401
Pharmacokinetic parameters were not estimated because the sparse PK sampling schedule did not allow for accurate estimates of these parameters.
Time frame: Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8, Week 9, Week 12 and Week 14
Population: Pharmacokinetic Analysis Set. Participants were analyzed based on the randomization schedule, regardless of the treatment actually received.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Open-label Extension Period: AUC0-168h of RVT-1401 | NA Hours*microgram per milliliter |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Open-label Extension Period: AUC0-168h of RVT-1401 | NA Hours*microgram per milliliter |
Secondary
Open-label Extension Period: Cmax of RVT-1401
Blood samples were collected for the analysis of Pharmacokinetic parameter Cmax.
Time frame: Pre-dose; Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29, Day 36, Day 38, Day 40, Week 7, Week 8, Week 9, Week 12 and Week 14
Population: Pharmacokinetic Analysis Set. Participants were analyzed based on the randomization schedule, regardless of the treatment actually received.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Open-label Extension Period: Cmax of RVT-1401 | NA Micrograms per milliliter |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Open-label Extension Period: Cmax of RVT-1401 | NA Micrograms per milliliter |
Secondary
Open-label Extension Period: Ctrough of RVT-1401
Blood samples were planned to be collected at indicated time points to measure the concentration of RVT-1401 pre-dose (Ctrough) as an assessment of the pharmacokinetic RVT-1401.
Time frame: Pre-dose
Population: Pharmacokinetic Analysis Set. Participants were analyzed based on the randomization schedule, regardless of the treatment actually received.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Open-label Extension Period: Ctrough of RVT-1401 | NA Milligrams per liter |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Open-label Extension Period: Ctrough of RVT-1401 | NA Milligrams per liter |
Secondary
Open-Label Extension Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies
The serum levels of anti-RVT-1401 antibodies were determined. All samples that were potentially positive were analyzed with the confirmation assay where presence of anti-RVT-1401 was confirmed; the therapeutic antibody was used to compete with the analytical responses of ADA to assess specificity of screened positive samples.
Time frame: Up to Week 18
Population: Full Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind Treatment Period: Placebo | Open-Label Extension Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies | 1 Participants |
| Double-blind Treatment Period: RVT-1401 340 mg/Week | Open-Label Extension Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies | 0 Participants |
| Double-blind Treatment Period: RVT-1401 680 mg/Week | Open-Label Extension Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies | 0 Participants |