A Study of RVT-1401 in Myasthenia Gravis (MG) Patients

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.

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.

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.

Vital signs including SBP, DBP, pulse rate and temperature were measured after resting for at least 5 minutes in a semi-supine position.

Clinical laboratory parameters included clinical chemistry, hematology and urinalysis.

Clinical laboratory parameters included clinical chemistry, hematology and urinalysis.

Twelve-lead ECG was performed after 5 minutes of rest in the supine position.

Twelve-lead ECG was performed after 5 minutes of rest in the supine position.

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.

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.

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.

Blood samples were collected for the analysis of Pharmacokinetic parameter AUC (0-168h).

Pharmacokinetic parameters were not estimated because the sparse PK sampling schedule did not allow for accurate estimates of these parameters.

Blood samples were collected for the analysis of Pharmacokinetic parameter Cmax.

Blood samples were collected for the analysis of Pharmacokinetic parameter Cmax.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.