Neoplasms

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Symptoms and General Pathology

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Myasthenia Gravis

Muscle Weakness

Paresis

Asthenia

Muscular Diseases

Neuromuscular Manifestations

Neurologic Manifestations

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Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

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Autoimmune Diseases of the Nervous System

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Neuromuscular Diseases

RVT-1401 680 mg weekly for 6 weeks + optional open-label extension (RVT-1401, 340 mg every 2 weeks for 6 weeks)

RVT-1401 340 mg weekly for 6 weeks + optional open-label extension (RVT-1401, 340 mg every 2 weeks for 6 weeks)

Placebo for 6 weeks + optional open-label extension (RVT-1401, 340 mg every 2 weeks for 6 weeks)

RVT-1401

Placebo

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.

Randomized, Double-Blind, Placebo-Controlled Study with an Open-Label Extension

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

A Phase 2a, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label Extension of RVT-1401 in Myasthenia Gravis 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.

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 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.

Immunovant Sciences GmbH

Adverse events and Serious adverse events were collected in Safety Analysis Set in Double-Blind Treatment Period and in OLE Analysis Set in Open-Label Extension Period. Safety Analysis Set comprised of all participants who received at least 1 dose of study medication. 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 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. Participants

Double-blind Treatment Period: Placebo

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

Double-blind Treatment Period: RVT-1401 340 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. Participants

Double-blind Treatment Period: RVT-1401 680 mg/Week

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.

Open-label Extension Period: RVT-1401 340 mg Biweekly

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.

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.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Safety Analysis Set (SAF) comprised of all participants who received at least 1 dose of study medication.

Central Study Contact

Any AE

Any SAE

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.

Double-Blind Treatment Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Open-Label Extension Period: RVT-1401 340 mg Biweekly

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.

Open-Label Extension Period: Number of Participants Reporting AEs and SAEs

Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Vital Signs

OLE Analysis Set. Participants were analyzed based on the randomization schedule, regardless of the treatment actually received.

Open-label Extension Period: Number of Participants With Clinically Significant Changes in Vital Signs

Double-blind Treatment Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters

Open-label Extension Period: Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters

Double-Blind Treatment Period: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)

Open-label Extension Period: Number of Participants With Clinically Significant Changes in ECG

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.

Double-blind Treatment Period: Percent Change From Baseline in Levels of Total Immunoglobulin G (IgG)

IgG1

IgG2

IgG3

IgG4

Full Analysis Set. Only those participants with data available at specified time points has been presented.

Double-blind Treatment Period: Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4

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 an additional 3 doses of 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.

Full Analysis Set. Only those participants with data available at definite timepoints has been presented.

Double-Blind Treatment Period: Percent Change From Baseline in Anti-acetylcholine Receptor Immunoglobulin G (Anti-AChR-IgG) at Week 7

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.

Double-Blind Treatment Period: Area Under the Concentration-time Curve From Time 0 to 168 Hours (AUC0-168h) of RVT-1401

Pharmacokinetic Analysis Set. Participants were analyzed based on the randomization schedule, regardless of the treatment actually received.

Open-label Extension Period: AUC0-168h of RVT-1401

Double-Blind Treatment Period: Maximum Concentration (Cmax) of RVT-1401

Open-label Extension Period: Cmax of RVT-1401

Double-Blind Treatment Period: Trough Concentrations (Ctrough) of RVT-1401

Open-label Extension Period: Ctrough of RVT-1401

Week 2, n=6,5,6

Week 3, n=6,5,6

Week 4, n=6,5,5

Week 5, n=6,5,5

Week 6 (Day 36), n=6,5,5

Week 7, n=5,5,5

Full Analysis Set. Only those participants with data available at specified time points has been represented (represented by n=X in the category titles).

Double-blind Treatment Period: Change From Baseline in the Quantitative Myasthenia Gravis Score (QMG) Score

Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the QMG Score From Baseline

Week 2

Week 3

Week 4

Week 5

Week 6 (Day 36)

Week 7

Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Score

Double-Blind Treatment Period: Percentage of Participants With an Improvement/ Response on the MG-ADL Score

Full Analysis Set. Only those participants with data available at specified timepoints has been presented.

Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Composite Score (MGC) Score

Double-Blind Treatment Period: Percentage of Participants With an Improvement on the MGC Score

Double-Blind Treatment Period: Change From Baseline in the Myasthenia Gravis Quality of Life 15 Revised Score (MG-QOL 15r) Score

Double-Blind Treatment Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies

Open-Label Extension Period: Number of Participants Reporting Confirmed Positive Anti-RVT-1401 Antibodies

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.

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.

Spots Global Cancer Trial Database for A Study of RVT-1401 in Myasthenia Gravis (MG) Patients

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