Back to resultsStudy of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy (GO)
Primary Purpose
Graves' Ophthalmopathy
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
RVT-1401
Sponsored by
About this trial
This is an interventional treatment trial for Graves' Ophthalmopathy focused on measuring IMVT-1401, Graves' Orbitopathy, Thyroid Eye Disease
Eligibility Criteria
Inclusion Criteria:
- Male or female ≥ 18 years of age.
- Clinical diagnosis of Graves' disease with hyperthyroidism associated with active, moderate to severe GO with a Clinical Activity Score (CAS) ≥ 4 for the most severely affected eye at Screening (on the 7-item scale) and Baseline (on the 10-item scale).
- Onset of active GO within 9 months of screening.
- Moderate-to-severe active GO (not sight-threatening but has an appreciable impact on daily life), usually associated with one or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, proptosis ≥ 3 mm above normal for race and gender, and/or inconstant or constant diplopia.
- Other, more specific inclusion criteria are defined in the protocol
Exclusion Criteria:
- Use of any steroid (intravenous [IV] or oral) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone for the treatment of GO within 3 weeks prior to Screening.
- Use of rituximab, tocilizumab, or any monoclonal antibody for immunomodulation within the past 9 months prior to Baseline.
- Total IgG level < 6g/L at Screening.
- Absolute neutrophil count <1500 cells/mm3 at Screening.
- Participants with decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months at Screening.
- Previous orbital irradiation or surgery for GO.
- Other, more specific exclusion criteria are defined in the protocol
Sites / Locations
- UBC/VGH Eye Care Center
- Toronto Retina Institute
- University of Ottwa Eye Institute
- CIUSSS de I'Est-de-I'lle-de-Montreal, Installation Maisonneuve- Rosemont
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
RVT-1401
Arm Description
RVT-1401 680 milligrams (mg) weekly for two weeks followed by 340 mg weekly for four weeks, administered subcutaneously
Outcomes
Primary Outcome Measures
Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Serious AE (SAE), Treatment-related Adverse Event (AE), and Death During the 6-week Treatment Period
AEs were defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as AEs that either started on or after the date of the first dose of study drug and on or before the date of the last dose of study drug + 42 days, or had no recorded start date and the stop date was in between the date of the first dose and the last dose of study drug + 42 days. 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.
Number of Participants With Clinically Significant Findings Related to Vital Signs
Clinical significance was determined by the investigator.
Number of Participants With a Change From Normal Physical Examination Findings at Baseline to Abnormal Physical Examination Findings at the End of the Study
Abnormality was determined by the investigator.
Number of Participants With Clinically Significant Findings Related to Electrocardiograms (ECGs)
Clinical significance was determined by the investigator.
Percent Change From Baseline in Total Immunoglobulin G (IgG), IgG1, IgG2, IgG3, and IgG4 Levels
The serum levels of total IgG and IgG subclasses (1-4) were determined. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7, Week 6 and 7 combined) minus the Baseline value, divided by the Baseline value x 100. A negative percent change from Baseline represents clinical improvement.
Mean Change From Baseline in Levels of Anti-thyroid-stimulating Hormone Receptor (Anti-TSHR) Antibodies at Week 7
The serum levels of anti-TSHR antibodies were determined. Change from Baseline was calculated as the Week 7 value minus the Baseline value. A negative change from Baseline represents clinical improvement.
Secondary Outcome Measures
Mean Change From Baseline in Proptosis in the Study Eye and Non-study Eye at Week 7
The study eye was defined as the most severely affected eye at the Baseline visit. In the event that both eyes were affected the same, the right eye was deemed as the study eye. Participants who did not achieve a proptosis response were censored at the date of their last proptosis measurement that occurred in both eyes. Change from Baseline was calculated as the Week 7 value minus the Baseline value. A negative change from Baseline represents clinical improvement.
Number of Participants With an Overall Proptosis Response
Proptosis responders were defined as participants with a ≥2 mm reduction in study eye without deterioration (≥2 mm increase) in the fellow eye. Participants who did not achieve a proptosis response were censored at the date of their last proptosis measurement that occurred in both eyes.
Area Under the Concentration-time Curve From Time 0 to 168 Hours (AUC0-168h) of RVT-1401
Pharmacokinetic (PK) parameters were not estimated because the sparse PK sampling schedule did not allow for accurate estimates of these parameters.
Maximum Concentration (Cmax) of RVT-1401
PK parameters were not estimated because the sparse PK sampling schedule did not allow for accurate estimates of these parameters.
Serum Concentration at the End of the Dosing Interval (Ctrough) of RVT-1401
Number of Participants With Anti-RVT-1401 Antibody and Confirmed Anti-RVT-1401 Antibody at Week 7
The serum levels of anti-RVT-1401 antibodies were determined. In the initial analysis the samples with responses equal to or above the plate-specific cut-point were identified as potentially positive while those below the cut-point were considered negative. These potentially positive samples were reanalyzed in confirmatory assay. Samples with percent inhibition greater than or equal to the confirmatory cut-point were considered confirmed positive and those below were considered negative.
Full Information
NCT ID
NCT03922321
First Posted
April 17, 2019
Last Updated
December 24, 2021
Sponsor
Immunovant Sciences GmbH
1. Study Identification
Unique Protocol Identification Number
NCT03922321
Brief Title
Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy (GO)
Official Title
A Phase 2a, Multicenter, Open-Label Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
April 22, 2019 (Actual)
Primary Completion Date
February 29, 2020 (Actual)
Study Completion Date
May 21, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Immunovant Sciences GmbH
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
Brief Summary
The purpose of this study was to evaluate safety, tolerability, and pharmacodynamic parameters of RVT-1401 in graves' ophthalmopathy (GO) patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graves' Ophthalmopathy
Keywords
IMVT-1401, Graves' Orbitopathy, Thyroid Eye Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open label study
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RVT-1401
Arm Type
Experimental
Arm Description
RVT-1401 680 milligrams (mg) weekly for two weeks followed by 340 mg weekly for four weeks, administered subcutaneously
Intervention Type
Drug
Intervention Name(s)
RVT-1401
Intervention Description
RVT-1401 is a fully human anti-neonatal Fc receptor (FcRn) monoclonal antibody.
Primary Outcome Measure Information:
Title
Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Serious AE (SAE), Treatment-related Adverse Event (AE), and Death During the 6-week Treatment Period
Description
AEs were defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as AEs that either started on or after the date of the first dose of study drug and on or before the date of the last dose of study drug + 42 days, or had no recorded start date and the stop date was in between the date of the first dose and the last dose of study drug + 42 days. 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
from Baseline up to Week 6
Title
Number of Participants With Clinically Significant Findings Related to Vital Signs
Description
Clinical significance was determined by the investigator.
Time Frame
up to Week 18
Title
Number of Participants With a Change From Normal Physical Examination Findings at Baseline to Abnormal Physical Examination Findings at the End of the Study
Description
Abnormality was determined by the investigator.
Time Frame
up to Week 18
Title
Number of Participants With Clinically Significant Findings Related to Electrocardiograms (ECGs)
Description
Clinical significance was determined by the investigator.
Time Frame
up to Week 18
Title
Percent Change From Baseline in Total Immunoglobulin G (IgG), IgG1, IgG2, IgG3, and IgG4 Levels
Description
The serum levels of total IgG and IgG subclasses (1-4) were determined. Percent change from Baseline was calculated as the mean value at the specified time frame (Week 7, Week 6 and 7 combined) minus the Baseline value, divided by the Baseline value x 100. A negative percent change from Baseline represents clinical improvement.
Time Frame
Baseline; Week 7; Week 6 and 7 combined
Title
Mean Change From Baseline in Levels of Anti-thyroid-stimulating Hormone Receptor (Anti-TSHR) Antibodies at Week 7
Description
The serum levels of anti-TSHR antibodies were determined. Change from Baseline was calculated as the Week 7 value minus the Baseline value. A negative change from Baseline represents clinical improvement.
Time Frame
Baseline; Week 7
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in Proptosis in the Study Eye and Non-study Eye at Week 7
Description
The study eye was defined as the most severely affected eye at the Baseline visit. In the event that both eyes were affected the same, the right eye was deemed as the study eye. Participants who did not achieve a proptosis response were censored at the date of their last proptosis measurement that occurred in both eyes. Change from Baseline was calculated as the Week 7 value minus the Baseline value. A negative change from Baseline represents clinical improvement.
Time Frame
Baseline; Week 7
Title
Number of Participants With an Overall Proptosis Response
Description
Proptosis responders were defined as participants with a ≥2 mm reduction in study eye without deterioration (≥2 mm increase) in the fellow eye. Participants who did not achieve a proptosis response were censored at the date of their last proptosis measurement that occurred in both eyes.
Time Frame
Up to Week 18
Title
Area Under the Concentration-time Curve From Time 0 to 168 Hours (AUC0-168h) of RVT-1401
Description
Pharmacokinetic (PK) 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
Title
Maximum Concentration (Cmax) of RVT-1401
Description
PK 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
Title
Serum Concentration at the End of the Dosing Interval (Ctrough) of RVT-1401
Time Frame
Week 2, Week 3, Week 4, Week 5, Week 6 Day 36, and Week 7
Title
Number of Participants With Anti-RVT-1401 Antibody and Confirmed Anti-RVT-1401 Antibody at Week 7
Description
The serum levels of anti-RVT-1401 antibodies were determined. In the initial analysis the samples with responses equal to or above the plate-specific cut-point were identified as potentially positive while those below the cut-point were considered negative. These potentially positive samples were reanalyzed in confirmatory assay. Samples with percent inhibition greater than or equal to the confirmatory cut-point were considered confirmed positive and those below were considered negative.
Time Frame
Week 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female ≥ 18 years of age.
Clinical diagnosis of Graves' disease with hyperthyroidism associated with active, moderate to severe GO with a Clinical Activity Score (CAS) ≥ 4 for the most severely affected eye at Screening (on the 7-item scale) and Baseline (on the 10-item scale).
Onset of active GO within 9 months of screening.
Moderate-to-severe active GO (not sight-threatening but has an appreciable impact on daily life), usually associated with one or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, proptosis ≥ 3 mm above normal for race and gender, and/or inconstant or constant diplopia.
Other, more specific inclusion criteria are defined in the protocol
Exclusion Criteria:
Use of any steroid (intravenous [IV] or oral) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone for the treatment of GO within 3 weeks prior to Screening.
Use of rituximab, tocilizumab, or any monoclonal antibody for immunomodulation within the past 9 months prior to Baseline.
Total IgG level < 6g/L at Screening.
Absolute neutrophil count <1500 cells/mm3 at Screening.
Participants with decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months at Screening.
Previous orbital irradiation or surgery for GO.
Other, more specific exclusion criteria are defined in the protocol
Facility Information:
Facility Name
UBC/VGH Eye Care Center
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 3N9
Country
Canada
Facility Name
Toronto Retina Institute
City
North York
State/Province
Ontario
ZIP/Postal Code
M3C 0G9
Country
Canada
Facility Name
University of Ottwa Eye Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
CIUSSS de I'Est-de-I'lle-de-Montreal, Installation Maisonneuve- Rosemont
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy (GO)
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