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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03922321
Other study ID # RVT-1401-1002
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date April 22, 2019
Est. completion date May 21, 2020

Study information

Verified date December 2021
Source Immunovant Sciences GmbH
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study was to evaluate safety, tolerability, and pharmacodynamic parameters of RVT-1401 in graves' ophthalmopathy (GO) patients.


Recruitment information / eligibility

Status Completed
Enrollment 7
Est. completion date May 21, 2020
Est. primary completion date February 29, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Male or female = 18 years of age. 2. 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). 3. Onset of active GO within 9 months of screening. 4. 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. 5. Other, more specific inclusion criteria are defined in the protocol Exclusion Criteria: 1. 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. 2. Use of rituximab, tocilizumab, or any monoclonal antibody for immunomodulation within the past 9 months prior to Baseline. 3. Total IgG level < 6g/L at Screening. 4. Absolute neutrophil count <1500 cells/mm3 at Screening. 5. 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. 6. Previous orbital irradiation or surgery for GO. 7. Other, more specific exclusion criteria are defined in the protocol

Study Design


Intervention

Drug:
RVT-1401
RVT-1401 is a fully human anti-neonatal Fc receptor (FcRn) monoclonal antibody.

Locations

Country Name City State
Canada CIUSSS de I'Est-de-I'lle-de-Montreal, Installation Maisonneuve- Rosemont Montreal Quebec
Canada Toronto Retina Institute North York Ontario
Canada University of Ottwa Eye Institute Ottawa Ontario
Canada UBC/VGH Eye Care Center Vancouver British Columbia

Sponsors (1)

Lead Sponsor Collaborator
Immunovant Sciences GmbH

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. from Baseline up to Week 6
Primary Number of Participants With Clinically Significant Findings Related to Vital Signs Clinical significance was determined by the investigator. up to Week 18
Primary 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. up to Week 18
Primary Number of Participants With Clinically Significant Findings Related to Electrocardiograms (ECGs) Clinical significance was determined by the investigator. up to Week 18
Primary 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. Baseline; Week 7; Week 6 and 7 combined
Primary 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. Baseline; Week 7
Secondary 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. Baseline; Week 7
Secondary 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. Up to Week 18
Secondary 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. 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
Secondary 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. 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
Secondary Serum Concentration at the End of the Dosing Interval (Ctrough) of RVT-1401 Week 2, Week 3, Week 4, Week 5, Week 6 Day 36, and Week 7
Secondary 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. Week 7
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