Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy (GO)

Immunovant Sciences GmbH7 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Graves' Ophthalmopathy

Interventions

RVT-1401DRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (4)

UBC/VGH Eye Care Center

Vancouver, British Columbia, Canada

Toronto Retina Institute

North York, Ontario, Canada

University of Ottwa Eye Institute

Ottawa, Ontario, Canada

CIUSSS de I'Est-de-I'lle-de-Montreal, Installation Maisonneuve- Rosemont

Montreal, Quebec, Canada

Outcomes

Primary Outcomes

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.

Time frame: from Baseline up to Week 6

Number of Participants With Clinically Significant Findings Related to Vital Signs

Clinical significance was determined by the investigator.

Time frame: up to Week 18

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.

Time frame: up to Week 18

Number of Participants With Clinically Significant Findings Related to Electrocardiograms (ECGs)

Clinical significance was determined by the investigator.

Time frame: up to Week 18

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.

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: Baseline; Week 7

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.

Time frame: Up to Week 18

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.

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

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.

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

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

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.

Time frame: Week 7