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The purpose of this study was to evaluate safety, tolerability, and pharmacodynamic parameters of RVT-1401 in graves' ophthalmopathy (GO) patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RVT-1401 | Experimental | RVT-1401 680 milligrams (mg) weekly for two weeks followed by 340 mg weekly for four weeks, administered subcutaneously |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RVT-1401 | Drug | RVT-1401 is a fully human anti-neonatal Fc receptor (FcRn) monoclonal antibody. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Number of Participants With Clinically Significant Findings Related to Vital Signs | Clinical significance was determined by the investigator. | 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. | up to Week 18 |
| Number of Participants With Clinically Significant Findings Related to Electrocardiograms (ECGs) | Clinical significance was determined by the investigator. | up to Week 18 |
| Percent Change From Baseline in Total Immunoglobulin G (IgG), IgG1, IgG2, IgG3, and IgG4 Levels |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UBC/VGH Eye Care Center | Vancouver | British Columbia | V5Z 3N9 | Canada | ||
| Toronto Retina Institute |
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A total of 8 participants were screened for the study. Only 7 participants were randomized; 1 participant failed to meet the screening criteria.
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| ID | Title | Description |
|---|---|---|
| FG000 | RVT-1401 | Participants received a RVT-1401 680 milligram (mg) subcutaneous (SC) injection weekly for 2 weeks, followed by a 340 mg SC injection weekly for 4 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | RVT-1401 | Participants received a RVT-1401 680 milligram (mg) subcutaneous (SC) injection weekly for 2 weeks, followed by a 340 mg SC injection weekly for 4 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Safety Population: all participants who received at least one dose of study treatment |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Safety Population: all participants who received at least one dose of study treatment | Posted | Count of Participants | Participants | from Baseline up to Week 6 |
from Baseline up to Week 18
Treatment-emergent adverse events (TEAEs), 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, were collected in participants in the Safety Population (comprised of all participants who received at least 1 dose of study treatment) during the treatment period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | RVT-1401 | Participants received a RVT-1401 680 milligram (mg) subcutaneous (SC) injection weekly for 2 weeks, followed by a 340 mg SC injection weekly for 4 weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDra 21.1 | Systematic Assessment |
The PK parameters of AUC0-168h and Cmax were not estimated because of sparse PK sampling schedule.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Central Study Contact | Immunovant, Inc | 1-800-797-0414 | clinicaltrials@immunovant.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 7, 2019 | Sep 21, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 16, 2019 | Sep 21, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D049970 | Graves Ophthalmopathy |
| ID | Term |
|---|---|
| D015785 | Eye Diseases, Hereditary |
| D005128 | Eye Diseases |
| D006111 | Graves Disease |
| D005094 | Exophthalmos |
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Open label study
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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 |
| 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 |
| 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. | 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. | 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. | 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 | 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. | Week 7 |
| North York |
| Ontario |
| M3C 0G9 |
| Canada |
| University of Ottwa Eye Institute | Ottawa | Ontario | K1H 8L6 | Canada |
| CIUSSS de I'Est-de-I'lle-de-Montreal, Installation Maisonneuve- Rosemont | Montreal | Quebec | H1T 2M4 | Canada |
| Mean |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | Safety Population: all participants who received at least one dose of study treatment | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Safety Population: all participants who received at least one dose of study treatment | Count of Participants | Participants | No |
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| Race (NIH/OMB) | Safety Population: all participants who received at least one dose of study treatment | Count of Participants | Participants | No |
|
| Total Immunoglobulin G (IgG), IgG1, IgG2, IgG3, and IgG4 Levels | The serum levels of total IgG and IgG subclasses (1-4) were determined. | Pharmacodynamic (PD) Population: all participants who had a Baseline PD measurement and at least 1 post-Baseline PD measurement and received at least 1 dose of study drug | Mean | Standard Deviation | grams per liter (g/L) |
|
| ID | Title | Description |
|---|---|---|
| OG000 | RVT-1401 | Participants received a RVT-1401 680 milligram (mg) subcutaneous (SC) injection weekly for 2 weeks, followed by a 340 mg SC injection weekly for 4 weeks. |
|
|
| Primary | Number of Participants With Clinically Significant Findings Related to Vital Signs | Clinical significance was determined by the investigator. | Safety Population | Posted | Count of Participants | Participants | 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. | Safety Population | Posted | Count of Participants | Participants | up to Week 18 |
|
|
|
| Primary | Number of Participants With Clinically Significant Findings Related to Electrocardiograms (ECGs) | Clinical significance was determined by the investigator. | Safety Population | Posted | Count of Participants | Participants | 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. | Pharmacodynamic (PD) Population: all participants who had a Baseline PD measurement and at least 1 post-Baseline PD measurement and received at least 1 dose of study drug. Only participants with available data were analyzed. | Posted | Mean | Standard Deviation | Percent change | 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. | PD Population. Only participants with available data were analyzed. | Posted | Mean | Standard Deviation | international units/milliliter (IU/mL) | 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. | PD Population. Only participants with available data were analyzed. | Posted | Mean | Standard Deviation | millimeter (mm) | 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. | PD Population | Posted | Count of Participants | Participants | 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. | PK Population: all participants who received at least one dose of study drug and had at least 1 post-dose PK sample assayed for RVT-1401. Only 2 non-Ctrough time point samples were collected after the first dose (on Day 3 and Day 5) and last dose (on Day 38 and Day 40). As a result, having 2 sparse time point samples did not allow to accurately estimate AUC0-168h parameter. | Posted | 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. | PK Population. PK parameters were not estimated because the sparse PK sampling schedule did not allow for accurate estimates of these parameters. Only 2 non-Ctrough time point samples were collected after the first dose (on Day 3 and Day 5) and last dose (on Day 38 and Day 40). As a result, having 2 sparse time point samples did not allow to accurately estimate Cmax parameter. | Posted | 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 |
|
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| Secondary | Serum Concentration at the End of the Dosing Interval (Ctrough) of RVT-1401 | PK Population. Participants with evaluable data were included for the analysis. | Posted | Mean | Standard Deviation | mg/L | Week 2, Week 3, Week 4, Week 5, Week 6 Day 36, and Week 7 |
|
|
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| 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. | Safety Population | Posted | Count of Participants | Participants | Week 7 |
|
|
|
| 0 |
| 7 |
| 0 |
| 7 |
| 7 |
| 7 |
| Lacrimation increased | Eye disorders | MedDra 21.1 | Systematic Assessment |
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| Eye swelling | Eye disorders | MedDra 21.1 | Systematic Assessment |
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| Ocular hyperaemia | Eye disorders | MedDra 21.1 | Systematic Assessment |
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| Swelling of eyelid | Eye disorders | MedDra 21.1 | Systematic Assessment |
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| Keratopathy | Eye disorders | MedDra 21.1 | Systematic Assessment |
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| Eye pain | Eye disorders | MedDra 21.1 | Systematic Assessment |
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| Eye irritation | Eye disorders | MedDra 21.1 | Systematic Assessment |
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| Superior limbic keratoconjunctivitis | Eye disorders | MedDra 21.1 | Systematic Assessment |
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| Diplopia | Eye disorders | MedDra 21.1 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDra 21.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDra 21.1 | Systematic Assessment |
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| Weight increased | Investigations | MedDra 21.1 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDra 21.1 | Systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDra 21.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDra 21.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDra 21.1 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDra 21.1 | Systematic Assessment |
|
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| D009916 |
| Orbital Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006042 | Goiter |
| D013959 | Thyroid Diseases |
| D004700 | Endocrine System Diseases |
| D006980 | Hyperthyroidism |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| IgG1 (Week 7) |
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| IgG2 (Week 7) |
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| IgG3 (Week 7) |
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| IgG4 (Week 7) |
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| Baseline, non-study eye |
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| Change from Baseline to Week 7, non-study eye |
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| Title | Measurements |
|---|---|
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| Week 4 |
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| Week 5 |
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| Week 6 Day 36 |
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| Week 7 |
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| Confirmed analysis: negative anti-RVT-1401 antibody |
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