Graves' OphthalmopathyPhase 2NCT03922321

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

A Phase 2 study testing RVT-1401 in people with Graves' Ophthalmopathy, run by Immunovant Sciences GmbH at 4 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Graves' Ophthalmopathy
What is being tested?: RVT-1401
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 4 sitesCanada
Study dates: 22 Apr 2019to 21 May 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

4 sites in 1 country.

Canada4 sites

CIUSSS de I'Est-de-I'lle-de-Montreal, Installation Maisonneuve- Rosemont
Montreal, Quebec, H1T 2M4
Toronto Retina Institute
North York, Ontario, M3C 0G9
University of Ottwa Eye Institute
Ottawa, Ontario, K1H 8L6
UBC/VGH Eye Care Center
Vancouver, British Columbia, V5Z 3N9

Other trials in Canada

About this study

Official title: A Phase 2a, Multicenter, Open-Label Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy

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

Conditions: Graves' Ophthalmopathy
Being tested: RVT-1401
Keywords: IMVT-1401, Graves' Orbitopathy, Thyroid Eye Disease
Medical subject headings: Graves Ophthalmopathy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03922321
Study group	Role	What they receive
RVT-1401	Experimental	RVT-1401 680 milligrams (mg) weekly for two weeks followed by 340 mg weekly for four weeks, administered subcutaneously Receives: Drug: RVT-1401

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: from Baseline up to Week 6
Number of Participants With Clinically Significant Findings Related to Vital Signs
Clinical significance was determined by the investigator.
Measured: 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.
Measured: up to Week 18
Number of Participants With Clinically Significant Findings Related to Electrocardiograms (ECGs)
Clinical significance was determined by the investigator.
Measured: 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.
Measured: 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.
Measured: Baseline; Week 7

Secondary outcomes (6)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: Week 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Apr 201921 May 2020

First posted19 Apr 2019
Study start22 Apr 2019
Primary completion29 Feb 2020
Study completion21 May 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Graves' OphthalmopathyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Open label study
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03922321
Sponsor's protocol ID: RVT-1401-1002
Status last verified: Dec 2021
First submitted: 17 Apr 2019
Last updated: 24 Jan 2022
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Impact of Restrictive Diets on Inflammation and Quality of Life in Autoimmune Thyroiditis
Thyroid Autoimmune Disease, Hashimoto's Thyroiditis
RecruitingPhase 3
A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease
Graves' Disease, Graves Disease
RecruitingPhase 3
A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease.
Graves Disease
Active, not recruitingPhase 4
Hydroxychloroquine in Mild Graves' Orbitopathy
Graves Ophthalmopathy
RecruitingPhase 2
A Study to Assess the Efficacy, Safety, and Tolerability of IMVT-1402 as Treatment for Adult Participants With Graves' Disease
Graves' Disease

All Graves' Ophthalmopathy trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2a, Multicenter, Open-Label Study of RVT-1401 for the Treatment of Patients With Moderate to Severe Active Graves' Ophthalmopathy
ClinicalTrials.gov ID: NCT03922321
Acronym / sponsor ID: RVT-1401-1002
Conditions: Graves' Ophthalmopathy
Keywords: IMVT-1401, Graves' Orbitopathy, Thyroid Eye Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 7 participants (actual)
Lead sponsor: Immunovant Sciences GmbHIndustry (pharma, biotech, devices)
Study start: 22 Apr 2019 (actual)
Primary completion: 29 Feb 2020 (actual)
Study completion: 21 May 2020 (actual)
First posted: 19 Apr 2019 (actual)
Results: Posted 24 Jan 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Open label study

Arm	Type	Receives
RVT-1401	Experimental	Drug: RVT-1401RVT-1401 680 milligrams (mg) weekly for two weeks followed by 340 mg weekly for four weeks, administered subcutaneously

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

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

Primary outcome

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
Time frame: from Baseline up to Week 6
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
Time frame: up to Week 18
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
Time frame: up to Week 18
Abnormality was determined by the investigator.
Number of Participants With Clinically Significant Findings Related to Electrocardiograms (ECGs)
Time frame: up to Week 18
Clinical significance was determined by the investigator.
Percent Change From Baseline in Total Immunoglobulin G (IgG), IgG1, IgG2, IgG3, and IgG4 Levels
Time frame: Baseline; Week 7; Week 6 and 7 combined
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
Time frame: Baseline; 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.

6 secondary outcomes

Mean Change From Baseline in Proptosis in the Study Eye and Non-study Eye at Week 7
Time frame: Baseline; Week 7
Number of Participants With an Overall Proptosis Response
Time frame: Up to Week 18
Area Under the Concentration-time Curve From Time 0 to 168 Hours (AUC0-168h) of RVT-1401
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
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
Time frame: Week 7

Results and safety

Results posted to the registry on 24 Jan 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
RVT-1401	7	5

Primary outcome: 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

Time frame: from Baseline up to Week 6. Count of participants. Unit: Participants

Measure	RVT-1401 n = 7
TEAEs	7
SAEs	0
Treatment-related AEs	6
Deaths	0

Population analysed: Safety Population: all participants who received at least one dose of study treatment

Primary outcome: Number of Participants With Clinically Significant Findings Related to Vital Signs

Time frame: up to Week 18. Count of participants. Unit: Participants

Measure	RVT-1401 n = 7
Value	0

Population analysed: Safety Population

Primary outcome: Number of Participants With a Change From Normal Physical Examination Findings at Baseline to Abnormal Physical Examination Findings at the End of the Study

Time frame: up to Week 18. Count of participants. Unit: Participants

Measure	RVT-1401 n = 7
Value	0

Population analysed: Safety Population

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

Time frame: up to Week 18. Count of participants. Unit: Participants

Measure	RVT-1401 n = 7
Value	0

Population analysed: Safety Population

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: from Baseline up to Week 18. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
RVT-1401	0 of 7 (0%)	7 of 7 (100%)	0 of 7

Limitations and caveats (from the sponsor): The PK parameters of AUC0-168h and Cmax were not estimated because of sparse PK sampling schedule.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Graves' Ophthalmopathy

Not yet recruiting
Impact of Restrictive Diets on Inflammation and Quality of Life in Autoimmune Thyroiditis
Thyroid Autoimmune Disease, Hashimoto's Thyroiditis
RecruitingPhase 3
A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease
Graves' Disease, Graves Disease
RecruitingPhase 3
A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease.
Graves Disease
Active, not recruitingPhase 4
Hydroxychloroquine in Mild Graves' Orbitopathy
Graves Ophthalmopathy
RecruitingPhase 2
A Study to Assess the Efficacy, Safety, and Tolerability of IMVT-1402 as Treatment for Adult Participants With Graves' Disease
Graves' Disease

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RVT-1401 in people with Graves' Ophthalmopathy, run by Immunovant Sciences GmbH at 4 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: from Baseline up to Week 6). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03922321.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2022.