ASCEND GO-2: Study of RVT-1401 for the Treatment of Participants With Active, Moderate to Severe Graves' Ophthalmopathy ( GO )

NCT03938545 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: RVT-1401-2001
• Study Type: interventional
• Target: 65
• Locations: 5 countries
• Sites: 25

Brief Summary

The purpose of the current study is to assess the efficacy and safety/tolerability of three dose regimens of RVT-1401 in the treatment of active, moderate to severe GO participants. In addition, the study is designed to characterize the effect of RVT-1401 exposure on reduction in anti-TSHR IgG

Conditions

Graves' Ophthalmopathy (GO)

Keywords

IMVT-1401; Graves' Orbitopathy; Thyroid Eye Disease

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Proptosis Response at Week 13

  Proptosis was assessed using an exophthalmometer. A proptosis response was defined as having at least a 2 millimeter (mm) reduction in study eye proptosis without a deterioration (at least a 2 mm increase) in the fellow eye at the same visit. The study eye was defined as the most severely affected eye at the baseline visit.

  Baseline; Week 13

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)

  AEs - any untoward medical occurrences in a participant, temporally associated with use of a medicinal product, whether or not considered related to the product. Clinically significant changes determined by the Investigator such as vital signs, ECGs, and clinical laboratory values were also reported as AEs. TEAE is defined as an AE that starts on or after the first dose of the study drug and before 30 days after the last dose of the study drug. SAEs were defined as any untoward medical occurrences that: resulted in death; were life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; were congenital anomaly/birth defects; were important medical events that may have jeopardized the participant or may have required medical or surgical intervention; invasive or malignant cancers; and development of drug dependency or drug abuse.

  From Baseline up to Week 20

Secondary Outcomes (3)

• Least Square Mean Percent Change From Baseline in Binding Anti-thyroid-stimulating Hormone Receptor (TSHR) Antibody Levels to Week 13

  Baseline and Week 13

• Least Square Mean Percent Change From Baseline in Total IgG Levels

  Baseline and Week 13

• Least Square Mean Percent Change From Baseline in IgG Subclasses 1, 2, 3 and 4

  Baseline and Week 13

Study Arms (4)

Regimen A-RVT-1401

EXPERIMENTAL

Regimen A= RVT-1401 680 mg weekly for 12 weeks

Drug: RVT-1401 (Administered via subcutaneous injection)

Regimen B-RVT-1401

EXPERIMENTAL

Regimen B= RVT-1401 340 mg weekly for 12 weeks

Drug: RVT-1401 (Administered via subcutaneous injection)

Regimen C-RVT-1401

EXPERIMENTAL

Regimen C= RVT-1401 255 mg weekly for 12 weeks

Drug: RVT-1401 (Administered via subcutaneous injection)

Placebo

PLACEBO COMPARATOR

for 12 weeks

Other: Placebo (Administered via subcutaneous injection)

Interventions

RVT-1401 (Administered via subcutaneous injection) DRUG

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

Regimen A-RVT-1401; Regimen B-RVT-1401; Regimen C-RVT-1401

Placebo (Administered via subcutaneous injection) OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥18 years of age.
• Clinical diagnosis of Graves' disease with hyperthyroidism associated with active, moderate to severe Graves' Ophthalmopathy (GO) with a Clinical Activity Score (CAS) ≥4 for the most severely affected eye at Screening and Baseline (on the 7-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 millimeters (mm), moderate or severe soft tissue involvement, proptosis ≥3 mm above normal for race and gender, and/or inconstant or constant diplopia.

You may not qualify if:

• Use of any steroid (intravenous, oral, steroid eye drops) for the treatment of GO or other conditions within 3 weeks prior to Screening. Steroids cannot be initiated during the trial. Exceptions include topical and inhaled steroids which are allowed.
• Use of rituximab, tocilizumab, or any monoclonal antibody for immunomodulation within the past 9 months prior to Baseline.
• Total IgG level \<6 grams per liter (g/L) at Screening.
• Absolute neutrophil count \<1500 cells per meter squared (cells/mm\^3) 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.

Sponsors & Collaborators

• Immunovant Sciences GmbH: lead

Study Sites (25)

Multispecialty Aesthetic Clinical Research Organziation (MACRO)

Beverly Hills, California, 90212, United States

Location

Doheny Eye Center UCLA

Pasadena, California, 91105, United States

Location

University of Miami Miller School of Medicine Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

University of Iowa Hospitals & Clinics - Eye Clinic

Iowa City, Iowa, 52242, United States

Location

University of Michigan - Kellogg Eye Center

Ann Arbor, Michigan, 48105, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine - Center for Advanced Medicine (CAM) - Eye Center

St Louis, Missouri, 63146, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Oregon Health & Science University (OHSU) - Casey Eye Institute (CEI)-Marquam Hill

Portland, Oregon, 97239, United States

Location

Eye Wellness Center

Houston, Texas, 77005, United States

Location

Eyelid Center of Utah

Salt Lake City, Utah, 84102, United States

Location

West Virginia University Eye Institute

Morgantown, West Virginia, 26506, United States

Location

University of British Columbia

Vancouver, British Columbia, V5Z-1M9, Canada

Location

Toronto Retina Institute

North York, Ontario, M3C 0G9, Canada

Location

University of Ottawa Eye Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Ophthalmology University Center- Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Universitat Duisburg-Essen

Duisburg, 47057, Germany

Location

Orbitazentrum Frankfurt

Frankfurt am Main, 60318, Germany

Location

Universitätsmedizin Mainz

Mainz, 55131, Germany

Location

ARNAS Garibaldi, Presidio di Nesima

Palermo, Catania, 95122, Italy

Location

Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Unità Operativa di Endocrinologia 2, Azienda Ospedaliero-Universitaria Pisana

Pisa, 56124, Italy

Location

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Centro de Oftalmologia Barraquer

Barcelona, 08021, Spain

Location

University Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

MeSH Terms

Conditions

Graves Ophthalmopathy

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

The study was terminated early due to a safety finding (hypercholesterolemia).

Results Point of Contact

• Title: Central Study Contact
• Organization: Immunovant, Inc

clinicaltrials@immunovant.com

1-800-797-0414

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2019
• First Posted: May 6, 2019
• Study Start: July 23, 2019
• Primary Completion: February 2, 2021
• Study Completion: April 15, 2021
• Last Updated: September 22, 2022
• Results First Posted: September 22, 2022

Record last verified: 2022-08

Locations

US (12); CA (4); ES (3); IT (3); DE (3)