Clinical trial NCT05276063: A Phase 2b, Study of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED)
Official title: A Phase 2b, Randomized, Double-Mask, Placebo-Controlled, Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Thyroid Eye Disease
Graves Orbitopathy
Endocrine System Diseases
Eye Diseases
Thyroid Associated Ophthalmopathy
Graves Ophthalmopathy
Thyroid Diseases
Orbital Diseases
Proptosis
IGF1R
Exophthalmos
Hashimoto
Keywords: Thyroid Associated Ophthalmopathies
Lead sponsor: Sling Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-03-11
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The overall objective is to study the safety, pharmacokinetics and efficacy of linsitinib (a small molecule IGF-1R inhibitor) administered orally twice daily (BID) vs. placebo, at 24 weeks in the treatment of subjects with active, moderate to severe thyroid eye disease (TED).


Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of Graves' Disease and/or autoimmune Hashimoto's thyroiditis associated with active moderate to severe TED with a CAS ≥ 4 (on the 7- item scale) for the most severely affected eye (primary study eye) at Screening and Baseline
* Confirmed active TED (not sight-threatening but has an appreciable impact on daily life, with onset (as determined by patient records) within 12 months prior to the Baseline visit and usually associated with one or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, exophthalmos ≥ 3 mm above normal for race and gender, and/or inconstant or constant diplopia.
* Subjects must be euthyroid with the participant's baseline disease under control or have mild hypo- or hyperthyroidism (defined as free thyroxine \[FT4\] and free triiodothyronine levels \[FT3\] \< 50% above or below the normal limits) at Screening.
* Does not require immediate ophthalmic surgery, radiotherapy to orbits or other ophthalmological intervention at the time of Screening and is not planning for any such treatment during the course of the study.

Exclusion Criteria:

* 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.
* Corneal decompensation unresponsive to medical management.
* Previous orbital irradiation or orbital surgery.
* Any glucocorticoid use (intravenous \[IV\] or oral) with a cumulative dose equivalent to \>= 1g of methylprednisolone or equivalent for the treatment of TED within 3 months of Screening.
* Prior IGF-1R inhibitor therapy for any condition.

Primary outcomes:
measure: Percentage of Subjects who are Proptosis Responders at Week 24
timeFrame: 24 weeks
Secondary outcomes:
measure: Change from Baseline in Proptosis to Week 24 (Study Eye)
timeFrame: 24 weeks
measure: Percentage of Subjects who are Diplopia Responders at Week 24
timeFrame: 24 weeks
measure: Percentage of Subjects who are Overall Responders at Week 24
timeFrame: 24 weeks
measure: Percentage of Subjects who are CAS Categorical Responders at Week 24 (Study Eye)
timeFrame: 24 weeks
measure: Change from Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score to Week 24.
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Thrive Health Research
state: California
city: La Jolla
country: United States
facility: UC San Diego Health
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Palo Alto
country: United States
facility: Byers Eye Institute - Stanford University
state: California
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Miami
country: United States
facility: Center for Excellence in Eye Care
state: Florida
city: Sarasota
country: United States
facility: Sarasota Retina Institute
state: Florida
city: Chicago
country: United States
facility: Chicago Oculofacial Plastic Surgery
state: Illinois
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Boston
country: United States
facility: Mass Eye and Ear
state: Massachusetts
city: Ann Arbor
country: United States
facility: Kellogg Eye Center
state: Michigan
city: Livonia
country: United States
facility: Kahana Oculoplastic & Orbital Surgery
state: Michigan
city: Creve Coeur
country: United States
facility: Washington University in St. Louis/Barnes Jewish Hospital
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health Eye Center
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Bellaire
country: United States
facility: Neuro-Eye Clinical Trials, Inc.
state: Texas
city: Salt Lake City
country: United States
facility: Eyelid Center of Utah
state: Utah
city: Morgantown
country: United States
facility: West Virginia University Eye Institute
state: West Virginia
city: Vancouver
country: Canada
facility: Vancouver Coastal Health Eye Care Center
state: British Columbia
city: North York
country: Canada
facility: Toronto Retina Institute
city: Milan
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Endocrinology Pawilione Zonda
city: Pisa
country: Italy
facility: AOU Pisana
city: Pisa
country: Italy
facility: University of Pisa
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Madrid
country: Spain
facility: Hospital La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Camberley
country: United Kingdom
facility: Frimley Health Foundation Trust
city: Cardiff
country: United Kingdom
facility: Cardiff University
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NIHR Clinical Research Facility
Study officials:
References: