Thyroid Eye DiseasePhase 2/3LIDSNCT05276063
A Phase 2b, Study of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED)
A Phase 2/3 study testing Linsitinib in people with Thyroid Eye Disease and Graves Orbitopathy, run by Sling Therapeutics, Inc. at 30 sites in 5 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thyroid Eye Disease, Graves Orbitopathy, Endocrine System Diseases
- What is being tested?
- Linsitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 30 sitesin 5 countries
- Study dates
- 1 Jul 2022to 26 Sep 2025
- Phase
- Phase 2/3
- 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
- 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.
Who cannot join
- 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.
Trial locations and contacts
30 sites in 5 countries.
30 sites in 5 countries
United States19 sites
Kellogg Eye Center
Ann Arbor, Michigan, 48105
Neuro-Eye Clinical Trials, Inc.
Bellaire, Texas, 77401
Thrive Health Research
Beverly Hills, California, 90210
Mass Eye and Ear
Boston, Massachusetts, 02114
Chicago Oculofacial Plastic Surgery
Chicago, Illinois, 60614
Washington University in St. Louis/Barnes Jewish Hospital
Creve Coeur, Missouri, 63141
UC San Diego Health
La Jolla, California, 92093
Kahana Oculoplastic & Orbital Surgery
Livonia, Michigan, 48152
UCLA
Los Angeles, California, 90095
Bascom Palmer Eye Institute
Miami, Florida, 33136
Center for Excellence in Eye Care
Miami, Florida, 33176
West Virginia University Eye Institute
Morgantown, West Virginia, 26506
Columbia University
New York, New York, 10032
Byers Eye Institute - Stanford University
Palo Alto, California, 94303
Oregon Health and Science University
Portland, Oregon, 97239
Eyelid Center of Utah
Salt Lake City, Utah, 84102
Sarasota Retina Institute
Sarasota, Florida, 34239
Wolfe Eye Clinic
West Des Moines, Iowa, 50266
Wake Forest Baptist Health Eye Center
Winston-Salem, North Carolina, 27157
Italy3 sites
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Endocrinology Pawilione Zonda
Milan
AOU Pisana
Pisa
University of Pisa
Pisa
Spain3 sites
Hospital Universitari de Bellvitge
Barcelona, 08907
Hospital La Princesa
Madrid, 28006
Hospital Universitario Ramon y Cajal
Madrid, 28034
United Kingdom3 sites
Frimley Health Foundation Trust
Camberley, GU16 7UJ
Cardiff University
Cardiff, CF14 4XN
Moorfields Eye Hospital NIHR Clinical Research Facility
London, EC1V 2PD
Canada2 sites
Toronto Retina Institute
North York, M3C 0G9
Vancouver Coastal Health Eye Care Center
Vancouver, British Columbia, V5Z 3N9
About this study
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)
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).
- Conditions
- Thyroid Eye Disease, Graves Orbitopathy, Endocrine System Diseases, Eye Diseases, Thyroid Associated Ophthalmopathy, Graves Ophthalmopathy
- Being tested
- Linsitinib, Placebo
- Keywords
- Thyroid Associated Ophthalmopathies
- Medical subject headings
- Graves Ophthalmopathy, Endocrine System Diseases, Eye Diseases, Thyroid Diseases, Orbital Diseases, Exophthalmos, Hashimoto Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LinsitinibDrug
Study medication taken twice daily by mouth
PlaceboDrug
Placebo taken twice daily by mouth
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo Arm Receives: Drug: Placebo |
| Low Dose | Active comparator | Active Arm Low Dose Linsitinib Receives: Drug: Linsitinib |
| High Dose | Active comparator | Active Arm High Dose Linsitinib Receives: Drug: Linsitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Subjects Who Are Proptosis Responders at Week 24
Proptosis response is defined as a ≥ 2 mm reduction from Baseline in the primary study eye without deterioration (≥ 2 mm increase) of proptosis in the contralateral non-study eye.
Measured: 24 weeks
Secondary outcomes (3)
Percentage of Subjects Who Are Overall Responders at Week 24
Overall response is defined as a >= 2-point reduction from baseline CAS and >= 2 mm reduction in proptosis in the primary study eye at week 24 without deterioration (>= 2-point increase) in CAS or deterioration (>= 2 mm increase) of proptosis in the contralateral non-study eye. In the event of death, the latest CAS/proptosis observations will be carried forward. Missing values of CAS and proptosis measurement in the primary study eye and contralateral non-study eye at week 24 are multiple imputed by using all available prior CAS/proptosis measures, smoking status and treatment group.
Measured: 24 weeks
Percentage of Subjects With a CAS Value of 0 or 1 at Week 24
A CAS value of 0 or 1 in primary study eye at week 24. In the event of death, the latest CAS observation will be carried forward.
Missing values of CAS at week 24 are multiple imputed by using all available prior CAS measures, smoking status and treatment group
Measured: 24 weeks
Change From Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score to Week 24.
Change from baseline to week 24 in Graves' Ophthalmology Quality of Life (GO-QoL) overall score or to last assessed value in case of death. Missing values of GO-QoL overall score up to week 24 are multiple imputed by using all available prior GO-QoL overall score measures, smoking status and treatment group.
Overall scale was measured from 0 minimum to 100 maximum (0 is worse health state and 100 is best health state)
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2022
- Study start1 Jul 2022
- Primary completion15 Oct 2024
- Study completion26 Sep 2025
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 Thyroid Eye DiseaseStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sling Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05276063
- Sponsor's protocol ID
- VGN-TED-301
- Acronym
- LIDS
- Status last verified
- Aug 2026
- First submitted
- 2 Mar 2022
- Last updated
- 23 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data collected during the trial, after deidentification will be made available.
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05276063
- Acronym / sponsor ID
- LIDS / VGN-TED-301
- Conditions
- Thyroid Eye Disease, Graves Orbitopathy, Endocrine System Diseases, Eye Diseases, Thyroid Associated Ophthalmopathy, Graves Ophthalmopathy
- Keywords
- Thyroid Associated Ophthalmopathies
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Sling Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 15 Oct 2024 (actual)
- Study completion
- 26 Sep 2025 (actual)
- First posted
- 11 Mar 2022 (actual)
- Results
- Posted 26 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo Arm |
| Low Dose | Active comparator | Drug: LinsitinibActive Arm Low Dose Linsitinib |
| High Dose | Active comparator | Drug: LinsitinibActive Arm High Dose Linsitinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
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 |
|---|---|---|
| LinsitinibStudy medication taken twice daily by mouth | Drug | High Dose, Low Dose |
| PlaceboPlacebo taken twice daily by mouth | Drug | Placebo |
Primary outcome
Percentage of Subjects Who Are Proptosis Responders at Week 24
Time frame: 24 weeks
Proptosis response is defined as a ≥ 2 mm reduction from Baseline in the primary study eye without deterioration (≥ 2 mm increase) of proptosis in the contralateral non-study eye.
3 secondary outcomes
Percentage of Subjects Who Are Overall Responders at Week 24
Time frame: 24 weeks
Percentage of Subjects With a CAS Value of 0 or 1 at Week 24
Time frame: 24 weeks
Change From Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score to Week 24.
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. All individual participant data collected during the trial, after deidentification will be made available.
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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.
30 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Linsitinib in people with Thyroid Eye Disease and Graves Orbitopathy, run by Sling Therapeutics, Inc. at 30 sites in 5 countries.
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 4 inclusion and 5 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 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Italy, Spain, United Kingdom, 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 26 Aug 2026). 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?
Percentage of Subjects Who Are Proptosis Responders at Week 24 (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Sep 2026.