A Study to Evaluate Linsitinib in Subjects with Active, Moderate to Severe Thyroid Eye Disease (TED)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sling Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

26 Oct 2023 → 6 Jun 2025

Decision date (initial)

2023-07-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Sling Therapeutics, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Others, Safety, Efficacy

to study the effect of
linsitinib on the proptosis responder rate at
Extension Study Week 24 for eligible subjects
completing Week 24 of the lead-in study
VGN-TED-301. Responder rate is the
percentage of subjects with a ≥ 2 mm
reduction from Baseline in the primary study
eye without deterioration (≥2 mm increase) of
proptosis in the contralateral non-study eye.

Secondary objectives 1

1. 1. Evaluate the effect of linsitinib on the mean change from Baseline through Extension Study Week 24 in proptosis measurement in the primary study eye. 2. Evaluate the effect of linsitinib on the overall responder rate (percentage of subjects with ≥ 2-point reduction in 7-point Clinical Activity Scale (CAS) and ≥ 2mm reduction in proptosis from Baseline, provided there is no corresponding deterioration (≥ 2-point/mm increase) in CAS or proptosis in the contralateral non-study eye at Week 24. 3. Evaluate the effect of linsitinib on the percentage of subjects with a CAS value of 0 or 1 through Extension Study Week 24 in the primary study eye. 4. Evaluate the effect of linsitinib on the mean change from Baseline through Extension Study Week 24 in the Graves’ Ophthalmopathy Quality of Life (GOQoL) questionnaire overall score.

Conditions and MedDRA coding

Thyroid Eye Disease

Study design 1 period

Regulatory references

Plan to share IPD

Yes

IPD plan description

Data will be shared: All of the individual participant data collected during the trial, after deidentification. When: Beginning 3 months and ending 5 years following article publication. Type of analyses: to achieve aims in the approved proposal. Mechanism use: Proposals should be directed to xxx@yyy. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third-party website (Link to be included)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Subject who completed the 24-week double-mask period of VGN-TED-301 and are proptosis non-responders (< 2 mm reduction in proptosis in the study eye) at Week 24 of VGN-TED-301 study or proptosis responders at Week 24 who relapse (see Section 3.1.2) during the Follow-Up period of VGN-TED-301. 2. Subject has not received any treatment for TED since Week 24 of VGN-TED-301. 3. 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 Baseline. Every effort should be made to correct mild hypo- or hyperthyroidism promptly and maintain the euthyroid state for the duration of the clinical trial. If T3 and/or T4 values are outside protocol limits, the patient may be eligible for a re-test after consultation with the medical monitor. 4. Does not require immediate ophthalmic surgery, radiotherapy to orbits or other ophthalmological intervention at the time of Baseline and is not planning for any such treatment during the course of the study. Please refer to the protocol for a complete list of inclusion criteria.

Exclusion criteria 1

1. 1. QTcF prolongation at Baseline; mean QTcF interval > 450msec (males); and >470 msec (females) and TdP risk factors, e.g., hypokalemia and family history of Congenital Long QT syndrome. 2. Alanine aminotransferase (alt) or aspartate aminotransferase (AST) > 3 times the upper limit of normal (ULN) according to age at Baseline. 3. Serum creatinine > 2 x ULN for the reference range laboratory according to age at Baseline. 4. Prior IGF-1R inhibitor therapy for any condition. Please refer to the protocol for a complete list of exclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proptosis responder rate at Extension study Week 24. The definition of responder rate, unchanged from the main VGN-TED-301 study, is the percentage of subjects with a ≥ 2 mm reduction from Baseline in the primary study eye without deterioration (≥ 2 mm increase) of proptosis in the contralateral non-study eye.

Secondary endpoints 1

1. 1. Mean change from Baseline through Week 24 in proptosis measurement in the primary study eye. 2. Overall responder rate (percentage of subjects with ≥ 2-point reduction in Clinical Activity Scale (CAS) and ≥ 2mm reduction in proptosis from Baseline, provided there is no corresponding deterioration (≥ 2- point/ mm increase) in CAS or proptosis in the contralateral non-study eye through Week 24.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sling Therapeutics Inc.

Sponsor organisation

Sling Therapeutics Inc.

Address

455 East Eisenhower Parkway Suite 300, Pmb 1048 Pmb 1048

City

Ann Arbor

Postcode

48108-3324

Country

United States

Scientific contact point

Organisation

Sling Therapeutics Inc.

Contact name

Clinical Operations

Public contact point

Organisation

Sling Therapeutics Inc.

Contact name

Clinical Operations

Third parties 7

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications