A trial to investigate teprotumumab mg/ml subcutaneous administration compared with placebo in male and female adult participants with moderate-tosevere active thyroid eye disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Horizon Therapeutics USA Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

20 Feb 2025 → ongoing

Decision date (initial)

2025-01-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Horizon Therapeutics USA Inc.

External identifiers

EU CT number

2024-515702-63-00

WHO UTN

U1111-1307-5565

ClinicalTrials.gov

NCT06248619

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

To evaluate the effect of teprotumumab versus placebo on the proptosis responder rate (ie, the percentage of participants with a ≥ 2-mm reduction from Baseline in the study eye without deterioration [≥ 2-mm increase] of proptosis in the fellow eye) at XX Week

Secondary objectives 1

1. To evaluate the effect of teprotumumab versus placebo on measures of clinical efficacy and patient-reported outcomes at XX Week

Conditions and MedDRA coding

Moderate-to-Severe Active Thyroid Eye Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participant must provide written informed consent.
2. Participant can be male or female and must be between the ages of 18 and 80 years, inclusive, at Screening.
3. Participant must have a clinical diagnosis of Graves’ disease associated with active TED with a CAS ≥ 3 (on the 7-item scale) for the most severely affected eye at Screening and Baseline.
4. Participant must have moderate-to-severe active TED (not sight-threatening but has an appreciable impact on daily life), usually associated with 1 or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement and/or inconstant or constant diplopia.
5. Participant has proptosis ≥ 3 mm from Baseline (prior to diagnosis of TED), as estimated by treating physician, and/or proptosis ≥ 3 mm above normal for race and gender.
6. Participant had onset of active TED symptoms (as determined by participant records) within 15 months prior to Baseline.
7. Participants must be euthyroid with the baseline disease under control or have mild hypoor hyperthyroidism (defined as free thyroxine [FT4] and free triiodothyronine [FT3] levels < 50% above or below the normal limits) at Screening. Every effort should be made to correct the mild hypo- or hyperthyroidism promptly and to maintain the euthyroid state for the full duration of the trial.
8. Participant does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the trial.
9. Women of childbearing potential must have a negative serum pregnancy test at Screening and negative urine pregnancy tests at all protocol-specified time points (ie, prior to each dose and throughout participation in the trial).
10. Participant is willing and able to comply with the protocol requirements for the duration of the trial.

Exclusion criteria 8

1. Participant has decreased best-corrected visual acuity due to optic neuropathy, defined by a decrease in vision of 2 lines on the Snellen chart (or equivalent), new visual field defect or color defect secondary to optic nerve involvement within the last 6 months.
2. Participant has corneal decompensation unresponsive to medical management.
3. Participant has a decrease in CAS of ≥ 2 points between Screening and Baseline.
4. Participant has a decrease in proptosis of ≥ 2 mm between Screening and Baseline.
5. Participant had prior orbital irradiation, orbital decompression or strabismus surgery (excluding childhood strabismus surgeries unrelated to TED/Graves’ disease).
6. Participant is planning to have eyelid surgery during the trial.
7. Participant received periocular botulinum toxin injection within 12 months prior to Screening.
8. Participant has any systemic use of a steroid (IV or oral) or steroid eye drops for the treatment of TED or other conditions within 3 weeks prior to Screening. Exceptions include local administration (excluding periocular), eg, topical, intra-articular, and inhaled steroids, as well as steroids used to treat infusion reactions.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proptosis responder rate (percentage of participants with a ≥ 2-mm reduction from Baseline in proptosis in the study eye without deterioration [≥ 2-mm increase] of proptosis in the fellow eye) at XX Week

Secondary endpoints 7

1. Mean change from Baseline at Week XX in proptosis measurement in the study eye.
2. Overall responder rate (percentage of participants with ≥ 2-point reduction in Clinical Activity Score [CAS] AND ≥ 2-mm reduction in proptosis from Baseline, provided there is no corresponding deterioration [≥ 2-point/mm increase] in CAS or proptosis in the fellow eye) at Week XX.
3. Percentage of participants with a CAS value of 0 or 1 at Week XX in the study eye.
4. Change from Baseline at Week XX in diplopia as ordinal response categories.
5. Diplopia responder rate, defined as the percentage of participants with Baseline binocular diplopia > 0 who have a reduction of ≥ 1 grade at Week XX
6. Complete diplopia responder rate, defined as the percentage of participants with a Baseline binocular diplopia score > 0 and a score of 0 at Week XX
7. Mean change from Baseline at Week XX in the Graves’ Ophthalmopathy Quality of Life (GO-QoL) questionnaire overall score

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Horizon Therapeutics USA Inc.

Sponsor organisation

Horizon Therapeutics USA Inc.

Address

1 Horizon Way

City

Deerfield

Postcode

60015-3888

Country

United States

Scientific contact point

Organisation

Horizon Therapeutics USA Inc.

Contact name

Medical Information

Public contact point

Organisation

Horizon Therapeutics USA Inc.

Contact name

Medical Director

Third parties 6

Locations

5 EU/EEA countries · 17 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 94 files

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

Application history

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