TEPROTUMUMAB for Thyroid eye disease (Graves' ophthalmopathy)

Inclusion criteria

• {"criterion_text":"- Participant must provide written informed consent.\n- Participant is willing and able to comply with the protocol requirements for the duration of the trial.\n- Participant can be male or female and must be between the ages of 18 and 80 years, inclusive, at Screening.\n- 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.\n- 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.\n- 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.\n- Participant had onset of active TED symptoms (as determined by participant records) within 15 months prior to Baseline.\n- 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.\n- Participant does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the trial.\n- 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)."}

Exclusion criteria

• {"criterion_text":"- 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.\n- Participant has corneal decompensation unresponsive to medical management.\n- Participant has a decrease in CAS of ≥ 2 points between Screening and Baseline.\n- Participant has a decrease in proptosis of ≥ 2 mm between Screening and Baseline.\n- Participant had prior orbital irradiation, orbital decompression or strabismus surgery (excluding childhood strabismus surgeries unrelated to TED/Graves’ disease).\n- Participant is planning to have eyelid surgery during the trial.\n- Participant received periocular botulinum toxin injection within 12 months prior to Screening.\n- 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."}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Responder defined as 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 the specified Week."}

Secondary endpoints

• {"endpoint_text":"- Mean change from Baseline at Week XX in proptosis measurement in the study eye.","definition_or_measurement_approach":"Mean change from Baseline in proptosis measurement in the study eye at Week XX."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Responder defined as participants with ≥2-point reduction in CAS AND ≥2-mm reduction in proptosis from Baseline without corresponding deterioration (≥2-point or ≥2-mm increase) in the fellow eye at Week XX."}
• {"endpoint_text":"- Percentage of participants with a CAS value of 0 or 1 at Week XX in the study eye.","definition_or_measurement_approach":"Percentage of participants whose Clinical Activity Score (CAS) in the study eye is 0 or 1 at Week XX."}
• {"endpoint_text":"- Change from Baseline at Week XX in diplopia as ordinal response categories.","definition_or_measurement_approach":"Change from Baseline in diplopia categorized as ordinal response categories at Week XX."}
• {"endpoint_text":"- Diplopia responder rate, defined as the percentage of participants with Baseline binocular diplopia > 0 who have a reduction of ≥ 1 grade at Week XX","definition_or_measurement_approach":"Responder defined as participants with Baseline binocular diplopia >0 who achieve a reduction of ≥1 grade at Week XX."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Responder defined as participants with Baseline binocular diplopia >0 who have a diplopia score of 0 at Week XX."}
• {"endpoint_text":"- Mean change from Baseline at Week XX in the Graves’ Ophthalmopathy Quality of Life (GO-QoL) questionnaire overall score","definition_or_measurement_approach":"Mean change from Baseline in the GO-QoL questionnaire overall score at Week XX."}

Methods

• Doctor-to-patient letters (country-specific documents present: Poland, Spain, Italy, France, Germany).
• Doctor-to-doctor / GP letters (country-specific recruitment documents: e.g., GP-Letter_IT).
• Public-facing printed materials: Flyers, Posters, Brochures, Patient Journey materials (documents available for multiple countries/languages).
• Pre-screener questionnaires (country-specific pre-screener documents present).
• Advocacy materials and campaign copy (country-specific advocacy materials present).
• Recruitment brochures, inclusion-exclusion cards, retention items and summary letters (country-specific).
• Consent Flipchart and informed consent documents provided to support recruitment and consent.

France

Earliest CTIS Part Ii Submission Date

08-11-2024

Latest Decision Or Authorization Date

16-01-2025

Processing Time Days

69

Number Of Sites

3

Number Of Participants

7

Germany

Earliest CTIS Part Ii Submission Date

12-11-2024

Latest Decision Or Authorization Date

17-01-2025

Processing Time Days

66

Number Of Sites

2

Number Of Participants

7

Italy

Earliest CTIS Part Ii Submission Date

29-11-2024

Latest Decision Or Authorization Date

27-01-2025

Processing Time Days

59

Number Of Sites

4

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

23-12-2024

Latest Decision Or Authorization Date

27-01-2025

Processing Time Days

35

Number Of Sites

5

Number Of Participants

7

Poland

Earliest CTIS Part Ii Submission Date

03-12-2024

Latest Decision Or Authorization Date

20-01-2025

Processing Time Days

48

Number Of Sites

3

Number Of Participants

5

Primary sponsor

Full Name

Horizon Therapeutics USA Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

IRT Programing, Supply Management, Clinical Management, Logistics and Trade compliance; additional operational duties (codes present in registry data)

Name

Medidata Solutions Inc.

Responsibilities

Data Base Programming / Maintenance

Name

Biologics Development Services LLC

Responsibilities

Biomarker sample analysis (Immunologix Labs)

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Data Base Programming / Maintenance","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Multiple duties including IRT Programing, Supply Management, Clinical Management, Logistics and Trade compliance; other duties coded in sponsor data","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Biologics Development Services LLC","duties_or_roles":"Immunologix Labs (biomarker sample analysis)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"Sponsor duty code 3 (role specified in registry data; textual duty not provided)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"Translation Services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Clinical Trial Patient Services (Travel Management)","organisation_type":"Hospital/Clinic/Other health care facility"}