Human IgG1 monoclonal antibody against thyrotropin receptor for Graves' disease | Thyroid eye disease

Inclusion criteria

• {"criterion_text":"- Subjects must satisfy all the following criteria to be enrolled in the study 1. Is a male or female subject aged 18 to 75 years of age inclusive, at the time of signing and dating the informed consent form (ICF)."}
• {"criterion_text":"- 2. Must sign and date the ICF indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study."}
• {"criterion_text":"- 3. Have clinically confirmed Graves’ disease with active thyroid eye disease at screening and baseline, with the study eye satisfying criterion a) or b). Criterion a) will be used if magnetic resonance imaging (MRI) is available and criterion b) will be used if not. a) Have inflammatory hypertrophy of the extraocular muscles as shown by MRI according to the criteria of the 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. b) The Clinical activity score (CAS) is at least 3."}
• {"criterion_text":"- 4. Has exophthalmos of ≥18 mm in the study eye, or if <18mm in the study eye there is at least 3 mm greater proptosis in the study eye compared to the fellow eye."}
• {"criterion_text":"- 5. Have any symptoms of eyelid retraction, soft-tissue findings, or diplopia as defined in the criteria for moderate to severe eye disease in the 2021 EUGOGO clinical practice guidelines for the medical management of Graves' orbitopathy."}
• {"criterion_text":"- 6. Has self-reported symptoms of active thyroid eye disease within the 12 months prior to Screening."}
• {"criterion_text":"- 7. Has Graves' disease whose underlying condition is controlled and has normal thyroid function at the time of screening or has mild hypothyroidism or hyperthyroidism.Every effort should be made to maintain thyroid function throughout the study”."}
• {"criterion_text":"- 8. Is a female of childbearing potential or male with a female partner of childbearing potential who consents to use acceptable contraceptive methods as defined in the protocol. Additional inclusion criteria are outlined in the study protocol."}

Exclusion criteria

• {"criterion_text":"- Individuals who meet any of the following criteria will be excluded from the study : 1. Has dysthyroid optic neuropathy and/or very severe eye disease (with the risk of blindness) that features ulceration, perforation or necrosis of the cornea and requires urgent therapeutic intervention."}
• {"criterion_text":"- 2. Whose CAS decreased by 2 or more points in the study eye from screening to baseline"}
• {"criterion_text":"- 3. Whose exophthalmos decreased by 2 mm or more in the study eye from screening to baseline."}
• {"criterion_text":"- 4. Has a history of orbital radiotherapy or surgery for thyroid eye disease."}
• {"criterion_text":"- 5. Has received a systemic corticosteroid (IV or orally), intraorbital corticosteroid injection, or ophthalmic corticosteroid drug for treating thyroid eye disease or another medical condition within the 3 weeks prior to providing informed consent. None of these corticosteroid treatments may be started during the study period. This excludes corticosteroids that are locally administered to an area not near the orbits (e.g., topical corticosteroids, intraarticular corticosteroid injections, and inhaled corticosteroids) and corticosteroids for treating infusion-related reactions"}
• {"criterion_text":"- 6. Has had any previous systemic treatment with rituximab (Rituxan®) within the 12 months prior to the start of study drug administration, tocilizumab (Actemra®) within the 6 months prior to the start of study drug administration, or any systemic non-steroid immunosuppressive agent within the 3 months prior to the start of study drug administration."}
• {"criterion_text":"- 7. Have received treatment around the eyes with botulinum toxin within the 3 months prior to the start of study drug administration."}
• {"criterion_text":"- 8.Has a pre-existing ophthalmic disease that, in the opinion of the investigator, would preclude study participation or complicate interpretation of the study results Additional exclusion criteria are outlined in the study protocol."}

Primary endpoints

• {"endpoint_text":"- Exophthalmos improvement rate at Week 24* *The proportion (%) of subjects who achieve at least a 2-mm decrease in exophthalmos of the study eye from baseline and have no worsening in exophthalmos (defined as an increase of at least 2 mm) in the fellow eye.","definition_or_measurement_approach":"The proportion (%) of subjects who achieve at least a 2-mm decrease in exophthalmos of the study eye from baseline and have no worsening in exophthalmos (defined as an increase of at least 2 mm) in the fellow eye."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in the ratio of signal intensity in the extraocular muscles shown by MRI. Change from baseline in the GO-QOL score Change from baseline in the CAS. Change from baseline in exophthalmos measurement . Change from baseline in diplopia grade (Bahn-Gorman scale) (diplopia improvement rate) Change from baseline in retrobulbar volume shown by MRI","definition_or_measurement_approach":"Change from baseline assessments using MRI for signal intensity in extraocular muscles; validated GO-QOL score changes; Clinical Activity Score (CAS) change from baseline; exophthalmos measurement change from baseline; diplopia graded by Bahn-Gorman scale (diplopia improvement rate); retrobulbar volume measured by MRI change from baseline."}
• {"endpoint_text":"- Safety, determined by: a) AEs b) Vital sign measurements c) 12-lead ECG measurements d) Laboratory test results e) Physical examination results f) Eye examination results Changes in levels of TSH, thyroid hormones (FT4 and FT3), TSH receptor autoantibodies and stimulating TSH receptor autoantibodies Change over time in blood concentrations of K1-70 Change over time in blood concentrations of Anti-drug antibodies","definition_or_measurement_approach":"Safety assessed by recording adverse events, vital signs, 12-lead ECGs, laboratory tests, physical and eye examinations; measurements of TSH, FT4, FT3, TSH receptor autoantibodies; PK: blood concentrations of K1-70 and anti-drug antibodies over time."}

Methods

• Site-based recruitment via participating hospitals/clinics (hospital sites listed for Italy and Spain).
• Doctor letters (document: K2_AV7-K1-70-IV-002_Doctor Letter_ITA_ITA_Public and ESP versions) to inform/engage referring clinicians.
• Patient letters and patient-facing brochures (documents: Patient Lett / Patient-Letter, Recruitment Brochure, Recruitment-Brochure) to invite and inform potential participants.
• Fact sheets and recruitment arrangements documents (K1_AV7-K1-70-IV-002_Recruitment-Arrang_ITA_ENG_Public and K1_AV7-K1-70-IV-002_Recruitment-Arrangements_ESP_Public) indicating country-specific recruitment materials for Italy and Spain.

Italy

Earliest CTIS Part Ii Submission Date

03-12-2025

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

75

Number Of Sites

4

Number Of Participants

30

Spain

Earliest CTIS Part Ii Submission Date

15-01-2026

Latest Decision Or Authorization Date

05-02-2026

Processing Time Days

21

Number Of Sites

5

Number Of Participants

20

Primary sponsor

Full Name

Av7 Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

PPD Global Limited

Responsibilities

Numerous operational roles as listed in sponsorDuties (codes provided in submission); overall CRO functions indicated in product documentation and protocol (e.g., clinical operations, data management, monitoring).

Name

PPD Global Central Labs

Responsibilities

Samples storage and laboratory services (Samples Storage; sponsorDuties code 15 and code 4).

Name

Bioclinica Inc.

Responsibilities

Image central reading (MRI) (sponsorDuties code 15).

Name

Suvoda LLC

Responsibilities

Clinical operations / site technology support (sponsorDuties code 3).

Name

Medidata Solutions Inc.

Responsibilities

eClinical platform/provider services (sponsorDuties code 7).

Name

Bml Inc.

Responsibilities

Bioanalytical services: PK & ADA Serum Samples and TSAb & TRAb (sponsorDuties code 15).

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Image central reading (MRI) (sponsorDuties code 15)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"PPD Global Limited","duties_or_roles":"sponsorDuties codes: [1,10,11,12,13,14,2,5,6,8,9] (codes as provided)","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Samples Storage (sponsorDuties code 15); code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties code: [3]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Japan","full_name":"Bml Inc.","duties_or_roles":"PK & ADA Serum Samples and TSAb & TRAb (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}