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A Phase II Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate K1-70 in Japanese Patients with Active Thyroid Eye Disease

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Active thyroid eye disease
Date of first enrollment	16/10/2024
Target sample size	50
Countries of recruitment
Study type	Interventional
Intervention(s)	This clinical trial will be conducted with two cohorts: a low-dose cohort (50 mg) and a high-dose cohort (100 mg). On Day 1, subjects will be randomly assigned to either the K1-70 group or the placebo group in a 1:1 ratio. K1-70 or placebo will be administered once every 6 weeks for a total of 4 doses.

Outcome(s)

Primary Outcome	Proptosis Improvement Rate at Week 24* *Proptosis Improvement Rate: The percentage (%) of patients whose proptosis in the study eye has decreased by 2 mm or more from baseline without a worsening (an increase of 2 mm or more) in the proptosis of the fellow eye.
Secondary Outcome

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	< 75age old
Gender	Both
Include criteria	Subjects must satisfy all of the following criteria to be enrolled in the study: 1. Men and women aged 18 years or older but under 75 years at the time of signing the consent form. 2. Subjects who understand the purpose and procedures of this clinical trial and sign the consent form indicating their willingness to participate. 3. Subjects clinically diagnosed with Graves' disease with active thyroid eye disease at the time of screening and baseline, and whose study eye meets either a) or b) below. a) Subjects showing inflammatory enlargement of the extraocular muscles on MRI according to the 2023 (third draft) criteria for the diagnosis and treatment guidelines of malignant exophthalmos (thyroid eye disease) by the Japan Thyroid Association and Japan Endocrine Society. b) Subjects with a Clinical Activity Score (CAS) of 3 or higher. 4. Among patients with moderate to sever thyroid eye disease, those who exhibit any of following degrees of proptosis at baseline. a) Prpptosis is at least 18 mm in the study eye. b) An increase of 3mm or more in the study eye compared to before the onset of active thyroid eye disease. c) A difference of 3 mm or more between the left and right eyes. 5. Subjects who exhibit any of the symptoms listed under the criteria for moderate to severe eye disease in the 2023 (third draft) diagnosis and treatment guidelines for malignant exophthalmos (thyroid eye disease) by the Japan Thyroid Association and Japan Endocrine Society, such as eyelid retraction, soft tissue involvement, or diplopia in the study eye. 6. Subjects who developed symptoms of active thyroid eye disease within 12 months prior to the baseline (self-reported). 7. Patients with Graves' disease who, at the time of screening, have their underlying condition under control and either normal thyroid function, mild hypothyroidism, or hyperthyroidism. Every effort should be made to maintain stable thyroid function throughout the duration of the trial. Additional inclusion criteria are outlined in the study protocol.
Exclude criteria	Subjects who meet any of the following criteria will be excluded from participating in this clinical trial. 1. Patients with dysthyroid optic neuropathy (DON) and/or corneal ulcers, perforation, or necrosis requiring immediate treatment intervention (severe eye disease with a risk of blindness). 2. Subjects whose Clinical Activity Score (CAS) of the study eye decreased by 2 points or more between screening and baseline. 3. Subjects whose exophthalmos of the study eye decreased by 2 mm or more between screening and baseline. 4. Subjects with a history of orbital radiation or surgery for thyroid eye disease. 5. Patients who have received a systemic corticosteroid (intravenously or orally), intraorbital corticosteroid injection, or opthalmic corticosteroid drug for treating thyroid eye disease or another medical condition within 3 weeks prior to 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, inhaled corticosteroids) and corticosteroids for treating infusion related reactions. 6. Individuals who have received had any previous treatment with rituximab (Rituxan) within 12 months prior to the start of study drug treatment, or who have received tocilizumab (Actemra) within 6 months prior to the start of study drug treatment, or who have received teprotumumab (Tepezza) within 4 months prior to the start of study drug treatment, or who have received any non-steroid immunosuppressive agent within 3 months prior to the start of study drug treatment. 7. Subjects who received botulinum toxin treatment around the eyes within 3 months prior to starting the investigational drug. 8. Individuals with current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones, or mild or treatment-stable liver disease). Additional exclusion criteria are outlined in the study protocol.