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

JRCT ID: jRCT2031240330

Registered date:11/09/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Active thyroid eye disease
• Date of first enrollment: 24/09/2024
• Target sample size: 50
• 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.

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. However, if magnetic resonance imaging (MRI) is possible, assessment should be based on a); otherwise, b) can be used. 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.Subjects with a study eye that exhibits exophthalmos of 18 mm or more, or a difference in exophthalmos of 3 mm or more between both 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.
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 have been treated with a stable dose of antithyroid drugs for at least 6 weeks prior to consent (thyroid hormone drugs should not be used in combination for at least 6 weeks before consent) and are clinically and biochemically euthyroid or hyperthyroid at the time of screening (euthyroid is defined as a normal serum FT4 level with low or normal TSH levels). Alternatively, patients with Graves' disease who have not been treated with antithyroid drugs for at least 6 weeks due to intolerable side effects (thyroid hormone drugs should not be used for at least 6 weeks before consent) and are clinically and biochemically hyperthyroid at the time of screening.

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 used systemic steroids (intravenous, oral), orbital steroid injections, or topical steroids within 3 weeks prior to consent for the treatment of thyroid eye disease or other conditions. These steroids should not be initiated during the study. However, local administration of steroids outside the orbital area (e.g., topical steroids, intra-articular steroid injections, inhaled steroids) and steroids used to manage reactions to injections are excluded.
6.Subjects who received rituximab (Rituxan) within 12 months prior to starting the investigational drug, or tocilizumab (Actemra) within 6 months prior to starting the investigational drug, or other non-steroidal immunosuppressants within 3 months prior to starting the investigational drug.
7.Subjects who received botulinum toxin treatment around the eyes within 3 months prior to starting the investigational drug.

Additional exclusion criteria are outlined in the study protocol.

Related Information

• Primary Sponsor: KIKUCHI TSUYOSHI