A Phase III Study of KHN939 in Chinese Patients With Moderate-to-Severe Inactive Thyroid Eye Disease

Официальное название

A Multicenter, Randomized, Double-masked, Placebo-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of KHN939 in the Treatment of Moderate-to-Severe Inactive Thyroid Eye Disease (TED) in China.

Обзор

This is a multicenter, randomized, double-masked, placebo-controlled Phase 3 study to evaluate the efficacy, safety, immunogenicity, and population pharmacokinetic (PopPK) characteristics of KHN939 in Chinese patients with moderate-to-severe inactive thyroid eye disease (TED). Approximately 117 participants who meet the study eligibility criteria will be randomized in a 2:1 ratio (stratified by smoking status) to receive 8 infusions of KHN939 or placebo q3W.

Вмешательства

• Препарат KHN939
  Intravenous (IV) infusion: 20 mg/kg every 3 weeks (Q3W) for a total of 8 doses over 21 weeks
• Препарат Placebo
  Intravenous (IV) infusion: placebo every 3 weeks (Q3W) for a total of 8 doses over 21 weeks

Первичные конечные точки

• The proptosis responder rate of the study eye [Срок оценки: Week 24]

Вторичные конечные точки (12)

• Proptosis responder rate in the study eye [Срок оценки: Week 12]
• Change from baseline in proptosis measurement of the study eye [Срок оценки: week 12, week 24]
• Change in Quality of Life (GO-QoL) Scores [Срок оценки: week 12, week 24]
• Change from baseline in Clinical Activity Score (CAS) in the study eye [Срок оценки: week 12, week 24]
• Change from baseline in diplopia score [Срок оценки: week 12, week 24]
• Change from Baseline in Diplopia Questionnaire (DQ) Score [Срок оценки: Week 12, Week 24]
• Percentage of subjects with a CAS value of 0 or 1 in the study eye [Срок оценки: week 12, week 24]
• Proptosis responder rate in the non-study eye [Срок оценки: week 12, week 24]
• Change from baseline in proptosis measurement in the non-study eye [Срок оценки: week 12, week 24]
• Change from baseline in ocular motility of the study eye [Срок оценки: week 12, week 24]
• The number, incidence, severity, and relevance to study drugs or treatments of all ocular and other systemic AEs, TEAEs, AESIs, and SAEs [Срок оценки: From the Screening period through study completion, with each participant completing all study visits over approximately 28 weeks, comprising a Screening Period (up to 4 weeks), a Treatment Period (21 weeks), and a Safety Follow-up Period (3 weeks).]
• Incidence of anti-drug antibodies (ADA) and neutralizing antibodies (NAbs) [Срок оценки: Up to Week 24]

Критерии участия

Критерии включения

• Aged 18-70 years (inclusive) at the time of signing the informed consent form (ICF), male or female
• Weight between 45 kg and 100 kg (inclusive)
• Diagnosed with moderate-to-severe inactive TED:

• proptosis ≥18 mm, accompanied by at least one of the following: (a) eyelid retraction ≥2 mm; (b) moderate to severe soft tissue involvement; (c) intermittent or continuous diplopia
• CAS ≤ 2 points in each eye
• CAS ≤ 2 in each eye for 6 months prior to screening (based on medical records); or meets all of the following criteria for ≥ 6 months prior to screening (based on patient self-report or medical records): no progression of proptosis, no new-onset or progressive TED-related diplopia, no new-onset inflammatory TED symptoms
• The time since initial TED diagnosis is ≥ 2 years and < 10 years prior to screening (documented by patient history or medical records)
• Female participants of childbearing potential must have a negative serum pregnancy test during screening and agree to use an effective method of contraception from screening until 90 days after the last dose of the study drug. (Note: Women of non-childbearing potential, defined as surgically sterile or postmenopausal, are exempt.)Male participants must agree to use birth control from screening until at least 90 days after the dose of study drug.
• Able to comply with all protocol-required procedures, examinations, and symptom reporting

Критерии исключения

• Known hypersensitivity to any component of the study drug formulation, or prior hypersensitivity to any monoclonal antibodies
• Proptosis at Day 1 (pre-dose) that has decreased by ≥2 mm relative to screening
• Ocular conditions:

• Prior or investigator-assessed diagnosis of dysthyroid optic neuropathy (DON) at screening
• Corneal involvement in the study eye without improvement after appropriate treatment
• Prior orbital radiotherapy or surgery for TED in the study eye (including orbital decompression, strabismus correction, eyelid correction)
• Requires immediate or planned ophthalmic surgical intervention during the study period
• Has any pre-existing ocular condition (e.g., high myopia, anticipated cataract surgery) that, as determined by the investigator, would preclude study participation or complicate the interpretation of study results
• Prior/concomitant treatments:

• Use of oral or intravenous glucocorticoids within 30 days prior to screening
• Periorbital/periocular corticosteroid injection within 90 days of screening
• Oral or IV non-steroidal immunosuppressants within 90 days of screening
• Corticosteroid or non-steroidal immunosuppressant eye drops within 7 days of screening
• Received teprotumumab or teprotumumab N01 at any time prior to screening
• Received anti-CD20 antibody therapy within 12 months prior to screening
• Received anti-interleukin-6 receptor (anti-IL-6R) antibody therapy within 6 months prior to screening
• Received any other investigational therapy for TED at any time prior to screening (including, but not limited to, biologics targeting IGF-1R, FcRn, or TSHR)
• Received any other monoclonal antibody therapy within 90 days prior to screening
• Need for selenium or vitamin supplementation for TED treatment from 21 days pre-dose through study end (multivitamins are permitted)
• Medical history/conditions:

• Medical conditions that contraindicate study drug use, including: suspected or confirmed inflammatory bowel disease (IBD), coagulopathy, Cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 180 days, acute myocardial infarction (MI), unstable angina, or CABG/PCI within 180 days, severe arrhythmia, or severe systemic infection
• Malignancy (treated or untreated) within 5 years prior to screening, except for the following cured or non-metastatic conditions: cutaneous squamous cell carcinoma (SCC) or basal cell carcinoma (BCC), cervical or prostate carcinoma in situ (CIS), papillary thyroid carcinoma
• Uncontrolled diabetes (HbA1c ≥8.0% at screening, or initiation of a new diabetes medication, or a >10% dose adjustment to an existing diabetes medication within 60 days prior to screening)
• Poorly controlled thyroid function: defined as FT3 or FT4 deviating ≥50% from local laboratory normal range (≥1.5×ULN or ≤0.5×LLN)
• Uncontrolled hypertension: defined as SBP ≥160 mmHg or DBP ≥100 mmHg; renal artery stenosis; or other evidence of clinically unstable blood pressure
• 12-lead ECG with a heart rate <50 or >100 bpm and evidence of active cardiac disease; or any screening ECG abnormality that, in the investigator's opinion, confounds subsequent interpretation, particularly QTcF >450 ms in males or >470 ms in females
• Laboratory exclusions at screening:

• Alanine aminotransferase (ALT) >3 × ULN
• Aspartate aminotransferase (AST) >3 × ULN
• Serum creatinine(Cr) ≥1.5 × ULN, or glomerular filtration rate (GFR) <30 mL/min/1.73 m² (MDRD formula)
• Clinically significant ear disease, prior ear surgery, hearing impairment, or abnormal pure-tone audiometry (defined as a mean bone conduction threshold ≥25 dB at 0.5, 1, 2, 4 kHz, or ≥40 dB at any frequency)
• Positive for HBsAg with HBV-DNA >1000 IU/mL or currently receiving anti-HBV therapy; positive for HIV antibody or HCV antibody; or active syphilis
• Participation in any drug, vaccine, or device clinical trial within 3 months prior to screening, or currently within follow-up or within 5 half-lives of another study
• Female subjects who are pregnant or lactating
• Any other condition deemed by the investigator as inappropriate for study participation

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University — Шанхай

Идентификаторы

NCT: NCT07720648 · KHN939-60102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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