Phase 1, First in Human (FIH), Ascending Dose Study to Assess the Safety, Tolerability and Preliminary Immunogenicity of ITI-9001 in Japanese Patients With Japanese Red Cedar (JRC) Pollinosis: A Two-part Design Consisting of an Open-Label, Single-Arm Part A and a Randomized, Double-Blind, Part B
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Frequency and severity of dose-limiting toxicities (DLTs)
研究概览
简要总结
This is a Phase 1, first-in-human clinical trial to test a new treatment called ITI-9001 for people with allergies to Japanese Red Cedar (JRC) pollen-a common cause of seasonal allergies in Japan. The main goals are to find out if ITI-9001 is safe, how well people tolerate it, and whether it can trigger helpful immune responses.
详细描述
Phase I, open-label, single-arm, ascending dose study to evaluate the safety, tolerability, and preliminary immunogenicity of ITI-9001. The study will be conducted in 2 parts -Part A and Part B.
Part A is a 'dose escalation' phase where two different doses will be given (a low dose and a high dose), where the total duration of study participation for each patient will be approximately 6 months.
Part B is an 'expansion' phase using the highest tolerated dose from Part A, where a total duration of study participation for each patient will be approximately 12 months if they receive all 3 planned doses and complete all 4 subsequent visits. Part B contains ITI-9001 and a placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Part A is open-label, so no masking is used and both participants and investigators know that ITI-9001 is being administered. Part B is randomized and double-blind, meaning participants, investigators, and blinded site staff do not know whether a subject receives ITI-9001 or placebo; only the unblinded pharmacist and designated dispensing staff prepare and mask the injections. Blinding is maintained by restricting treatment information and certain biomarker data that could reveal assignment, emergency unblinding is allowed only when necessary for subject safety and must be documented.
入排标准
- 年龄范围
- 18 Months 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Signed and dated informed consent form (ICF)
- •2. Female of non-childbearing potential or male aged 18-65 years (inclusive). Women are not considered to be of childbearing potential if they have had a hysterectomy or tubal ligation, or are postmenopausal (≥12 months without menstruation, or FSH in postmenopausal range for women \<55 years)
- •3. Confirmed JCP sensitivity by positive skin prick test (wheal diameter ≥3 mm)
- •4. Confirmed JCP sensitivity by ImmunoCAP (serum JCP-specific IgE ≥ class 2)
- •5. ≥2 year history of seasonal rhinoconjunctivitis symptoms requiring medication upon JCP exposure
- •6. Contraception requirements: \
- •a. Women of non-childbearing potential: negative serum pregnancy test ≤3 days before first dose \
- •b. Men: surgically sterile, or agree to abstinence or use 2 highly effective methods of contraception during study and for 3 months after last dose if partner is of childbearing potential (male condom + oral hormonal contraceptives, intrauterine device, or intrauterine hormone-releasing system)
- •7. No significant ischemic heart disease or myocardial infarction within 6 months before first study drug administration; adequate cardiac function at screening (QTcF ≤470 msec for females or ≤450 msec for males; average of triplicate ECGs). Participants with ventricular arrhythmia assessed case-by-case
- •8. Willing and able to participate and comply with all study procedures
排除标准
- •1. Women of childbearing potential (do not meet inclusion criterion #2)
- •2. Respiratory function: \
- •a. Fever ≥38°C (100.4°F) on day of study drug administration \
- •b. FEV1 \<80% as predicted on spirometry \
- •c. Current smoker/tobacco user \
- •d. History of asthma requiring daily medication (except exercise-induced or mild intermittent asthma)
- •3. Contraindications: \
- •a. Known allergy to ITI-9001 components \
- •b. Contraindication to intramuscular injections or blood draws \
- •c. History of intolerance or severe allergic reaction to previous immunotherapy \
- •d. History of anaphylaxis requiring medical intervention (including severe reactions to mRNA vaccines)
- •4. Prior/concurrent treatments: \
- •a. Participation in another therapeutic clinical trial within 30 days before screening \
- •b. Prior or current immunotherapy for JCP \
- •c. Specific or nonspecific immunotherapy within 1 year prior to screening \
- •d. Biologics (e.g., anti-IgE, anti-IL-5, anti-TNFα) \
- •e. mRNA vaccine within 28 days before first study drug administration \
- •f. Live vaccine within 28 days or inactivated/toxoid vaccine within 7 days before first study drug administration \
- •g. Chronic (more than 30 days) systemic corticosteroids (inhaled, oral, IM, IV, potent topical) \
- •h. Inability/unwillingness to discontinue beta-blockers up to 48 hours before first study drug administration and during the study \
- •i. Inability/unwillingness to comply with washout periods for antihistamines and other allergy medications (per Table 3)
- •5. Medical history/comorbidities: \
- •a. Clinically significant abnormalities on physical exam, labs, or medical history that jeopardize safety or validity of results (except HEENT findings consistent with allergic rhinitis) \
- •b. Malignant tumor diagnosed or treated within 5 years prior to first study drug administration (except adequately treated non-melanoma skin cancer or carcinoma in situ) \
- •c. Congenital or acquired immune deficiency or suppression (e.g., malignancy, infection, chemotherapy, radiation, corticosteroids) \
- •d. History of organ transplant, hematologic malignancy, or autoimmune disease \
- •e. History of stroke, transient ischemic attack, unstable angina, myocardial infarction within 3 months prior to first study drug administration \
- •f. Symptomatic congestive heart failure (NYHA Class III-IV), unstable angina, significant arrhythmia, or LVEF \<45% \
- •g. History of myocarditis or pericarditis \
- •h. Risk factors for torsades de pointes or use of medications known to prolong QT/QTc (except low-risk premedications) \
- •i. Clinically significant gastrointestinal, renal, hepatic, neurologic, or hematologic disease \
- •j. HIV/AIDS, hepatitis B, or hepatitis C infection \
- •k. Recurrent sinusitis, urticaria, or angioedema within past 12 months prior to first study drug administration \
- •l. Symptomatic overlap with JRC pollinosis requiring regular medications \
- •m. Alcohol or drug abuse within 1 year before screening or current dependence
结局指标
主要结局
Frequency and severity of dose-limiting toxicities (DLTs)
时间窗: From enrollment to Day 382
DLTs will be summarized by frequency and severity from first study drug administration through End of Study (see timeframe below)
次要结局
未报告次要终点