Overview
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.
Description
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.
Eligibility
Inclusion Criteria:
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
Exclusion Criteria:
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
