NCT07726147 - Phase 1, First in Human (FIH), Open-Label, Single-Arm, Ascending Dose Study to Assess the Safety, Tolerability and Preliminary Immunogenicity of ITI-9001 in Japanese Patients With Japanese Red Cedar (JRC) Pollinosis | Crick | Crick
Phase 1, First in Human (FIH), Open-Label, Single-Arm, Ascending Dose Study to Assess the Safety, Tolerability and Preliminary Immunogenicity of ITI-9001 in Japanese Patients With Japanese Red Cedar (JRC) Pollinosis
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.
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.
ITI-9001 is a self-amplifying RNA (saRNA) immunotherapy formulated with lipid nanoparticles for intramuscular injection. The saRNA encodes a CryJ2-LAMP-1 fusion protein, targeting Japanese Red Cedar (JRC) pollen allergy. ITI-9001 is designed to enhance antigen presentation and stimulate robust immune responses, aiming to reduce allergic symptoms in JCP-sensitive patients.
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: \<br\> a. Women of non-childbearing potential: negative serum pregnancy test ≤3 days before first dose \<br\> 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: \<br\> a. Fever ≥38°C (100.4°F) on day of study drug administration \<br\> b. FEV1 \<80% as predicted on spirometry \<br\> c. Current smoker/tobacco user \<br\> d. History of asthma requiring daily medication (except exercise-induced or mild intermittent asthma)
3. Contraindications: \<br\> a. Known allergy to ITI-9001 components \<br\> b. Contraindication to intramuscular injections or blood draws \<br\> c. History of intolerance or severe allergic reaction to previous immunotherapy \<br\> d. History of anaphylaxis requiring medical intervention (including severe reactions to mRNA vaccines)
4. Prior/concurrent treatments: \<br\> a. Participation in another therapeutic clinical trial within 30 days before screening \<br\> b. Prior or current immunotherapy for JCP \<br\> c. Specific or nonspecific immunotherapy within 1 year prior to screening \<br\> d. Biologics (e.g., anti-IgE, anti-IL-5, anti-TNFα) \<br\> e. mRNA vaccine within 28 days before first study drug administration \<br\> f. Live vaccine within 28 days or inactivated/toxoid vaccine within 7 days before first study drug administration \<br\> g. Chronic (more than 30 days) systemic corticosteroids (inhaled, oral, IM, IV, potent topical) \<br\> h. Inability/unwillingness to discontinue beta-blockers up to 48 hours before first study drug administration and during the study \<br\> i. Inability/unwillingness to comply with washout periods for antihistamines and other allergy medications (per Table 3)
5. Medical history/comorbidities: \<br\> 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) \<br\> 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) \<br\> c. Congenital or acquired immune deficiency or suppression (e.g., malignancy, infection, chemotherapy, radiation, corticosteroids) \<br\> d. History of organ transplant, hematologic malignancy, or autoimmune disease \<br\> e. History of stroke, transient ischemic attack, unstable angina, myocardial infarction within 3 months prior to first study drug administration \<br\> f. Symptomatic congestive heart failure (NYHA Class III-IV), unstable angina, significant arrhythmia, or LVEF \<45% \<br\> g. History of myocarditis or pericarditis \<br\> h. Risk factors for torsades de pointes or use of medications known to prolong QT/QTc (except low-risk premedications) \<br\> i. Clinically significant gastrointestinal, renal, hepatic, neurologic, or hematologic disease \<br\> j. HIV/AIDS, hepatitis B, or hepatitis C infection \<br\> k. Recurrent sinusitis, urticaria, or angioedema within past 12 months prior to first study drug administration \<br\> l. Symptomatic overlap with JRC pollinosis requiring regular medications \<br\> m. Alcohol or drug abuse within 1 year before screening or current dependence
Locations (1)
Medical Corporation Shinanokai SHINANOZAKA Clinic
Tokyo, Shinjuku-ku, Japan
RECRUITING
Outcomes
Primary Outcomes
Frequency and severity of dose-limiting toxicities (DLTs)
DLTs will be summarized by frequency and severity from first study drug administration through End of Study (see timeframe below)