Trial of INI-2004 in Healthy Volunteers and Participants With Allergic Rhinitis.

A Randomised, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Trial of INI-2004 in Healthy Volunteers and Participants With Allergic Rhinitis.

This is a Phase I/Ib, randomised, double-blind, placebo-controlled study of INI-2004, administered as single or multiple doses. This study will be conducted in two parts: Phase I single ascending dose (SAD) and Phase Ib multiple ascending dose (MAD).

This is a Phase I/Ib, randomised, double-blind, placebo-controlled study of INI-2004, administered as single or multiple doses.

Phase I (SAD) - Healthy Participants will be enrolled and randomised to 4 dose cohorts (n=8 per cohort) to receive single ascending doses of INI-2004 or placebo (ratio 3:1 active: placebo). Dosing in each cohort will commence with two sentinels, with one of the two sentinels randomised to receive INI-2004 and the other randomised to receive placebo. The safety and tolerability of each sentinel participant will be monitored in the clinic until Day 2 and will be reviewed by the Principal Investigator (PI) prior to dosing the remainder of participants in each cohort. The decision to escalate between cohorts will be made by a safety review committee (SRC) following completion of the Day 3 visit for at least 6 out of 8 participants in the cohort. Cohorts will be dosed in an escalating order.

Phase Ib (MAD) - Phase Ib (MAD) may commence following completion of SAD Cohort 3 or SAD Cohort 4.

Up to 3 dose levels are planned to be evaluated. To be eligible for study inclusion, participants must have a positive response to the ragweed nasal allergen challenge at screening. Cohorts will be dosed in escalating order, with participants in each cohort (up to n=12 per cohort) randomised in blocks of 4 subjects to receive INI-2004 or placebo at a ratio of 3:1 (active:placebo). INI-2004 or placebo will be administered QW, commencing 2 weeks after administration of the second ragweed nasal allergen challenge.

Inclusion Criteria (Phase 1):

1. Participant is willing to refrain from consuming food or beverages containing caffeine and/or xanthene products, within 24 hours prior to check-in on Day -1.
2. Female participants must be of non-child-bearing potential i.e., surgically sterilised at least 6 weeks before the screening visit or postmenopausal.

Inclusion Criteria Phase Ib (Multiple Ascending Dose)

1. Minimum 2 year history of ragweed-induced AR requiring pharmacotherapy (self-reported history accepted) and a positive ragweed skin prick test reaction at Screening Visit.
2. Participant is willing to refrain from consuming food or beverages containing caffeine, within 24 hours prior to each clinic visit.
3. Female participants must be of non-child-bearing potential i.e., surgically sterilised or postmenopausal.

Exclusion Criteria Phase I and Phase Ib (MAD):

1. Hypersensitivity or other clinically significant reaction to the study drug or its active ingredients.
2. Current treatment or use of any prescription medication within 14 days prior to admission to the clinic on Day -1 of active seasonal and perennial allergic rhinitis, non-allergic rhinitis, rhinosinusitis, or asthma. This includes antihistamines, asthma preventers and relievers, nasal decongestants, IN corticosteroids, and immunotherapy or use of over-the-counter medication/vitamins/supplements within 7 days prior to the first dose of study drug. Exceptions include contraception, paracetamol and standard doses of multivitamins.
3. Any clinically relevant structural nasal abnormalities, i.e., nasal septal perforation, nasal polyps, other nasal malformations or history of frequent nosebleeds, upper respiratory tract infection within 2 weeks prior to screening or first dose administration.
4. History of recurrent migraine headaches within 4 weeks prior to screening.
5. Positive alcohol breath, urine test, HBsAg, HepC virus antibody, or HIV antibody tests.
6. Participant has donated blood or blood products within 3 months prior to first dose administration.
7. Use of tobacco products or nicotine-containing products (including smoking cessation aids such as gum or patches.
8. Participant plans to travel to an area with known environmental ragweed exposures at any time during study participation.