Environmental Exposure Unit Trial in Subjects With Ragweed-induced Allergic Rhinitis

A Randomized, Double-blind, Placebo-controlled, Environmental Exposure Unit Trial of Intranasal INI-2004 in Subjects With Ragweed-induced Allergic Rhinitis

The purpose of this trial is to see how well an experimental nasal spray, called INI-2004, works for those with allergy symptoms to ragweed. This nasal spray will compare how well 500mcg of INI-2004, given once per week for 4 weeks, works at reducing ragweed allergy symptoms in an Environmental Exposure Unit (EEU), compared to placebo.

Inclusion Criteria:

1. Must have given valid written informed consent, before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.

2. Healthy male or female, aged between 18 and 64 years, inclusive at screening.

3. Minimum 12-month history of ragweed-induced AR requiring pharmacotherapy (self-reported history accepted), history of or current positive ragweed skin prick test reaction (≥ 5mm greater than the diluent) at SV1, and a TNSS score of ≥ 6 at 2 timepoints during the SV2 ragweed allergen EEU challenge, including a "congestion" score of ≥ 2 at ≥ 1 time point.

4. Body mass index (BMI) of 17 to 39 kg/m2, inclusive, at screening. Subjects with BMI > 39 kg/m2 may be included with permission of the Sponsor.

5. Participant is medically healthy (in the opinion of the PI [or delegate]), as determined by medical history and without clinically significant abnormalities including:

   1. Physical examination without any additional clinically relevant findings
   2. Vital signs (pulse, blood pressure, respiratory rate, temperature) without clinically significant abnormalities, in the opinion of the PI (or delegate).
   3. Electrocardiogram without clinically significant abnormality at screening including QT interval corrected for Fredericia (QTcF) ≤ 450 msec for male subjects and ≤ 470 msec for female subjects. The ECG may be repeated if technically unsatisfactory (e.g. artifact) or otherwise thought not to be representative, at the discretion of the Investigator.
   4. No clinically significant findings in serum chemistry, hematology or urinalysis as judged by the PI (or delegate).

6. Female participants must be of non-child-bearing potential i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the screening visit) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or, if of child-bearing potential*:

   1. Must have a negative serum pregnancy test at the screening visit 1, and a negative urine pregnancy test at screening visit 2 and prior to all dose and EEU exposure visits.

   2. Must agree not to donate ova or attempt to become pregnant from the time of signing consent until at least 30 days after the last dose of study drug.

   3. If not exclusively in a same-sex relationship or abstinent as a committed lifestyle, must agree to use adequate contraception (which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception (See Appendix 2) from one month prior to dose administration until at least 30 days after the last dose of study drug).

      • Women who have been surgically sterilized through tubal ligation are permitted to participate, if they agree to use an additional barrier method of contraception from one month prior to the first dose of study drug, until at least 30 days after the last dose of study drug.

7. Male participants must:

   1. Agree not to donate sperm from the time of signing consent until at least 90 days after the last dose of study drug.
   2. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception (defined as use of a condom plus a highly effective method of contraception from the time of signing consent until at least 90 days after the last dose of study drug).

8. Willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures.

Exclusion Criteria:

1. Hypersensitivity or other clinically significant reaction to the study drug or its active ingredients.

2. History of perennial allergic rhinitis which may confound study results.

3. Ragweed targeted allergy immunotherapy within five years of screening.

4. Expected travel to an area with potential environmental ragweed exposure within 7 days of SV2 through Day 38.

5. History of any clinically relevant or unstable disorder which, in the opinion of the PI (or delegate) would make implementation of the protocol or interpretation of study results difficult, or that would put the subject at risk by participating in the study, including uncontrolled cardiovascular, hematologic, pulmonary, hepatic, renal, gastrointestinal, connective tissue disease, immunologic, uncontrolled endocrine/metabolic, oncologic (within the last 5 years), neurologic, and psychiatric diseases. Note: a history of fully resolved childhood asthma is not exclusionary; history of cholecystectomy is not exclusionary; history of anxiety and/or depression is permitted provided symptoms are controlled on or off approved concomitant medication for at least 6 months prior to SV1. Local malignancies with complete surgical resection (e.g. basal cell carcinoma, cervical cancer-in-situ) are not exclusionary.

6. Asthma that requires regular pharmacotherapy, is expected to require regular pharmacotherapy during study participation, or that is expected to be exacerbated by ragweed EEU challenge. Note: PRN pharmacotherapy for asthma is permitted, as long as there has been no use within 14 days prior to the first dose of study drug on Day 0. Participants must refrain from use during the study, unless medically necessary.

7. Currently experiencing symptomatic perennial rhinitis requiring medication as per PI (or delegate) judgement.

8. Use of oral or systemic steroids within 28 days of SV2, oral anti-histamines within 14 days of SV2, and intranasal medications, or any prescription or over-the-counter medication within 7 days prior to SV2 or expected use during study conduct from 7 days before Day 0 through Day 38, that would affect TNSS scores, in the opinion of the PI (or delegate). Topical steroids are allowable.

9. Any clinically relevant structural nasal abnormalities that may affect distribution of study drug in the nasopharynx i.e., nasal septal perforation, nasal polyps, other nasal malformations or history of frequent nosebleeds. Note: fully resolved abnormalities/malformations (e.g., via rhinoplasty) are permitted.

10. Upper respiratory tract infection or upper respiratory tract infection symptoms at SV2 that in the opinion of the PI (or delegate) affect TNSS score and/or other patients' safety.

11. Other active infection requiring systemic antibiotic, antifungal, or antiviral medication within 14 days prior to first dose of study drug (Day 0), unless such treatment will not interfere with the objectives of the study, in the opinion of the PI (or delegate) and with Sponsor approval.

12. Concurrent enrolment in another clinical study, or participation in another clinical study within 30 days prior to the first dose of study drug on Day 0.

13. Regular consumption of >14 standard alcoholic drinks/week where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc/Vol], 100 mL wine [12% Alc/Vol], 30 mL spirit [40% Alc/Vol]).

14. History of opioid abuse within 3 months of Screening, or the requirement for daily use of opioids for more than 7 days within one month of Screening. Definition of abuse will be as per PI or delegate's judgement.

15. Current history of drug abuse. Note: UDS testing at SV1 with positive results that result from prescription products used appropriately, that do not represent a history of abuse, are not exclusionary. Repeat assessment is permitted at the discretion of the PI (or delegate) in the instance of positive results. "False positive" results from acceptable products may be disregarded at the discretion of the PI (or delegate). At the discretion of the PI (or delegate), a positive result for delta-9-tetrahydrocannabinol (THC) may not be exclusionary, however participants are not permitted to use combustible or other cannabinoid products within 24 hours prior to each visit SV2 through Day 38

16. Current use of combustible or chewed tobacco products greater than the equivalent of 10 cigarettes per day, or unwilling to comply with restriction or abstention from all tobacco products 12 hours before each dose of study drug and each EEU session.

17. Participant is breastfeeding or pregnant or planning to breastfeed or become pregnant during the study.

18. Known substance abuse or medical, psychological, or social conditions that, in the opinion of the PI (or delegate), may interfere with the participants inclusion in the clinical study or evaluation of the clinical study results.

19. History of or current infection with Hepatitis B, Hepatitis C, or HIV.

20. Participant has donated blood or blood products within the following timeframe prior to first dose administration (Day 0):

    • Blood = 60 days; plasma = 14 days

21. Participant plans to travel to an area with known environmental ragweed exposures at any time during study participation (from SV1 through to Day 38).

22. Any other condition or prior therapy that in the opinion of the PI (or delegate) would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.