Clinical trial NCT06038279: Trial of INI-2004 in Healthy Volunteers and Participants With Allergic Rhinitis.
Official title: A Randomised, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Trial of INI-2004 in Healthy Volunteers and Participants With Allergic Rhinitis.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Allergic Rhinitis Due to Weed Pollen
Allergic Rhinitis
Lead sponsor: Inimmune Corporation
Sponsor class: INDUSTRY
Collaborators: name: Avance Clinical Pty Ltd.
First posted: 2023-09-14
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 (SAD) and Phase Ib (MAD).
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence, severity and relationship of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and TEAEs leading to discontinuation of study treatment after a single ascending Dose (SAD)
timeFrame: Baseline, Day 1 then daily through to Day 7 End of Study Visit
measure: Incidence, severity and relationship of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and TEAEs leading to discontinuation of study treatment after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0, Day 14, 21, 28, 35 through to Day 58 End of Study Visit
measure: Number of Participants with a Change from baseline in Vital signs measurements after a single ascending Dose (SAD)
timeFrame: Baseline, Day 1 through to Day 7 End of Study Visit
measure: Number of Participants with a Change from baseline in Vital signs measurements after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0 through to Day 58 End of Study Visit
measure: Change from baseline in 12-lead electrocardiogram parameters after a single ascending Dose (SAD)
timeFrame: Baseline, Day 1 through to Day 7 End of Study Visit
measure: Change from baseline in 12-lead electrocardiogram parameters after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0 through to Day 58 End of Study Visit
measure: Number of Participants with a Change from baseline in Clinical laboratory results after a single ascending Dose (SAD)
timeFrame: Baseline, Day 2 through to Day 7 End of Study Visit
measure: Number of Participants with a Change from baseline in Clinical laboratory results after a single ascending Dose (SAD)
timeFrame: Baseline, Day 2 through to Day 7 End of Study Visit
measure: Number of Participants with a Change from baseline in Clinical laboratory results after a single ascending Dose (SAD)
timeFrame: Baseline, Day 2 through to Day 7 End of Study Visit
measure: Number of Participants with a Change from baseline in Clinical laboratory results after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0, Day 14 and Day 58 End of Study Visit
measure: Number of Participants with a Change from baseline in Clinical laboratory results after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0, Day 14 and Day 58 End of Study Visit
measure: Number of Participants with a Change from baseline in Clinical laboratory results after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0, Day 14 and Day 58 End of Study Visit
measure: Change from baseline in Nasal symptoms after a single ascending Dose (SAD)
timeFrame: Baseline, Day 1 through to Day 7 End of Study Visit
measure: Change from baseline in Nasal symptoms after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0 through to Day 58 End of Study Visit
measure: Change from baseline in Nasal irritancy after a single ascending Dose (SAD)
timeFrame: Baseline, Day 1 through to Day 7 End of Study Visit
measure: Change from baseline in Nasal irritancy after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0 through to Day 58 End of Study Visit
measure: Change from baseline in Spirometry after a single ascending Dose (SAD)
timeFrame: Baseline, Day 1 through to Day 7 End of Study Visit
measure: Change from baseline in Spirometry after a single ascending Dose (SAD)
timeFrame: Baseline, Day 1 through to Day 7 End of Study Visit
measure: Change from baseline in Spirometry after a single ascending Dose (SAD)
timeFrame: Baseline, Day 1 through to Day 7 End of Study Visit
measure: Change from baseline in Spirometry after a single ascending Dose (SAD)
timeFrame: Baseline, Day 1 through to Day 7 End of Study Visit
measure: Change from baseline in Spirometry after a single ascending Dose (SAD)
timeFrame: Baseline, Day 1 through to Day 7 End of Study Visit
measure: Change from baseline in Spirometry after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0 through to Day 58 End of Study Visit
measure: Change from baseline in Spirometry after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0 through to Day 58 End of Study Visit
measure: Change from baseline in Spirometry after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0 through to Day 58 End of Study Visit
measure: Change from baseline in Spirometry after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0 through to Day 58 End of Study Visit
measure: Change from baseline in Spirometry after multiple ascending doses (MAD)
timeFrame: Baseline = Day 0 through to Day 58 End of Study Visit
Secondary outcomes:
measure: Effectiveness of INI-2004 on nasal congestion will be assessed by response to the ragweed allergen challenge (Phase Ib [MAD] only) on Days 14, 21, 23, 28, 35, 37, 51 and 58 compared to baseline (Day 0)
timeFrame: Baseline = Day 0 through to Day 58
measure: Effectiveness of INI-2004 on peak nasal inspiratory flow will be assessed by response to the ragweed allergen challenge (Phase Ib [MAD] only) on Days 14, 21, 23, 28, 35, 37, 51 and 58 compared to baseline (Day 0)
timeFrame: Baseline = Day 0 through to Day 58
measure: Effectiveness of INI-2004 on nasal symptoms will be assessed by response to the ragweed allergen challenge (Phase Ib [MAD] only) on Days 23, 37, 51 and 58 compared to baseline (Day 0)
timeFrame: Baseline = Day 0 through to Day 58
measure: Effectiveness of INI-2004 on nasal irritancy will be assessed by response to the ragweed allergen challenge (Phase Ib [MAD] only) on Days 23, 37, 51 and 58 compared to baseline (Day 0)
timeFrame: Baseline = Day 0 through to Day 58 End of Study Visit
measure: The effectiveness of INI-2004 on Spirometry will be assessed by response to the ragweed allergen challenge (Phase Ib [MAD] only) on Days 23, 37, 51, and 58 compared to baseline (Day 0) via PEF
timeFrame: Baseline = Day 0 through to Day 58
measure: The effectiveness of INI-2004 on Spirometry will be assessed by response to the ragweed allergen challenge (Phase Ib [MAD] only) on Days 23, 37, 51 and 58 compared to baseline (Day 0) Via FEV1
timeFrame: Baseline = Day 0 through to Day 58
measure: The effectiveness of INI-2004 on Spirometry will be assessed by response to the ragweed allergen challenge (Phase Ib [MAD] only) on Days 23, 37, 51 and 58 compared to baseline (Day 0) via FVC
timeFrame: Baseline = Day 0 through to Day 58
measure: The effectiveness of INI-2004 on Spirometry will be assessed by response to the ragweed allergen challenge (Phase Ib [MAD] only) on Days 23, 37, 51 and 58 compared to baseline (Day 0) via FEV1/FVC ratio
timeFrame: Baseline = Day 0 through to Day 58
measure: The effectiveness of INI-2004 on Spirometry will be assessed by response to the ragweed allergen challenge (Phase Ib [MAD] only) on Days 23, 37, 51 and 58 compared to baseline (Day 0) via FEF
timeFrame: Baseline = Day 0 through to Day 58
measure: Single dose PK parameters: maximum observed concentration (Cmax)
timeFrame: Day 1 pre dose, then at 15 and 30 mins post-dose, then 1, 2 and 4 hours post-dose, Day 2 at 24 hours post-dose.
measure: Single dose PK parameters: Time to Cmax (Tmax)
timeFrame: Day 1 pre dose, then at 15 and 30 mins post-dose, then 1, 2 and 4 hours post-dose, Day 2 at 24 hours post-dose.
measure: Single dose PK parameters: Area under the concentration-time curve from time 0 to time t (AUC0-t)
timeFrame: Day 1 pre dose, then at 15 and 30 mins post-dose, then 1, 2 and 4 hours post-dose, Day 2 at 24 hours post-dose.
measure: Single dose PK parameters: Area under the concentration-time curve from time 0 to the last measurable concentration (AUClast)
timeFrame: Day 1 pre dose, then at 15 and 30 mins post-dose, then 1, 2 and 4 hours post-dose, Day 2 at 24 hours post-dose.
measure: Single dose PK parameters: Half-life (t1/2)
timeFrame: Day 1 pre dose, then at 15 and 30 mins post-dose, then 1, 2 and 4 hours post-dose, Day 2 at 24 hours post-dose.
measure: Single dose PK parameters: Clearance (Cl/f)
timeFrame: Day 1 pre dose, then at 15 and 30 mins post-dose, then 1, 2 and 4 hours post-dose, Day 2 at 24 hours post-dose.
measure: Single dose PK parameters: Volume of distribution (Vz/f)
timeFrame: Day 1 pre dose, then at 15 and 30 mins post-dose, then 1, 2 and 4 hours post-dose, Day 2 at 24 hours post-dose.
measure: Single dose PK parameters: Area under the drug concentration-time curve from time zero infinity (AUCinf)
timeFrame: Day 1 pre dose, then at 15 and 30 mins post-dose, then 1, 2 and 4 hours post-dose, Day 2 at 24 hours post-dose.
measure: Multiple dose PK parameters: Drug concentrations from pre-dose to 4 hours post-dose on Days 14 and 35.
timeFrame: Day 14 pre dose then 1, 2 and 4 hours post-dose, Day 35 pre dose then 1, 2 and 4 hours post-dose
measure: Multiple dose PK parameters: AUC0-4 on Days 14 and 35 (if data permits)
timeFrame: Day 14 pre dose then 1, 2 and 4 hours post-dose, Day 35 pre dose then 1, 2 and 4 hours post-dose
measure: Multiple dose PK parameters: Post-dose urine drug concentration on Day 14.
timeFrame: Urine to be collected at 0-2 hours post-dose interval on Day 14 only.
measure: Single dose PD parameters: Changes in cytokine levels in nasal secretions post-dose compared to baseline pre-dose.
timeFrame: Baseline Day 1 pre-dose then 4, 24 and 48 hours post-dose.
measure: Single dose PD parameters: Changes in cytokine levels in plasma post-dose compared to baseline pre-dose.
timeFrame: Baseline Day 1 pre-dose then 4, 24 and 48 hours post-dose.
measure: Multiple dose PD parameters: Changes in concentrations of pro-inflammatory cytokines and nasal mediators in nasal secretions following dose administration compared to baseline pre-dose.
timeFrame: Baseline pre-dose on Day 14 and 35, post-dose Days 14 and 35.
measure: Multiple dose PD parameters: Changes in concentrations of pro-inflammatory cytokines and nasal mediators in plasma following dose administration compared to baseline pre-dose.
timeFrame: Baseline pre-dose on Day 14 and 35, post-dose Days 14 and 35.
Other outcomes:
measure: Multiple dose PD parameters: Changes from baseline of IgG
timeFrame: Day 51 pre ragweed challenge.
measure: Multiple dose PD parameters: Changes from baseline of IgE
timeFrame: Day 51 pre ragweed challenge.
measure: Multiple dose PD parameters: Changes from baseline of IgE/IgG
timeFrame: Day 51 pre ragweed challenge.
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network Pty Ltd
state: Victoria
Study officials:
affiliation: Inimmune Corp
name: JonL. Ruckle
role: STUDY_DIRECTOR
References: