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).

Study Overview

• Status: Recruiting
• Conditions: Allergic Rhinitis; Allergic Rhinitis Due to Weed Pollen
• Intervention / Treatment: Drug: INI-2004; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Tim Porter; Phone Number: +61 450992172; Email: Tim.Porter@avancecro.com
• Study Contact Backup: Name: Lucinda Tennant; Phone Number: +1 406 451 5913; Email: Lucinda.Tennant@inimmune.com

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Nucleus Network Pty Ltd
      • Principal Investigator: Dr Philip Ryan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 (SAD)- INI-2004 Dose Cohort 1; Healthy Participants will be enrolled and randomised to receive a single dose of INI-2004 or placebo intranasally (ratio 3:1 active: placebo).	Drug: INI-2004; INI-2004 (a toll-like receptor [TLR]4 agonist) liposomal formulation. INI-2004 is an intranasal (IN) TLR4 agonist that is targeted to prevent AR symptoms in subjects with seasonal AR.
Experimental: Arm 2 (SAD)- INI-2004 Dose Cohort 2; Healthy Participants will be enrolled and randomised to receive a single dose of INI-2004 or placebo intranasally (ratio 3:1 active: placebo).	Drug: INI-2004; INI-2004 (a toll-like receptor [TLR]4 agonist) liposomal formulation. INI-2004 is an intranasal (IN) TLR4 agonist that is targeted to prevent AR symptoms in subjects with seasonal AR.
Experimental: Arm 3 (SAD)- INI-2004 Dose Cohort 3; Healthy Participants will be enrolled and randomised to receive a single dose of INI-2004 or placebo intranasally (ratio 3:1 active: placebo).	Drug: INI-2004; INI-2004 (a toll-like receptor [TLR]4 agonist) liposomal formulation. INI-2004 is an intranasal (IN) TLR4 agonist that is targeted to prevent AR symptoms in subjects with seasonal AR.
Experimental: Arm 4 (SAD)- INI-2004 Dose Cohort 4; Healthy Participants will be enrolled and randomised to receive a single dose of INI-2004 or placebo intranasally (ratio 3:1 active: placebo).	Drug: INI-2004; INI-2004 (a toll-like receptor [TLR]4 agonist) liposomal formulation. INI-2004 is an intranasal (IN) TLR4 agonist that is targeted to prevent AR symptoms in subjects with seasonal AR.
Placebo Comparator: Placebo; Healthy Participants will be enrolled and randomised to receive a single dose of INI-2004 or placebo intranasally (ratio 3:1 active: placebo).	Drug: Placebo; The Placebo for INI-2004 is a clear, colorless solution free of particles supplied in 10 mL glass vials with a 10 mL fill.; Other Names: Placebo for INI-2004
Experimental: Arm 1 (MAD) - INI-2004 Dose Cohort 1; Participants with allergic rhinitis will be enrolled and randomised (ratio 3:1 active:placebo) to receive INI-2004 or placebo intranasally once per week for a total of 4 weeks.	Drug: INI-2004; INI-2004 (a toll-like receptor [TLR]4 agonist) liposomal formulation. INI-2004 is an intranasal (IN) TLR4 agonist that is targeted to prevent AR symptoms in subjects with seasonal AR.
Experimental: Arm 2 (MAD) -INI-2004 Dose Cohort 2; Participants with allergic rhinitis will be enrolled and randomised (ratio 3:1 active:placebo) to receive INI-2004 or placebo intranasally once per week for a total of 4 weeks.	Drug: INI-2004; INI-2004 (a toll-like receptor [TLR]4 agonist) liposomal formulation. INI-2004 is an intranasal (IN) TLR4 agonist that is targeted to prevent AR symptoms in subjects with seasonal AR.
Experimental: Arm 3 (MAD) - INI-2004 Dose Cohort 3; Participants with allergic rhinitis will be enrolled and randomised (ratio 3:1 active:placebo) to receive INI-2004 or placebo intranasally once per week for a total of 4 weeks.	Drug: INI-2004; INI-2004 (a toll-like receptor [TLR]4 agonist) liposomal formulation. INI-2004 is an intranasal (IN) TLR4 agonist that is targeted to prevent AR symptoms in subjects with seasonal AR.
Placebo Comparator: Placebo (MAD); Participants with allergic rhinitis will be enrolled and randomised (ratio 3:1 active:placebo) to receive INI-2004 or placebo intranasally once per week for a total of 4 weeks.	Drug: Placebo; The Placebo for INI-2004 is a clear, colorless solution free of particles supplied in 10 mL glass vials with a 10 mL fill.; Other Names: Placebo for INI-2004

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Graded using 5-point scale	Baseline, Day 1 then daily through to Day 7 End of Study Visit
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)	Graded using 5-point scale	Baseline = Day 0, Day 14, 21, 28, 35 through to Day 58 End of Study Visit
Number of Participants with a Change from baseline in Vital signs measurements after a single ascending Dose (SAD)	Pulse rate [PR], systolic and diastolic blood pressure [BP], temperature, respiratory rate.[RR] and oxygen saturation. Blood pressure will be measured using a sphygmomanometer, body temperature will be measured using a thermometer, Heart rate (HR) is measured using vital sign machine, respiratory rate is measured manually via 60-second count and oxygen saturation is measured using a Oximeter. All abnormal assessments measured as Clinically significant post dose will be recorded as AEs.	Baseline, Day 1 through to Day 7 End of Study Visit
Number of Participants with a Change from baseline in Vital signs measurements after multiple ascending doses (MAD)	Pulse rate [PR], systolic and diastolic blood pressure [BP], temperature, respiratory rate.[RR] and oxygen saturation. Blood pressure will be measured using a sphygmomanometer, body temperature will be measured using a thermometer, Heart rate (HR) is measured using vital sign machine,respiratory rate is measured manually via 60-second count.[RR] and oxygen saturation is measured using a Oximeter. All abnormal assessments measured as Clinically significant post dose will be recorded as AEs.	Baseline = Day 0 through to Day 58 End of Study Visit
Change from baseline in 12-lead electrocardiogram parameters after a single ascending Dose (SAD)	12-lead ECGs parameters include but not limited to the measurements of ventricular HR, PR interval, RR interval, QRS duration, QT interval and QTcF. At each protocol scheduled timepoint, ECGs will be performed in triplicate with each replicate separated by at least 1 minute and the full set of triplicates completed within 5 minutes.All Clinically Significant findings post-dose will be recorded as AEs.	Baseline, Day 1 through to Day 7 End of Study Visit
Change from baseline in 12-lead electrocardiogram parameters after multiple ascending doses (MAD)	12-lead ECGs parameters include but not limited to the measurements of ventricular HR, PR interval, RR interval, QRS duration, QT interval and QTcF. At each protocol scheduled timepoint, ECGs will be performed in triplicate with each replicate separated by at least 1 minute and the full set of triplicates completed within 5 minutes.All Clinically Significant findings post-dose will be recorded as AEs.	Baseline = Day 0 through to Day 58 End of Study Visit
Number of Participants with a Change from baseline in Clinical laboratory results after a single ascending Dose (SAD)	Hematology - Blood samples will be collected. All safety laboratory assessments will be assessed by a certified local laboratory, using that laboratory's normal ranges. Any clinically significant changes will be recorded as Adverse events. The severity of each AE and SAE will be graded using a 5-point scale	Baseline, Day 2 through to Day 7 End of Study Visit
Number of Participants with a Change from baseline in Clinical laboratory results after a single ascending Dose (SAD)	Serum chemistry- Blood samples will be collected. All safety laboratory assessments will be assessed by a certified local laboratory, using that laboratory's normal ranges. Any clinically significant changes will be recorded as Adverse event. The severity of each AE and SAE will be graded using a 5-point scale	Baseline, Day 2 through to Day 7 End of Study Visit
Number of Participants with a Change from baseline in Clinical laboratory results after a single ascending Dose (SAD)	Urinalysis- Urine samples will be collected. All safety laboratory assessments will be assessed by a certified local laboratory, using that laboratory's normal ranges. Any clinically significant changes will be recorded as Adverse event. The severity of each AE and SAE will be graded using a 5-point scale	Baseline, Day 2 through to Day 7 End of Study Visit
Number of Participants with a Change from baseline in Clinical laboratory results after multiple ascending doses (MAD)	Hematology - Blood samples will be collected. All safety laboratory assessments will be assessed by a certified local laboratory, using that laboratory's normal ranges. Any clinically significant changes will be recorded as Adverse event. The severity of each AE and SAE will be graded using a 5-point scale	Baseline = Day 0, Day 14 and Day 58 End of Study Visit
Number of Participants with a Change from baseline in Clinical laboratory results after multiple ascending doses (MAD)	Serum chemistry- Blood samples will be collected. All safety laboratory assessments will be assessed by a certified local laboratory, using that laboratory's normal ranges. Any clinically significant changes will be recorded as Adverse event. The severity of each AE and SAE will be graded using a 5-point scale	Baseline = Day 0, Day 14 and Day 58 End of Study Visit
Number of Participants with a Change from baseline in Clinical laboratory results after multiple ascending doses (MAD)	Urinalysis- Urine samples will be collected. All safety laboratory assessments will be assessed by a certified local laboratory, using that laboratory's normal ranges. Any clinically significant changes will be recorded as Adverse event. The severity of each AE and SAE will be graded using a 5-point scale	Baseline = Day 0, Day 14 and Day 58 End of Study Visit
Change from baseline in Nasal symptoms after a single ascending Dose (SAD)	Presence of itching, discomfort, rhinorrhoea, congestion and sneezing are assessed using a 10 cm visual analogue scale [VAS]. The participant will mark on the VAS where they rank their symptoms ranging from "no symptoms" to "worst symptoms ever experienced".	Baseline, Day 1 through to Day 7 End of Study Visit
Change from baseline in Nasal symptoms after multiple ascending doses (MAD)	Presence of itching, discomfort, rhinorrhoea, congestion and sneezing are assessed individually as a Total Nasal Symptoms Score (TNSS) at different time points pre and post-ragweed allergen challenge in the MAD portion of the study. TNSS is the sum of symptoms scores for nasal congestion, rhinorrhoea, nasal itching, and sneezing (each scored on a scale of 0 to 3 (below) with total possible score of 0 to 12. The criterion used to score each symptom is described below: 0 = none: no symptoms; = mild; = moderate; = severe	Baseline = Day 0 through to Day 58 End of Study Visit
Change from baseline in Nasal irritancy after a single ascending Dose (SAD)	Nasal examination	Baseline, Day 1 through to Day 7 End of Study Visit
Change from baseline in Nasal irritancy after multiple ascending doses (MAD)	Nasal examination	Baseline = Day 0 through to Day 58 End of Study Visit
Change from baseline in Spirometry after a single ascending Dose (SAD)	Peak expiratory flow [PEF]-Pulmonary function will be assessed using a handheld spirometer at the time points indicated. A minimum of 3 readings should be completed and recorded at each time point. Observed values and changes from baseline for PEF will be summarised at each scheduled time point using descriptive statistics. Unit of measurement used for PEF is l/min.	Baseline, Day 1 through to Day 7 End of Study Visit
Change from baseline in Spirometry after a single ascending Dose (SAD)	Forced expiratory volume in 1 second [FEV1]- Pulmonary function will be assessed using a handheld spirometer at the time points indicated. A minimum of 3 readings should be completed and recorded at each time point. Observed values and changes from baseline for FEV1 will be summarised at each scheduled time point using descriptive statistics. Unit of measurement used for FEV1 is liters.	Baseline, Day 1 through to Day 7 End of Study Visit
Change from baseline in Spirometry after a single ascending Dose (SAD)	Forced vital capacity [FVC]- Pulmonary function will be assessed using a handheld spirometer at the time points indicated. A minimum of 3 readings should be completed and recorded at each time point. Observed values and changes from baseline for FVC will be summarised at each scheduled time point using descriptive statistics. Units of measurement used for FVC is liters.	Baseline, Day 1 through to Day 7 End of Study Visit
Change from baseline in Spirometry after a single ascending Dose (SAD)	Forced expiratory flow over the middle one-half of the FVC [FEF25-75%]- Pulmonary function will be assessed using a handheld spirometer at the time points indicated. A minimum of 3 readings should be completed and recorded at each time point. Observed values and changes from baseline for spirometry assessments FEF25-75% will be summarised at each scheduled time point using descriptive statistics. Unit of measurement used for FEV1/FVC is %.	Baseline, Day 1 through to Day 7 End of Study Visit
Change from baseline in Spirometry after a single ascending Dose (SAD)	FEV1/FVC ratio- Pulmonary function will be assessed using a handheld spirometer at the time points indicated. A minimum of 3 readings should be completed and recorded at each time point. Observed values and changes from baseline for spirometry assessments FEV1/FVC ratio will be summarised at each scheduled time point using descriptive statistics. Unit of measurement used for FEF 25%-75% is l/s.	Baseline, Day 1 through to Day 7 End of Study Visit
Change from baseline in Spirometry after multiple ascending doses (MAD)	Peak expiratory flow [PEF]- Pulmonary function will be assessed using a handheld spirometer at the time points indicated. A minimum of 3 readings should be completed and recorded at each time point. Observed values and changes from baseline for PEF will be summarised at each scheduled time point using descriptive statistics. Unit of measurement used for PEF is l/min.	Baseline = Day 0 through to Day 58 End of Study Visit
Change from baseline in Spirometry after multiple ascending doses (MAD)	Forced expiratory volume in 1 second [FEV1]- Pulmonary function will be assessed using a handheld spirometer at the time points indicated. A minimum of 3 readings should be completed and recorded at each time point. Observed values and changes from baseline for FEV1 will be summarised at each scheduled time point using descriptive statistics. Unit of measurement used for FEV1 is liters.	Baseline = Day 0 through to Day 58 End of Study Visit
Change from baseline in Spirometry after multiple ascending doses (MAD)	Forced vital capacity [FVC]- Pulmonary function will be assessed using a handheld spirometer at the time points indicated. A minimum of 3 readings should be completed and recorded at each time point. Observed values and changes from baseline for FVC will be summarised at each scheduled time point using descriptive statistics. Units of measurement used for FVC is liters.	Baseline = Day 0 through to Day 58 End of Study Visit
Change from baseline in Spirometry after multiple ascending doses (MAD)	FEF25-75% - Pulmonary function will be assessed using a handheld spirometer at the time points indicated. A minimum of 3 readings should be completed and recorded at each time point. Observed values and changes from baseline for FEF25-75%, will be summarised at each scheduled time point using descriptive statistics. Unit of measurement used for FEV1/FVC is %.	Baseline = Day 0 through to Day 58 End of Study Visit
Change from baseline in Spirometry after multiple ascending doses (MAD)	FEV1/FVC ratio- Pulmonary function will be assessed using a handheld spirometer at the time points indicated. A minimum of 3 readings should be completed and recorded at each time point. Observed values and changes from baseline for FEV1/FVC ratio will be summarised at each scheduled time point using descriptive statistics. Unit of measurement used for FEF 25%-75% is l/s.	Baseline = Day 0 through to Day 58 End of Study Visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Determined by acoustic rhinometry. Acoustic rhinometry will be performed using GM Instruments. Measurements to include (at a minimum) nasal volume and cross-sectional area. Measurements will be performed for both left and right nasal cavities independently.	Baseline = Day 0 through to Day 58
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)	Peak nasal inspiratory flow to be determined using the mean of three replicates.	Baseline = Day 0 through to Day 58
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)	Total nasal symptom score [TNSS] will be measured on a scale of 0 to 3 with a total possible score of 0 to 12. 0= none, no symptoms, 1= mild, 2= moderate, 3=severe.	Baseline = Day 0 through to Day 58
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)	Nasal examination- A macroscopic nasal examination will be performed, including conventional anterior rhinoscopy using an otoscope with an attached otic speculum (or nasal speculum and headlight) to assess swelling of the mucosa, erythema, and secretions. All post-dose CS events will be recorded as AEs.	Baseline = Day 0 through to Day 58 End of Study Visit
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	PEF- Unit of measurement or PEFis l/min	Baseline = Day 0 through to Day 58
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	FEV1- FEV1 is measured in liters	Baseline = Day 0 through to Day 58
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	FVC is measured in liters	Baseline = Day 0 through to Day 58
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	FEV1/FVC- is measured in %	Baseline = Day 0 through to Day 58
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	FEF 25%-75%- is measured as l/s	Baseline = Day 0 through to Day 58
Single dose PK parameters: maximum observed concentration (Cmax)	Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose	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.
Single dose PK parameters: Time to Cmax (Tmax)	Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose	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.
Single dose PK parameters: Area under the concentration-time curve from time 0 to time t (AUC0-t)	Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose	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.
Single dose PK parameters: Area under the concentration-time curve from time 0 to the last measurable concentration (AUClast)	Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose	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.
Single dose PK parameters: Half-life (t1/2)	Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose	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.
Single dose PK parameters: Clearance (Cl/f)	Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose	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.
Single dose PK parameters: Volume of distribution (Vz/f)	Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose	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.
Single dose PK parameters: Area under the drug concentration-time curve from time zero infinity (AUCinf)	Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose	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.
Multiple dose PK parameters: Drug concentrations from pre-dose to 4 hours post-dose on Days 14 and 35.	Pharmacokinetics (PK) of INI-2004 in blood plasma following multiple doses	Day 14 pre dose then 1, 2 and 4 hours post-dose, Day 35 pre dose then 1, 2 and 4 hours post-dose
Multiple dose PK parameters: AUC0-4 on Days 14 and 35 (if data permits)	Pharmacokinetics (PK) of INI-2004 in blood plasma following multiple doses	Day 14 pre dose then 1, 2 and 4 hours post-dose, Day 35 pre dose then 1, 2 and 4 hours post-dose
Multiple dose PK parameters: Post-dose urine drug concentration on Day 14.	Pharmacokinetics (PK) of INI-2004 in urine following multiple doses - decision if endpoint will be evaluated will be determined following review of plasma PK data from Phase I (SAD).	Urine to be collected at 0-2 hours post-dose interval on Day 14 only.
Single dose PD parameters: Changes in cytokine levels in nasal secretions post-dose compared to baseline pre-dose.	Pharmacodynamics (PD) of INI-2004 in nasal secretions following single dose	Baseline Day 1 pre-dose then 4, 24 and 48 hours post-dose.
Single dose PD parameters: Changes in cytokine levels in plasma post-dose compared to baseline pre-dose.	Pharmacodynamics (PD) of INI-2004 in blood plasma following single dose	Baseline Day 1 pre-dose then 4, 24 and 48 hours post-dose.
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.	Pharmacodynamics (PD) of INI-2004 in nasal secretions following multiple doses	Baseline pre-dose on Day 14 and 35, post-dose Days 14 and 35.
Multiple dose PD parameters: Changes in concentrations of pro-inflammatory cytokines and nasal mediators in plasma following dose administration compared to baseline pre-dose.	Pharmacodynamics (PD) of INI-2004 in blood plasma following multiple doses	Baseline pre-dose on Day 14 and 35, post-dose Days 14 and 35.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple dose PD parameters: Changes from baseline of IgG	Effects of INI-2004 in blood serum on ragweed-specific immunoglobulins following multiple doses.	Day 51 pre ragweed challenge.
Multiple dose PD parameters: Changes from baseline of IgE	Effects of INI-2004 in blood serum on ragweed-specific immunoglobulins following multiple	Day 51 pre ragweed challenge.
Multiple dose PD parameters: Changes from baseline of IgE/IgG	Effects of INI-2004 in blood serum on ragweed-specific immunoglobulins following multiple	Day 51 pre ragweed challenge.

Collaborators and Investigators

• Sponsor: Inimmune Corporation
• Collaborators: Avance Clinical Pty Ltd.
• Investigators: Study Director: JonL. Ruckle, Inimmune Corp

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: July 31, 2023
• First Submitted That Met QC Criteria: September 7, 2023
• First Posted (Actual): September 14, 2023

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic
• Other Study ID Numbers: INI-2004-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No