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

NCT06038279 | Completed Phase 1 FDA Drug

• 1 other identifier: INI-2004-101
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

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).

Conditions

Allergic Rhinitis Due to Weed Pollen; Allergic Rhinitis

Outcome Measures

Primary Outcomes (26)

• 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 1. = mild 2. = moderate 3. = 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 Outcomes (24)

• 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)

  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)

  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)

  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)

  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

  Baseline = Day 0 through to Day 58

Other Outcomes (3)

• Multiple dose PD parameters: Changes from baseline of IgG

  Day 51 pre ragweed challenge.

• Multiple dose PD parameters: Changes from baseline of IgE

  Day 51 pre ragweed challenge.

• Multiple dose PD parameters: Changes from baseline of IgE/IgG

  Day 51 pre ragweed challenge.

Study Arms (9)

Arm 1 (SAD)- INI-2004 Dose Cohort 1

EXPERIMENTAL

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

Arm 2 (SAD)- INI-2004 Dose Cohort 2

EXPERIMENTAL

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

Arm 3 (SAD)- INI-2004 Dose Cohort 3

EXPERIMENTAL

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

Arm 4 (SAD)- INI-2004 Dose Cohort 4

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Arm 1 (MAD) - INI-2004 Dose Cohort 1

EXPERIMENTAL

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

Arm 2 (MAD) -INI-2004 Dose Cohort 2

EXPERIMENTAL

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

Arm 3 (MAD) - INI-2004 Dose Cohort 3

EXPERIMENTAL

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

Placebo (MAD)

PLACEBO COMPARATOR

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

Interventions

INI-2004 DRUG

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.

Arm 1 (MAD) - INI-2004 Dose Cohort 1; Arm 1 (SAD)- INI-2004 Dose Cohort 1; Arm 2 (MAD) -INI-2004 Dose Cohort 2; Arm 2 (SAD)- INI-2004 Dose Cohort 2; Arm 3 (MAD) - INI-2004 Dose Cohort 3; Arm 3 (SAD)- INI-2004 Dose Cohort 3; Arm 4 (SAD)- INI-2004 Dose Cohort 4

Placebo DRUG

The Placebo for INI-2004 is a clear, colorless solution free of particles supplied in 10 mL glass vials with a 10 mL fill.

Also known as: Placebo for INI-2004

Placebo; Placebo (MAD)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Female participants must be of non-child-bearing potential i.e., surgically sterilised at least 6 weeks before the screening visit or postmenopausal.
• 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.
• Participant is willing to refrain from consuming food or beverages containing caffeine, within 24 hours prior to each clinic visit.
• Female participants must be of non-child-bearing potential i.e., surgically sterilised or postmenopausal.

You may not qualify if:

• Hypersensitivity or other clinically significant reaction to the study drug or its active ingredients.
• 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.
• 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.
• History of recurrent migraine headaches within 4 weeks prior to screening.
• Positive alcohol breath, urine test, HBsAg, HepC virus antibody, or HIV antibody tests.
• Participant has donated blood or blood products within 3 months prior to first dose administration.
• Use of tobacco products or nicotine-containing products (including smoking cessation aids such as gum or patches.
• Participant plans to travel to an area with known environmental ragweed exposures at any time during study participation.

Sponsors & Collaborators

• Inimmune Corporation: lead
• Avance Clinical Pty Ltd.: collaborator

Study Sites (1)

Nucleus Network Pty Ltd

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Rhinitis, Allergic

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• JonL. Ruckle

  Inimmune Corp

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study. Blinding of active/placebo assignment is critical to the integrity of this clinical study. Those blinded to study drug assignment include the Sponsor, the PI (or delegate), clinical study personnel participating in participants' care or clinical evaluations, the CRO project team (with exceptions noted below) and the study participants. INI-2004 and placebo will be administered to the participant in a manner to ensure treatment assignment remains blinded. Blinded data will be provided to the SRC so as not to reveal treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: September 14, 2023
• Study Start: July 4, 2023
• Primary Completion: September 5, 2024
• Study Completion: September 5, 2024
• Last Updated: January 16, 2026

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)