Trial of INI-2004 in Healthy Volunteers and Participants With Allergic Rhinitis.
- Conditions
- Allergic Rhinitis Due to Weed PollenAllergic Rhinitis
- Interventions
- Drug: Placebo
- Registration Number
- NCT06038279
- Lead Sponsor
- Inimmune Corporation
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 68
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Healthy Participants will be enrolled and randomised to receive a single dose of INI-2004 or placebo intranasally (ratio 3:1 active: placebo). Arm 3 (SAD)- INI-2004 Dose Cohort 3 INI-2004 Healthy Participants will be enrolled and randomised to receive a single dose of INI-2004 or placebo intranasally (ratio 3:1 active: placebo). Arm 2 (SAD)- INI-2004 Dose Cohort 2 INI-2004 Healthy Participants will be enrolled and randomised to receive a single dose of INI-2004 or placebo intranasally (ratio 3:1 active: placebo). Arm 1 (SAD)- INI-2004 Dose Cohort 1 INI-2004 Healthy Participants will be enrolled and randomised to receive a single dose of INI-2004 or placebo intranasally (ratio 3:1 active: placebo). Arm 4 (SAD)- INI-2004 Dose Cohort 4 INI-2004 Healthy Participants will be enrolled and randomised to receive a single dose of INI-2004 or placebo intranasally (ratio 3:1 active: placebo). Placebo (MAD) Placebo 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. Arm 1 (MAD) - INI-2004 Dose Cohort 1 INI-2004 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. Arm 2 (MAD) -INI-2004 Dose Cohort 2 INI-2004 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. Arm 3 (MAD) - INI-2004 Dose Cohort 3 INI-2004 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.
- Primary Outcome Measures
Name Time Method Change from baseline in 12-lead electrocardiogram parameters after multiple ascending doses (MAD) Baseline = Day 0 through to Day 58 End of Study Visit 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.
Change from baseline in Nasal symptoms after multiple ascending doses (MAD) Baseline = Day 0 through to Day 58 End of Study Visit 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. = severeChange from baseline in Nasal irritancy after a single ascending Dose (SAD) Baseline, Day 1 through to Day 7 End of Study Visit Nasal examination
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) Baseline, Day 1 then daily through to Day 7 End of Study Visit Graded using 5-point scale
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) Baseline = Day 0, Day 14, 21, 28, 35 through to Day 58 End of Study Visit Graded using 5-point scale
Number of Participants with a Change from baseline in Vital signs measurements after a single ascending Dose (SAD) Baseline, Day 1 through to Day 7 End of Study Visit 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.
Change from baseline in 12-lead electrocardiogram parameters after a single ascending Dose (SAD) Baseline, Day 1 through to Day 7 End of Study Visit 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.
Change from baseline in Nasal symptoms after a single ascending Dose (SAD) Baseline, Day 1 through to Day 7 End of Study Visit 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".
Number of Participants with a Change from baseline in Vital signs measurements after multiple ascending doses (MAD) Baseline = Day 0 through to Day 58 End of Study Visit 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.
Number of Participants with a Change from baseline in Clinical laboratory results after multiple ascending doses (MAD) Baseline = Day 0, Day 14 and Day 58 End of Study Visit 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
Change from baseline in Nasal irritancy after multiple ascending doses (MAD) Baseline = Day 0 through to Day 58 End of Study Visit Nasal examination
Change from baseline in Spirometry after a single ascending Dose (SAD) Baseline, Day 1 through to Day 7 End of Study Visit 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.
Change from baseline in Spirometry after multiple ascending doses (MAD) Baseline = Day 0 through to Day 58 End of Study Visit 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.
Number of Participants with a Change from baseline in Clinical laboratory results after a single ascending Dose (SAD) Baseline, Day 2 through to Day 7 End of Study Visit 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
- Secondary Outcome Measures
Name Time Method 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 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.
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 Baseline = Day 0 through to Day 58 FEV1- FEV1 is measured in liters
Single dose PK parameters: Area under the concentration-time curve from time 0 to the last measurable concentration (AUClast) 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. Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose
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 Peak nasal inspiratory flow to be determined using the mean of three replicates.
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 Baseline = Day 0 through to Day 58 FVC is measured in liters
Single dose PK parameters: Time to Cmax (Tmax) 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. Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose
Single dose PK parameters: Area under the concentration-time curve from time 0 to time t (AUC0-t) 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. Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose
Multiple dose PK parameters: AUC0-4 on Days 14 and 35 (if data permits) Day 14 pre dose then 1, 2 and 4 hours post-dose, Day 35 pre dose then 1, 2 and 4 hours post-dose Pharmacokinetics (PK) of INI-2004 in blood plasma following multiple doses
Single dose PK parameters: Clearance (Cl/f) 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. Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose
Multiple dose PD parameters: Changes in concentrations of pro-inflammatory cytokines and nasal mediators in plasma following dose administration compared to baseline pre-dose. Baseline pre-dose on Day 14 and 35, post-dose Days 14 and 35. Pharmacodynamics (PD) of INI-2004 in blood plasma following multiple doses
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 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.
Single dose PK parameters: Half-life (t1/2) 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. Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose
Multiple dose PK parameters: Drug concentrations from pre-dose to 4 hours post-dose on Days 14 and 35. Day 14 pre dose then 1, 2 and 4 hours post-dose, Day 35 pre dose then 1, 2 and 4 hours post-dose Pharmacokinetics (PK) of INI-2004 in blood plasma following multiple doses
Multiple dose PK parameters: Post-dose urine drug concentration on Day 14. Urine to be collected at 0-2 hours post-dose interval on Day 14 only. 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).
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. Baseline pre-dose on Day 14 and 35, post-dose Days 14 and 35. Pharmacodynamics (PD) of INI-2004 in nasal secretions following multiple doses
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 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.
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 PEF- Unit of measurement or PEFis l/min
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 Baseline = Day 0 through to Day 58 FEF 25%-75%- is measured as l/s
Single dose PK parameters: maximum observed concentration (Cmax) 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. Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose
Single dose PK parameters: Volume of distribution (Vz/f) 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. Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose
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 Baseline = Day 0 through to Day 58 FEV1/FVC- is measured in %
Single dose PK parameters: Area under the drug concentration-time curve from time zero infinity (AUCinf) 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. Pharmacokinetics (PK) of INI-2004 in blood plasma following single dose
Single dose PD parameters: Changes in cytokine levels in nasal secretions post-dose compared to baseline pre-dose. Baseline Day 1 pre-dose then 4, 24 and 48 hours post-dose. Pharmacodynamics (PD) of INI-2004 in nasal secretions following single dose
Single dose PD parameters: Changes in cytokine levels in plasma post-dose compared to baseline pre-dose. Baseline Day 1 pre-dose then 4, 24 and 48 hours post-dose. Pharmacodynamics (PD) of INI-2004 in blood plasma following single dose
Trial Locations
- Locations (1)
Nucleus Network Pty Ltd
🇦🇺Melbourne, Victoria, Australia