KP001 for Safety Evaluation

Overseen By Bruno Francoeur, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Kokua Pharma Inc.

Must not be taking: MAO inhibitors

Disqualifiers: Drug abuse, Alcohol abuse, Anaphylaxis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 5 weeks

16 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to evaluate the safety, tolerability, and pharmacokinetics (PK) of several KP001 dose regimens to identify a treatment regimen with a PK profile that safely meets or exceeds the PK profile of existing injected epinephrine products. The main questions it aims to answer are: * To evaluate any carryover effect with a 7-day washout of different dose regimens of KP001 in healthy adult volunteers. * To evaluate the safety, tolerability and PK of different dose regimens of KP001 in healthy adult volunteers. * To explore the safety, tolerability and PK of one KP001 dose regimen without inhalation (breath holding). Participants will: * Be admitted to clinical research unit (Day -1) and receive treatment the following day (Day 1) and then will be discharged * Visit the clinic on Days 2 \& 3 post dose for required assessments * Visit the clinic 6 days post their last dose for dosing and repeated until 5 dosing visits have been completed * Visit the clinic for a safety follow-up visit approximately 1 week from last dose administered

Will I have to stop taking my current medications?

Yes, you will need to stop taking any prescription medications 14 days before joining the trial and any over-the-counter medications 7 days before, except for occasional use of acetaminophen (up to 2 grams daily).

What safety data exists for KP001 or similar treatments?

The research articles provided do not contain specific safety data for KP001 or similar treatments. ^{1 2 3 4 5}

Research Team

Bruno Francoeur, MD

Principal Investigator

Syneos HealthClinique Inc.

Eligibility Criteria

This trial is for healthy adults who can participate in a study to test KP001, a potential new treatment for severe allergic reactions. Participants will need to stay at the research unit overnight and visit the clinic multiple times. Specific eligibility criteria are not provided.

Inclusion Criteria

Demonstrated ability to successfully complete pressurized metered dose inhaler (pMDI) training

My lung function tests are normal.

My BMI is between 18.5 and 30, and my weight is over 50 kg if male, or over 45 kg if female.

Exclusion Criteria

Positive urine drug screen, urine cotinine test, or alcohol breath test, at screening

Known reaction or sensitivity to sympathomimetic amines, or idiosyncratic reaction to epinephrine or any of the ingredients of KP001, placebo

History of anaphylaxis or other severe allergic reactions (e.g., angioedema)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 6 weeks

Treatment

Participants receive various doses of KP001 or placebo in a crossover design to evaluate safety, tolerability, and pharmacokinetics

5 weeks

5 in-patient dosing visits, separated by 1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 safety follow-up visit approximately 1 week from last dose administered

Treatment Details

Interventions

• KP001

Trial Overview KP001, which might be an alternative to injected epinephrine for severe allergies, is being tested against a placebo. The study looks at how safe it is and how the body processes it with different dosing schedules, including one without inhalation.

Participant Groups

Group I: Treatment Arm C: Breath Hold Experimental Treatment 2 Interventions

Subjects will receive 0.5 mg of KP001 (or matching placebo) delivered as 4 rapidly administered sequential inhalations (4 total), dosed approximately 5 seconds apart, spaced over approximately 15 seconds while holding their breath during the entire dosing treatment and after treatment for a total minimum 30 seconds (or longer) before exhaling. Total dose in mg for Arm = 0.5 mg.

Group II: Treatment Arm B: Four Treatments Experimental Treatment 2 Interventions

Subjects will receive four sets of treatments of 0.25 mg (2 inhalations of 0.125 mg each time), totaling 1.0mg of KP001 (or matching placebo) over 2 visits separated by a 1-week washout period. IP will be delivered as 4 sets of 2 inhalations (8 total) spaced approximately 10 seconds apart. Each set of 2 inhalations will be spaced approximately 2 minutes apart. Subjects will repeat Arm therefore total dose in mg for Arm = 2.0 mg.

Group III: Treatment Arm A: Two Treatments Experimental Treatment 2 Interventions

Subjects will receive two sets of treatments of 0.25 mg (2 inhalations of 0.125 mg each time) of KP001 (or matching placebo) over 2 visits separated by a 1-week washout period. Investigational Product (IP) will be delivered as 1 set of 2 inhalations (2 total) spaced approximately 10 seconds apart. Subjects will repeat Arm therefore total dose in mg for Arm = 0.5 mg.

Who Is Running the Clinical Trial?

Kokua Pharma Inc.

Lead Sponsor

Findings from Research

In a clinical development program involving 1684 subjects and 2038 injections, OptiMARK demonstrated a safety profile comparable to Magnevist, with 31% of its injections associated with adverse events.

OptiMARK was found to be safe and well-tolerated, showing fewer adverse events compared to Magnevist (35%) and placebo (48%), indicating its potential as a reliable imaging agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The OptiMARK clinical development program: summary of safety data. Brown, JJ., Kristy, RM., Stevens, GR., et al.[2019]

The recent fatal adverse event in the BIA-102474-101 clinical trial highlights significant limitations in the current safety review process for first-into-human trials, despite previous trials with similar compounds being conducted without incident.

To improve safety in future trials, it is crucial to implement sequential dosing strategies, thorough reviews of preclinical toxicity studies, and systematic risk assessments, especially for novel compounds that may pose higher risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of the BIA-102474-101 study for review of first-into-human clinical trials. Eddleston, M., Cohen, AF., Webb, DJ.[2021]

The University of Connecticut developed a customized online system for tracking and reviewing adverse events in clinical research, which allows for efficient classification and timely reporting of serious incidents.

In the previous academic year, the system reviewed 371 serious adverse events from over 900 studies, demonstrating its effectiveness in ensuring participant safety and providing recommendations for study modifications or suspensions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic identification and classification of adverse events in human research. Silverman, DI., Cirullo, L., DeMartinis, NA., et al.[2006]

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

The first-in-human clinical trial of BIA 10-2474 resulted in serious adverse events for 6 healthy volunteers, including 1 death, highlighting the heightened risks associated with novel investigational drugs transitioning from animal studies to human trials.

The symposium emphasized the need for careful planning and communication in clinical trials to minimize risks to participants, suggesting that a complex matrix of factors must be considered to ensure safety and integrity in first-in-human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety in FIH Trials: A Summary of the Symposium "Fatal Drug Trial in Phase 1: Understanding Risk, Subject Safety, Timelines, and Cost". Greenberg, HE., van Iersel, MT., Westrick, ML., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

The OptiMARK clinical development program: summary of safety data. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Implications of the BIA-102474-101 study for review of first-into-human clinical trials. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Systematic identification and classification of adverse events in human research. [2006]

4. United States pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Safety in FIH Trials: A Summary of the Symposium "Fatal Drug Trial in Phase 1: Understanding Risk, Subject Safety, Timelines, and Cost". [2020]