A Phase 1, Randomised, Double-blind, Placebo-Controlled, Single Ascending Dose and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of NP-011 in Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- NP-011 (Single Ascending Dose Phase)
- Conditions
- Myocardial Infarction
- Sponsor
- Nexel Co., Ltd.
- Enrollment
- 64
- Locations
- 1
- Primary Endpoint
- The safety and tolerability of single and multiple doses of NP-011 through the incidence, nature and severity of adverse events
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a Phase 1, randomised, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to evaluate the safety, tolerability, and pharmacokinetic of NP-011 in healthy volunteers.
Detailed Description
NP-011 is a truncated form of human MFG-E8 recombinant protein. NP-011 placebo has an identical formulation to the NP-011 drug product, prepared without the active pharmaceutical ingredient. The study will be conducted in 2 parts: Single Ascending Dose (SAD): The participants will be randomized to receive NP-011 (n= 6 per cohort) or placebo (n= 2 per cohort) on Day 1. For all Part 1 cohorts, 2 sentinel participants will receive the first dose of IP (1 to receive NP-011, 1 to receive placebo) on Day 1. If dosing of the sentinel participants proceeds without clinically significant adverse events over 24 hours, the remaining participants in the cohort will be dosed at the discretion of the Principal Investigator (PI), according to the randomization schedule. There are total five cohorts in Part 1 Cohort 1A: NP-011 250 μg or placebo (6:2) Cohort 1B: NP-011 500 μg or placebo (6:2) Cohort 1C: NP-011 1000 μg or placebo (6:2) Cohort 1D: NP-011 2000 μg or placebo (6:2) Cohort 1E: NP-011 4000 μg or placebo (6:2) Multiple Ascending Dose (MAD): The part 2 progress after the completion of Day 8 assessments in Cohort 1E upon satisfactory review of all available safety data by the SMC. Participants will be enrolled into 3 sequential cohorts in Part 2. Dose levels for Part 2 cohorts may be revised by agreement with the SMC and based on emerging safety and PK data. Cohort 2A: NP-011 1000 μg or placebo (6:2) Cohort 2B: NP-011 2000 μg or placebo (6:2) Cohort 2C: NP-011 4000 μg or placebo (6:2) The participants will be randomized to receive the NP-011 (n= 6 per cohort) or placebo (n=2 per cohort) The safety and pharmacokinetic data will be reviewed by SMC in both the parts (SAD and MAD) prior to the decision to increase or decrease the dose level for the next cohort or expand the number of participants in a cohort (to a maximum of an additional 8 participants at a given dose level).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Normal healthy volunteers with an age of 18 to 65 years inclusive at the time of informed consent.
- •Participants can be of any ethnicity or race, excluding Asian by self-declaration. For the purposes of this protocol, Asian is defined as a person having origins in any of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent, including for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, Philippines, Thailand, and Vietnam. If an individual identifies as mixed race, exclusion will occur if the proportion of self-declaration as Asian exceeds 25%.
- •Participants must be in good general health, in the opinion of the Investigator, with no significant medical history (ie, history of childhood asthma \[resolved\] is acceptable; history of depression \[non-hospitalised, medicated\] or migraines is not acceptable), and no clinically significant abnormalities on physical examination at Screening and/or before administration of the initial dose of IP.
- •Participants must have documented evidence of receipt of licensed COVID-19 vaccinations as per the current Australian Technical Advisory Group on Immunisation (ATAGI) guidelines and be fully vaccinated as per local guidelines.
- •Participants must have a BMI between \> 18.0 and \< 32.0 kg/m2 at Screening.
- •Participants must have clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the Investigator or delegate. A single repeat test can be performed for clinically significant abnormal values, at the discretion of the Investigator.
- •Participants must be a non-smoker and must not have used any tobacco products within 2 months prior to Screening, or if a smoker, they must smoke no more than 2 cigarettes or equivalent per week.
- •Participants must have no relevant dietary restrictions (restrictions that would prevent consumption of the standard meals to be provided), and be willing to consume standard meals provided.
- •Females must be non-pregnant and non-lactating, and must use an acceptable, highly effective double contraception from Screening until 30 days after last dose of IP, including the follow-up period. Double contraception is defined as a condom AND one other form of the following:
- •Established hormonal contraception (with approved oral contraceptive pills \[OCPs\], long-acting implantable hormones, injectable hormones);
Exclusion Criteria
- •Use of any IP or investigational medicinal device within 30 days prior to treatment, or 5 half-lives of the product, whichever is the longest.
- •Prior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the participant or confound treatment assessment.
- •Allergy or hypersensitivity to the IP or any of its constituents.
- •History of allergic or anaphylactic reactions that are considered severe in the opinion of the Investigator (with the allowance of well-managed allergies such as allergic rhinitis, eczema, stinging insect allergies, and pollen allergies).
- •Any history of cardiac disease.
- •Abnormal ECG findings at Screening that are considered by the Investigator to be clinically significant.
- •Use of or anticipated use of any prescription drugs (other than hormonal contraception; OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring, or an IUD), over-the-counter (OTC) medication, herbal remedies, supplements, or vitamins 2 weeks prior to dosing and during course of study without prior approval of the Investigator and MM. Simple analgesics (paracetamol, nonsteroidal anti-inflammatory drugs \[NSAIDs\]) are permitted at 1 or 2 therapeutic doses per week at the discretion of the Investigator.
- •Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.
- •Presence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the participant will comply with the protocol or complete the study per protocol.
- •Blood donation or significant blood loss within 60 days prior to the first IP administration.
Arms & Interventions
Single Ascending Dose Phase
Drug: NP-011 Dosage: 250μg, 500μg, 1000μg, 2000μg, 4000μg Dosage Form: Liquid for IV injection Route of Administration: Intravenous
Intervention: NP-011 (Single Ascending Dose Phase)
Multiple Ascending Dose Phase
Drug: NP-011 Dosage: 1000μg, 2000μg, 4000μg Dosage Form: Liquid for IV injection Route of Administration: Intravenous
Intervention: NP-011 (Multiple Ascending Dose Phase)
Placebo
Dosage Form: Liquid for IV injection Route of Administration: Intravenous
Intervention: NP-011 (Placebo)
Outcomes
Primary Outcomes
The safety and tolerability of single and multiple doses of NP-011 through the incidence, nature and severity of adverse events
Time Frame: Screening to end of the follow up period; up to 36 and 56 days for Single Ascending Dose and Multiple Ascending Dose
Adverse Events will be coded using the most current version of the MedDRA®
Secondary Outcomes
- To characterize the immunogenicity of NP-011 in healthy volunteers by assessing the development of anti-drug-antibodies (ADA) through change from baseline in neutralizing antibody titers for NP-011 after single and multiple doses.(Screening to end of the follow up period; up to 36 and 56 days for Single Ascending Dose and Multiple Ascending Dose)
- To characterize the plasma pharmacokinetics (PK) of NP-011 in healthy volunteers(Screening to end of the follow up period; up to 36 and 56 days for Single Ascending Dose and Multiple Ascending Dose)