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Trial registered on ANZCTR


Registration number
ACTRN12622001027707
Ethics application status
Approved
Date submitted
15/06/2022
Date registered
22/07/2022
Date last updated
26/05/2023
Date data sharing statement initially provided
22/07/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study to evaluate the pharmacokinetic, safety and tolerability of NP-201 acetate injection in healthy adult volunteers
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Single-Dose, Phase 1 Clinical Study To Evaluate The Pharmacokinetic Characteristics, Safety, And Tolerability After Subcutaneous Administration Of Np-201 Acetate Injection In Healthy Adult Volunteers
Secondary ID [1] 307319 0
NIB-IND-319ACSP
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary fibrosis 326608 0
Condition category
Condition code
Oral and Gastrointestinal 327035 327035 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigational Product (IP): NP-201 acetate injection
Route of Administration: subcutaneous injection
Dosage and frequency:
Dosing group 1: 100 mg of NP-201 acetate administered once on Day 1
Dosing group 2: 200 mg of NP-201 acetate administered once on Day 1
Dosing group 3: 300 mg of NP-201 acetate administered once on Day 1
Dosing group 4: 400 mg of NP-201 acetate administered once on Day 1
The participants will be randomized across 4 sequential treatment dose groups to receive either the NP-201 acetate or the placebo in each dosing group. There is total 4 dosing group. Each dose group will enrol 8 participants and will be divided into 2 blocks to implement the sentinel dosing approach. The first block in each dose group consists of 2 sentinel participants; 1 participant will receive NP-201 acetate and the other will receive the placebo-to-match. The second block will consist of the remaining 6 participants, who will be randomized to receive either NP-201 acetate (n = 5) or the placebo-to-match (n = 1).
The participants are required to fast for at least 10 hours and restrict the intake of water for 1 hour prior to administration.
The IP will be administered by appropriately trained study staff under the supervision of Investigator. The dose administered, and the time of administration (time of start of the injection) will be checked and recorded.
Each dosing group will enrol distinct group of participants.
Dosing groups will begin after safety assessment of the previous cohort has been completed, all dosing groups will run one after the other.
Intervention code [1] 323764 0
Treatment: Drugs
Comparator / control treatment
The placebo contains potassium phosphate monobasic and sodium phosphate dibasic anhydrous (drug product without NP-201 Acetate).
Control group
Placebo

Outcomes
Primary outcome [1] 331666 0
Safety and tolerability of the single subcutaneous (SC) administration of NP 201 acetate in healthy adult volunteers through incidence of adverse events (AEs) will be graded by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Timepoint [1] 331666 0
Once daily from Baseline to Day 29 post dose administration
Primary outcome [2] 331667 0
Evaluate the pharmacokinetics (PK) profile of the single SC administration of NP-201 acetate in healthy adult volunteers
Blood and urine sample will be collected for PK evaluation.
Parameters:
- Maximum concentration (Cmax)
- Time to maximum concentration (Tmax)
- Area under the drug concentration-time curve, from time zero to the last measurable concentration (AUC(0-last))
- Area under the drug concentration-time curve, from time zero to infinity (AUC0-inf)
- Apparent terminal half-life
- Apparent clearance (CL/F)
- Apparent terminal volume of distribution (Vz/F)
- Mean residence time (MRTlast)
- Renal clearance (CLR)
- Amount of parent drug or its metabolites excreted in urine (Ae)
Timepoint [2] 331667 0
Time points for PK blood sampling times: Pre dose on Day 1 (within one hour prior to dosing), post dose 5 minutes (0.083 hours), 10 minutes (0.167 hours), 20 minutes (0.333 hours), 30 minutes (0.5 hours), 40 minutes (0.667 hours), 50 minutes (0.833 hours), 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours (Day 2)

Timepoints for PK urine sampling: Predose on Day 1, post dose between 0.5 to 4 hours, 4.5 to 8 hours, 8.5 to 12 hours, 12 to 24 hours

Secondary outcome [1] 410689 0
Evaluate associations between various biomarkers (genomic, proteomic, and metabolomic) for pharmacodynamic (PD) measures.
1. Blood (serum) samples will be collected for metabolomics and proteomics analysis during the study
2. DNA sampling for genomic analyses: DNA will be collected from a blood sample.
Timepoint [1] 410689 0
Metabolomics and proteomics analysis on Day 2 post dose administration
DNA sampling for genomic analysis will be performed at Screening Visit.
Secondary outcome [2] 410690 0
To evaluate the immunogenicity of NP-201 acetate through the presence of anti-drug antibody (ADA).
Timepoint [2] 410690 0
Immunogenicity assessments (ADA) will be performed at Baseline (Day -1) and Day 29 post dose administration.
Immunogenicity assessments (ADA) will be assessed in blood serum samples.

Eligibility
Key inclusion criteria
1) Healthy males and females, between 18 to 60 years inclusive, at the time of Screening.
2) Body mass index (BMI) between 18 kg/m2 and less than 32 kg/m2 at Screening, with a minimum body weight of 50 kg and a maximum body weight of 100 kg (inclusive).
3) In good health based on the results of medical history, physical examinations, 12-lead ECG, vital signs measurement, and clinical laboratory evaluations at Screening as assessed by the PI or designee.
4) Participants whose smoking habit in the last 3 months prior to Screening included no more than 14 cigarettes per week (includes e-cigarettes and other nicotine and tobacco products) can be included in the study but must be willing to abstain from smoking from Screening until completion of the EOS visit.
5) Participants who are able to receive SC injections.
6) All female participants of childbearing potential with male partners and male participants with female partners of childbearing potential must consent to use 2 highly effective methods of contraception from start of study and for at least 90 days following the EOS visit or last dose of study treatment, whichever is later. WOCBP on hormonal contraceptives must be stable on the medication for at least 2 menstrual cycles prior to Day -1.
The following are acceptable methods of highly effective contraception:
a. Using twice the normal protection of birth control by using a condom AND one other form of contraception; either birth control pills (The Pill), or injectable birth control, birth control patch or contraceptive implant associated with inhibition of ovulation, or intrauterine device; or
b. Surgical sterilization as a single form of birth control: i.e., tubal ligation, hysterectomy, bilateral oophorectomy, vasectomy, or equivalently effective surgical form of birth control (with documented proof of the absence of sperm in the post-vasectomy ejaculate) at least 6 months prior to Screening; or
c. True sexual abstinence for the duration of the study and for at least 12 weeks following the EOS visit or after the last dose of IP, whichever is later, is acceptable only when in line with the preferred and usual lifestyle of the participant.
Periodic abstinence (calendar, symptothermal, post ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea methods are not considered “true” abstinence and are not acceptable methods of contraception.
Male participants must refrain from sperm donation from start of study and for 90 days after last dose of IP; female participants must refrain from donation of ova from start of study and for 120 days after last dose of IP.
WOCBP must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1, and be willing to undergo additional pregnancy tests, as required, throughout the study. If a participant’s pregnancy test is positive, they will be referred to their primary care provider for follow up; they will not be enrolled in the study.
Women not of childbearing potential must be postmenopausal (defined as cessation of regular menstrual periods for at least 12 months without an alternative medical cause), confirmed by follicle-stimulating hormone (FSH) level greater than 40 IU/mL at Screening.
Female or male participants who are exclusively in same-sex relationships as their preferred and usual lifestyle are not required to use contraception.
7) Ability and willingness to restrict the use of alcohol to equal to 21 units per week for males and equal to 14 units per week for females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits. Participants must have negative alcohol breath tests at Screening and Day -1 visits.
8) Participants must participate voluntarily, sign the informed consent form (ICF), have good compliance, be able and willing to attend the necessary site visits and be willing to cooperate with follow-up visits.
9) Participants must refrain from intensive exercise during the study.
10) Participants should be fully vaccinated (3 doses of an approved vaccine) against SARS CoV 2 at least 2 weeks prior to the Screening visit.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Have a clinically significant medical history or surgical history and have at least 1 of the following findings:
a) Have skin diseases that may affect the absorption of the IP (eg, psoriasis, contact dermatitis), scars and skin abnormalities that may interfere with SC injections, or a history of surgery within 60 days of Screening (except for simple appendectomy or hernia repair, as assessed by the PI or designee).
b) Have a recent significant history of kidney diseases, pancreatitis and/ or urinary stones.
c) Have a recent significant history of lung diseases and/or asthma or pneumonia.
d) Have tested positive during Screening for SARS-CoV-2 viral infection.
e) Have known clinically significant allergies as assessed by the PI or designee, diseases of either/or the cardiovascular system, peripheral vascular system, skin, mucous membranes, eyes, respiratory system, musculoskeletal system, and any other diseases that may pose a problem with the PK evaluation. History of childhood asthma can be included at the discretion of the PI or designee.
2) Pregnant or lactating at Screening or planning to become pregnant at any time during the study, including the follow-up period.
3) Have history of bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
4) Have a history of hypersensitivity reactions or allergic reactions to drugs containing NP 201 or ingredients in the same class, or other drugs (such as aspirin and antibiotics), or known drug allergies (e.g., to aspirin, non-steroidal anti-inflammatory drugs [NSAIDs], antibiotics, iodine, anesthetics, other monoclonal antibodies, etc.).
5) Participants who have donated whole blood within 60 days prior to Screening or blood components within 30 days or received blood transfusion within 60 days.
6) Have received an IP or bioequivalence IP in another clinical study or bioequivalence study within 30 days prior to Screening or five half-lives prior to Screening.
7) Use of any prescription drugs or non-prescription medications/products, including vitamins, minerals, and phyto-therapeutic/herbal/plant-derived preparations, oriental medicines, or dietary supplements within 14 days prior to Screening or over-the-counter drugs within 7 days. The occasional use of paracetamol (up to 2g/day) is permitted.
8) History of alcoholism, substance or drug abuse-related disorders deemed significant by the PI or designee.
9) Participants with a positive toxicology screening panel (urine test including qualitative identification of barbiturates, morphine, cocaine, tetrahydrocannabinol [THC], amphetamines and methamphetamines, benzodiazepines, tricyclic antidepressants [TCAs], methadone, and phencyclidine).
10) Have positive serology test (hepatitis B surface antigen [HBsAg], or hepatitis C virus antibody [anti-HCV], human immunodeficiency virus [HIV] test, syphilis test) at Screening.
11) Active infection requiring medical treatment and/or isolation.
12) Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST) more than 2.0 × upper limit of normal (ULN).
13) Bilirubin more than 1.5 × ULN (isolated bilirubin greater than 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percentage).
14) QTc more than 450 msec for male participants or QTc more than 470 msec for female participants. The QTc is the QT interval corrected for heart rate according to Fridericia’s formula (QTcF).
15) Participants with greater than ULN of calcium (Ca), uric acid, and/or less than or equal to lower limit of normal (LLN) of less than 90 mL/min calculated using Cockroft and Gault formula.
16) Presence of any underlying physical, or psychological medical condition that, in the opinion of the PI or designee, will make it unlikely that the participant will comply with the protocol, or complete the study per the protocol.
17) Participants with tattoos, scars, and/or sites with bruises and redness that cover the abdomen.
18) Others who are ineligible to participate in this clinical study as determined by the PI or designee.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation will be done using the randomisation schedule produced and provided by Novotech.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A randomization list will be prepared using a statistical software package by a Biostatistician
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
25/07/2022
Actual
14/09/2022
Date of last participant enrolment
Anticipated
28/08/2022
Actual
24/01/2023
Date of last data collection
Anticipated
14/12/2022
Actual
22/02/2023
Sample size
Target
32
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 22527 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 37766 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 311612 0
Commercial sector/Industry
Name [1] 311612 0
NIBEC Co., Ltd
Country [1] 311612 0
Korea, Republic Of
Primary sponsor type
Commercial sector/Industry
Name
NIBEC Co., Ltd
Address
Changgyeong Building, 10th floor, 174, Yulgok-ro, Jongno-gu, Seoul, 03127
Country
Korea, Republic Of
Secondary sponsor category [1] 313045 0
None
Name [1] 313045 0
Address [1] 313045 0
Country [1] 313045 0
Other collaborator category [1] 282329 0
Commercial sector/Industry
Name [1] 282329 0
Novotech (Australia) Pty Limited
Address [1] 282329 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 282329 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311054 0
Bellberry HREC
Ethics committee address [1] 311054 0
Ethics committee country [1] 311054 0
Australia
Date submitted for ethics approval [1] 311054 0
08/06/2022
Approval date [1] 311054 0
22/07/2022
Ethics approval number [1] 311054 0
2022-05-458

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 119834 0
Dr Nicholas Farinola
Address 119834 0
CMAX Clinical Research Pty Ltd,
Level 5, 18a North Terrace Adelaide SA 5000
Country 119834 0
Australia
Phone 119834 0
+61 870887900
Fax 119834 0
Email 119834 0
[email protected]
Contact person for public queries
Name 119835 0
Nicholas Farinola
Address 119835 0
CMAX Clinical Research Pty Ltd,
Level 5, 18a North Terrace Adelaide SA 5000
Country 119835 0
Australia
Phone 119835 0
+61 870887900
Fax 119835 0
Email 119835 0
[email protected]
Contact person for scientific queries
Name 119836 0
Nicholas Farinola
Address 119836 0
CMAX Clinical Research Pty Ltd,
Level 5, 18a North Terrace Adelaide SA 5000
Country 119836 0
Australia
Phone 119836 0
+61 870887900
Fax 119836 0
Email 119836 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.