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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03189017




Registration number
NCT03189017
Ethics application status
Date submitted
12/06/2017
Date registered
16/06/2017
Date last updated
1/08/2019

Titles & IDs
Public title
A Phase I Study of ICP-022 in Healthy Subjects
Scientific title
A Phase I Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Trial in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ICP-022 Following Single and Multiple Escalating Dose
Secondary ID [1] 0 0
ICP-CL-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Lupus Erythematosus 0 0
Rheumatoid Arthritis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ICP-022
Treatment: Drugs - Placebos

Experimental: ICP-022 - There are 5 cohorts in the Part 1 phase of the trial. Three quarters of subjects will be randomized to receive ICP-022 in a double-blind fashion. Five dose levels will be evaluated; dose escalation steps may be modified based on the safety from the previous dose. Cohort 4 will return on Day 8 and receive a single dose of ICP-022 under fed conditions.
In Part 2 phase of the trial,three quarters of subjects will be randomized to receive the ICP-022 in a double-blind fashion in 3 cohorts. ICP-022 will be administered once a day for 14 consecutive days.

Placebo Comparator: Placebos - In part 1 phase of the trial, one quarter of subjects will be randomized to receive placebo in a double-blind fashion. Cohort 4 will return on Day 8 and receive a single dose of placebo under fed conditions.
In Part 2 phase of the trial,one quarter of subjects will be randomized to receive placebo in a double-blind fashion. Placebo will be administered once a day for 14 consecutive days.


Treatment: Drugs: ICP-022
The drug product is a white, round, uncoated tablet.

Treatment: Drugs: Placebos
The placebo is a white, round, uncoated tablet.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with treatment-related adverse events - Number of participants with treatment-related adverse events will be collected and the percentage of AE of different grades will be assessed.
Timepoint [1] 0 0
up to 28 days
Secondary outcome [1] 0 0
Maximum plasma drug concentrations (Cmax) - Individual plasma concentrations of ICP-022 will be measured and Cmax will be calculated with noncompartmental analysis using WinNonlin.
Timepoint [1] 0 0
up to 16 days
Secondary outcome [2] 0 0
Time of maximum plasma drug concentrations (Tmax) - Time of maximum plasma drug concentrations (Tmax) of ICP-022 will be recorded.
Timepoint [2] 0 0
up to 16 days
Secondary outcome [3] 0 0
Area under the concentration time curve up to the time "t" (AUC(0-t)) - Area under the concentration time curve up to the time "t" (AUC(0-t)) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.
Timepoint [3] 0 0
up to 16 days
Secondary outcome [4] 0 0
Area under the concentration time curve up to the last data point above LOQ (AUC(last)) - Area under the concentration time curve up to the last data point above LOQ (AUC(last)) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.
Timepoint [4] 0 0
up to 16 days
Secondary outcome [5] 0 0
Apparent half-life for designated elimination phases (t½) - Apparent half-life for designated elimination phases (t½) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.
Timepoint [5] 0 0
up to 16 days
Secondary outcome [6] 0 0
Percent target occupancy - PBMC from individual subject before and after dosing will be collected and the target occupancy will be determined by ELISA. The percent of target occupancy will be compared descritively.
Timepoint [6] 0 0
up to 16 days

Eligibility
Key inclusion criteria
- Healthy male subjects age =18 and =55 years

- Body mass index =19 and =31 kg/m2, with minimum body weight of 50kg

- No clinically significant findings in the medical history and physical examination,
especially with regard to the respiratory, heart, immune system, pancreas, liver, bile
and gastrointestinal systems

- No clinically significant laboratory values and urinalysis, unless the investigator
considers any abnormality to be clinically irrelevant;

- Subjects with a partner of child-bearing potential must be willing to use an approved
form of contraception with a failure rate of <1%. Subjects must be willing to use a
condom during sexual intercourse whether or not their partner is of child-bearing
potential from screening until 90 days after their final study visit.

- Normal electrocardiogram (ECG), blood pressure, and heart rate, unless the
investigator considers any abnormality to be clinically irrelevant

- Informed consent must be obtained in writing for all subjects personally at enrollment
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Subjects with medically important events

- Having 1st degree relative with coronary heart disease at age <60

- Using of prescription drugs including but not limited to those known to interfere with
metabolism of drugs within 30 days prior to dosing

- Exposure to any other medication, including over-the-counter medications, herbal
remedies and vitamins for at least 14 days before randomization (except paracetamol

- Participation in another study with any investigational drug in 30 days or five
half-lives (whichever is longer) preceding the study

- Current smoker, defined as more than 10 cigarettes or equivalent per day before the
beginning of the study (participants currently smoking =10 cigarettes daily and able
to completely stop smoking during the study from screening until follow-up are
eligible)

- Symptoms of a clinically significant illness in the 3 months before the study

- Presence or sequelae of respiratory, gastrointestinal, immune system, heart, liver or
kidney disease, including asymptomatic unconjugated hyperbilirubinemia or asthma, or
other conditions known to interfere with the absorption, distribution, metabolism, or
excretion of drugs

- Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease

- Hemorrhoids or anal diseases with regular or recent presence of blood in feces

- History of immediate hypersensitivity to any medications or any food allergy, and
acute phase of allergic rhinitis in the previous 2 weeks before randomization

- Blood or plasma donation of more than 500 mL during the previous 2 months before
randomization and/or more than 50 mL in the 2 weeks prior to screening, or plan to
donate any additional blood for 12 weeks after completing the study

- Subjects with a positive quantiFERON® test at screening or within 6 months prior to
Day 1

- Positive test for human immunodeficiency virus (HIV)

- Positive test for hepatitis B (surface antigens HBs), or C (antibody HCs), unless
caused by immunization

- Positive urine drug screen within 1 year before randomization

- Positive alcohol screen or active alcoholism

- Mental condition rendering the subject incapable to understand the nature, scope, and
possible consequences of the study

- Subject has difficulty swallowing or is unable to swallow a tablet

- Unlikely to comply with the clinical study protocol eg, uncooperative attitude,
inability to return for follow-up visits, and improbability of completing the study

- Investigator, or any sub-investigator, research assistant, pharmacist, study
coordinator, other staff directly involved in the conduct of the protocol, or first
degree relative thereof

- Subject requires anticoagulation treatment in the past 30 days

- Subject with anemia of any kind

- Subject with pancreatic abnormality of any kind, or elevated Lipase or Amylase >ULN

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
CMAX Clinical Research - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Innocare Pharma Australia Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a single center, randomized, double-blind, placebo-controlled, dose escalation study
in healthy subjects to evaluate the safety, tolerability, pharmacokinetics and
pharmacodynamics of ICP-022 following oral single and multiple escalating dose
administration.
Trial website
https://clinicaltrials.gov/show/NCT03189017
Trial related presentations / publications
Choi J, Kim ST, Craft J. The pathogenesis of systemic lupus erythematosus-an update. Curr Opin Immunol. 2012 Dec;24(6):651-7. doi: 10.1016/j.coi.2012.10.004. Epub 2012 Nov 3. Review.
Holroyd CR, Edwards CJ. The effects of hormone replacement therapy on autoimmune disease: rheumatoid arthritis and systemic lupus erythematosus. Climacteric. 2009 Oct;12(5):378-86. doi: 10.1080/13697130903025449. Review.
Sanz I, Lee FE. B cells as therapeutic targets in SLE. Nat Rev Rheumatol. 2010 Jun;6(6):326-37. doi: 10.1038/nrrheum.2010.68. Review.
Garcia A, De Sanctis JB. A Review of Clinical Trials of Belimumab in the Management of Systemic Lupus Erythematosus. Curr Pharm Des. 2016;22(41):6306-6312. doi: 10.2174/1381612822666160831103254. Review.
Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G; LUNAR Investigator Group. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012 Apr;64(4):1215-26. doi: 10.1002/art.34359. Epub 2012 Jan 9.
Harandi A, Zaidi AS, Stocker AM, Laber DA. Clinical Efficacy and Toxicity of Anti-EGFR Therapy in Common Cancers. J Oncol. 2009;2009:567486. doi: 10.1155/2009/567486. Epub 2009 May 6.
Public notes

Contacts
Principal investigator
Name 0 0
Sepehr Shakib
Address 0 0
CMAX
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications