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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03622021




Registration number
NCT03622021
Ethics application status
Date submitted
27/07/2018
Date registered
9/08/2018
Date last updated
21/09/2020

Titles & IDs
Public title
A Study of AK111 in Healthy Subjects
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Dose-Escalation First-In-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AK111 in Healthy Subjects
Secondary ID [1] 0 0
AK111-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Psoriasis 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AK111 or Placebo

Experimental: AK111 30mg - Single dose of 30mg AK111 or placebo is administered subcutaneously to healthy subjects

Experimental: AK111 75mg - Single dose of 75mg AK111 or placebo is administered subcutaneously to healthy subjects

Experimental: AK111 150mg - Single dose of 150mg AK111 or placebo is administered subcutaneously to healthy subjects

Experimental: AK111 300mg - Single dose of 300mg AK111 or placebo is administered subcutaneously to healthy subjects

Experimental: AK111 450mg - Single dose of 450mg AK111 or placebo is administered subcutaneously to healthy subjects

Experimental: AK111 600mg - Single dose of 600mg AK111 or placebo is administered subcutaneously to healthy subjects


Treatment: Drugs: AK111 or Placebo
All the subjects in each cohort will be randomized in a 3:1 ratio to receive either AK111 or Placebo.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of treatment emergent AE/SAEs
Timepoint [1] 0 0
From baseline through 12 weeks
Secondary outcome [1] 0 0
The endpoint for assessment of PD including the change from baseline in serum IL-17A level and serum cytokines.
Timepoint [1] 0 0
From baseline through 12 weeks
Secondary outcome [2] 0 0
Area under the concentration curve (AUC) of AK111
Timepoint [2] 0 0
From baseline through 12 weeks
Secondary outcome [3] 0 0
Maximum observed concentration (Cmax) of AK111
Timepoint [3] 0 0
From baseline through 12 weeks
Secondary outcome [4] 0 0
Number of subjects who develop detectable anti-drug antibodies (ADAs) [
Timepoint [4] 0 0
From baseline through 12 weeks

Eligibility
Key inclusion criteria
Subjects must meet all of the following inclusion criteria (as applicable) to be eligible
for participation in this study.

1. Have the ability to understand and sign a written informed consent form (ICF), which
must be obtained prior to initiation of study procedures.

2. Female or male between 18 and 55 years of age, inclusive, at screening.

3. Must have a calculated body mass index (BMI) 19 = BMI = 32(inclusive) at screening,
and a total body weight = 50 kg for male or = 45 kg for female at screening.

4. Females of child bearing potential must have a negative pregnancy test in serum at
screening and a negative serum pregnancy test on Day -1, either be of non-child
bearing potential, defined as being:

1. Postmenopausal (for at least 2 years before screening), verified by serum
follicle stimulating hormone (FSH) level >40 mIU/mL at screening, or

2. Permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral
salpingectomy), or

3. Congenitally sterile

5. Women of child-bearing potential must use one of the following methods of
contraception, from screening until at least 120 days after dosing:

A highly effective method with a failure rate of less than 1%:

- Implant contraceptive (e.g. Jadelle)

- Intra-uterine device (IUD) containing either copper or levonorgestrel (e.g.
Mirena)

- Male sterilization (vasectomy)

- Female sterilization (e.g. by bilateral tubal ligation ('tying tubes') or
hysterectomy)

A method for which the failure rate is between 5% and 10% in real life use, in
combination with a barrier method (male condom):

- Injectable contraceptive (e.g. Depo Provera)

- Oral Contraceptive Pill (combined hormonal pill or progestogen-only 'mini-pill')

- Vaginal contraceptive ring (e.g. NuvaRing) Please note that condoms alone are not
highly effective methods of contraception. Periodic abstinence, the rhythm
method, and the withdrawal method are not acceptable methods of birth control.

6. Nonsterilized male subjects who are sexually active with a female partner of
childbearing potential must use an effective method of contraception as listed above
from Day 1 through 120 days after receipt of the last dose of study medication. It is
strongly recommended for the female partner of a male subject to also us an effective
method of contraception throughout this period.

7. Must, in the opinion of the Investigator, be in good general health based upon medical
history, physical examination (including vital signs), 12-lead ECG and clinical
laboratory tests must fall within the clinical laboratory's reference normal ranges
unless the results have been determined by the Investigator to have no clinical
significance).

8. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other study procedures as specified in the protocol.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria Subjects who meet any of the following exclusion criteria will not be
enrolled in this study.

1. Subjects who are investigational site staff members or subjects who are Sponsor
employees directly involved in the conduct of the study.

2. Are pregnant, nursing, or planning pregnancy within 120 days following the last dose
of study medication (both men and women) while enrolled in the study.

3. Have previously participated in an investigational trial involving administration of
any investigational compound within 3 months or 5 half-lives (whichever is longer)
prior to the study dosing, or currently participating in another clinical study.

4. Have a planned surgical intervention for a pretreatment condition within the duration
of the trial, including the follow up period.

5. Have used any biologic within the previous 12 months prior to the study dosing.

6. Use of any of the following, unless agreed as non-clinically relevant by the
Investigator: Prescription medication within 4 weeks prior to the study dosing;
Over-the-counter medication (excluding paracetamol) within 7 days prior to the study
dosing. Paracetamol use must be limited to 2 g per day and no more than 3 days usage
in the 4 weeks prior to the study dosing; Vitamin therapy or dietary supplements
within 7 days prior to the study dosing and for the duration of the study; Herbal
supplements within 4 weeks prior to the study dosing and for the duration of the
study. Medications which are known CYP P450 isoenzyme substrates/inducers/inhibitors
must be excluded within 4 weeks prior to study dosing and for the duration of the
study.

7. Current acute infection or history of acute infection within 7 days prior to receipt
of the study drug; additionally, aural temperature that exceeds 37.4°C at Day -1
(baseline).

8. Have had a serious infection, define as requiring intravenous antibiotics or
hospitalization within 3 months prior to screening; Have had recurrent or chronic
infection, define as = 3 infections requiring anti-microbials over the past 12 months
prior to screening.

9. Have a history of latent or active granulomatous infection, including histoplasmosis,
candidiasis (clinically significant candidiasis or recurrent candidiasis), or
coccidioidomycosis prior to screening, or a history of any other infectious disease
within 4 weeks prior to screening that in the opinion of the investigator, affects the
subject's ability to participate in the trial.

10. History or complication of tuberculosis, or evidence of latent tuberculosis by
QuantiFERON screening. If the QuantiFERON®-TB Gold test is indeterminate, a retest is
allowed if results can be obtained. If the retest is also indeterminate, the subject
will be excluded from the study. Subjects who have had household contact with a person
with active TB are excluded.

11. Positive for hepatitis B surface antigen, hepatitis C antibodies or HIV at screening.

12. Have had a substance abuse (drug or alcohol) problem within the previous 3 years, or a
positive urine drug screen at screening.

13. History of regular alcohol consumption exceeding 14 drinks/week for females or 21
drinks/week for males (1 drink = 100 mL of wine or 360 mL of beer or 45 mL of hard
liquor) within 6 months of screening.

14. Use of tobacco or nicotine containing products (including e-cigarettes) at any time
within six months before screening and for the duration of the study.

15. Have poor venous access and are unable to donate blood.

16. Have donated blood within 90 days prior to the study dosing.

17. Have a history of multiple drug allergies or a known allergy or hypersensitivity to
any biologic therapy at screening that is important in the opinion of the
Investigator.

18. Have a known allergy or reaction to any component of the AK111 formulation.

19. Have a history of known demyelinating diseases such as multiple sclerosis or optic
neuritis.

20. Have a history of lymphoproliferative disease, including lymphoma, or signs suggestive
of possible lymphoproliferative disease such as lymphadenopathy of unusual size or
location, or clinically significant splenomegaly.

21. Have any known malignancy or have a history of malignancy within the previous 5 years
(with the exception of a non-melanoma skin cancer that has been treated with no
evidence of recurrence).

22. Have a transplanted organ (with the exception of a corneal transplant performed > 3
months prior to the study dosing).

23. Have an implanted defibrillator or pacemaker.

24. 12-lead ECG demonstrating QTc interval > 450 msec corrected using the Fridericia's
formula (QTcF) at screening from average of three ECGs obtained (separated by
approximately 1-minute intervals) after 5 minutes of supine rest.

25. Blood pressure >140 mmHg (systolic) or > 90 mmHg (diastolic) at screening, following
at least 5 minutes of supine rest. If blood pressure (BP) is >140 mmHg (systolic) or
>90 mmHg (diastolic), the BP should be repeated two more times and the average of the
three BP values should be used to determine the subject's eligibility.

26. Have had a live vaccination within 12 weeks prior to the study dosing, or intend to
have a live vaccination during the course of the study, or have participated in a
vaccine clinical trial within 12 weeks prior to the study dosing.

27. Have any psychiatric or serious or active medical illness which, in the opinion of the
Investigator, would interfere with subject treatment, assessment, or compliance with
the protocol. This would include renal, cardiac, hematological, hepatic, pulmonary
(including chronic asthma), endocrine (eg, diabetes), central nervous,
gastrointestinal (including but not limit to Crohn's disease, ulcerative colitis, an
ulcer), vascular, metabolic (thyroid disorders, adrenal disease), or immunodeficiency
disorders that are clinically significant or requiring treatment.

28. Are believed, by the Investigator, to be inappropriate for study participation for any
reason.

Study design
Purpose of the study
Other
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 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
14/08/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/02/2020
Sample size
Target
Accrual to date
Final
68
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Christchurch

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1, randomized, double-blind, placebo-controlled, single dose-escalation
first-in human study to evaluate the safety, tolerability, PK, PD and immunogenicity of AK111
in healthy subjects following SC administration. The study will consist of cohorts of healthy
subjects. Cohort 1, four unique subjects will be randomized to receive either active AK111
(N=3) or matching placebo (N=1). Cohorts 2, 3, 4 and 5, eight unique subjects will be
randomized to receive either active AK111 (N=6) or matching placebo (N=2). Approximately 36
subjects will be treated in this study.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03622021
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03622021