Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001446358
Ethics application status
Approved
Date submitted
3/10/2017
Date registered
12/10/2017
Date last updated
15/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of the Safety, Tolerability, Immunogenicity, Pharmacokinetics and Pharmacodynamics of Intravenous ATYR1923 in Healthy Volunteers.
Scientific title
A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety,
Tolerability, Immunogenicity, Pharmacokinetics and Pharmacodynamics of Single Doses
of Intravenous ATYR1923 in Healthy Volunteers
Secondary ID [1] 292890 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Interstitial Lung Disease 304736 0
Condition category
Condition code
Respiratory 304054 304054 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is a single infusion, given once, There is no requirement to implement strategies to improve adherence. Any deviations from the protocol mandated infusion requirements will be documented.
Single Ascending Dose (SAD)
Cohort 1 - Single dose of 0.03mg/kg IV administered ATYR1923/placebo over a 60 minute period
Cohort 2 - Single dose of 0.1mg/kg IV administered ATYR1923/placebo over a 60 minute period
Cohort 3 - Single dose of 0.3mg/kg IV administered ATYR1923/placebo over a 60 minute period
Cohort 4 - Single dose of 1.0mg/kg IV administered ATYR1923/placebo over a 60 minute period
Cohort 5 - Single dose of 3.0mg/kg IV administered ATYR1923/placebo over a 60 minute period
Cohort 6 - Single dose of 5.0mg/kg IV administered ATYR1923/placebo over a 60 minute period
Intervention code [1] 299127 0
Treatment: Drugs
Comparator / control treatment
Placebo (Formulation buffer diluted in 0.9% sterile sodium chloride solution)
Control group
Placebo

Outcomes
Primary outcome [1] 303388 0
To assess the safety and tolerability of single ascending IV doses of ATYR1923 in healthy volunteers.
Timepoint [1] 303388 0
Safety and tolerability assessments will consist of AEs, clinical laboratory, vital signs, pulse oximetry, 12-lead ECG, immunogenicity and physical examination. Assessments will be performed at the following timepoints:
AEs – Screening, Day -1, Day 1, Day 2, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29
Urinalysis - Screening, Day -1, Day 1, Day 3, Day 8, Day 15, Day 29
Hematology - Screening, Day -1, Day 2, Day 3, Day 5, Day 8, Day 15, Day 29
Coagulation - Screening, Day -1, Day 3, Day 8, Day 29
Vital signs - Screening, Day -1, Day 1, Day 2, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29
Pulse oximetry - Screening, Day -1, Day 1, Day 8
12-lead ECG - Screening, Day 1, Day 2, Day 5, Day 8, Day 29
Immunogenicity – Screening, Day 1, Day 5, Day 8, Day 15, Day 22, Day 29
Physical examination - Screening, Day -1, Day 3, Day 8, Day 29
Infusion site examination - Day 1
Secondary outcome [1] 338812 0
To characterize the Pharmacokinetics (PK) of single ascending IV doses of ATYR1923 in healthy volunteers.
PK parameters to be assessed include: Cmax, Tmax, AUC0-t, AUC0-168h, AUC0-inf, t1/2, kel, CL, Vss, Vz, MRTlast, MRT0-inf
Timepoint [1] 338812 0
Blood samples for PK analysis of ATYR1923 in serum samples will be taken on the following days and time points:
Day 1 - within 30 minutes pre-dose and 0.5, 1, 2, 4, 8, 12 hours post-start of infusion
Day 2 – 18 and 24 hours post-start of infusion
Day 3 – 48hrs post-start of infusion
Day 5 - 96hrs post-start of infusion
Day 8 - 168hrs post-start of infusion
Day 15 - 336hrs post-start of infusion
Day 22 - 504hrs post-start of infusion
Day 29 - 672hrs post-start of infusion
Secondary outcome [2] 338813 0
To assess the incidence and level of positive ADA in single ascending IV doses of ATYR1923 in healthy volunteers. The analysis of serum ADAs will be performed at a Bioanalytical Laboratory using qualified immunoassay.
Timepoint [2] 338813 0
ADA for Anti-ATYR1923 antibodies – Day 1, Day 5, Day 8, Day 15, Day 22, Day 29
Secondary outcome [3] 339611 0
To assess the incidence and level of positive Jo-1 antibodies in single ascending IV doses of ATYR1923 in blood samples of healthy volunteers. The analysis of serum Jo-1 antibodies will be performed at a Bioanalytical Laboratory using a validated immunoassay.
Timepoint [3] 339611 0
Jo-1 antibody - Screening, Day 1, Day 5, Day 8, Day 15, Day 22, Day

Eligibility
Key inclusion criteria
1. Willing and able to provide written informed consent
2. Healthy male or female subjects, aged greater than or equal to 18 and less than or equal to 55 years inclusive at time of informed consent.
3. Body Mass Index (BMI) greater than or equal to 19.0 to less than or equal to 30.0 kg/m2 and weight greater than or equal to 55 kg and less than or equal to 100kg.
4. Female subjects may be of childbearing potential or of non-childbearing
potential (either surgically sterilized or at least 1 year post-menopausal as
confirmed by amenorrhea duration of at least 12 months and appropriate
levels of serum follicle-stimulating hormone [FSH]). Female subjects of
childbearing potential must be non-pregnant and non-lactating, have a
negative serum pregnancy test at screening and a negative urine pregnancy
test at Day -1 prior to first study drug infusion. Additionally, female subjects
of childbearing potential must be willing to use adequate contraception from screening until 90 days after the last follow-up
visit.
5. Male subjects, if not infertile or surgically sterilized, must agree to use adequate contraception and not donate sperm from Day -1 until 90 days after the last follow-up visit
6. Adequate venous access.
7. Be able to communicate well with the Investigator and site personnel, and
agree to comply with all study procedures and requirements.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Exposure to any prescription medications (small molecules, biologics
including vaccines) or, systemically administered over the counter drugs,
dietary supplements or herbal remedies, within 30 days or 5 half-lives (if
known), whichever is longer, prior to Day -1. An exception is made for
hormonal contraceptives and a limited amount of paracetamol for the
treatment of headache or any other pain.
2. Any condition which (while not requiring regular use of medication) is likely
to require intermittent (as required) therapeutic intervention (e.g., seizure
disorder, seasonal allergies, asthma) at any point during the study.
3. History of significant drug allergies or a history of anaphylactic reaction.
4. History of any clinically significant condition (including and not limited to
the gastrointestinal, renal, hepatic, cardiovascular, respiratory, or neurological
systems) and/ or other major disease or malignancy, as determined by the
Investigator.
5. Major surgery within 3 months prior to Day -1 or anticipated surgery during
the study.
6. Any condition that necessitated hospitalization within the 3 months prior to
Day -1 or is likely to require so during the study.
7. Blood/plasma donation or blood loss greater than or equal to 470 ml within 3 months prior to Day -1.
8. Participation in another clinical study of an investigational agent within
3 months (small molecules) / 6 months (biologics) or 5 half-lives of the agent
(if known), whichever is longer.
9. History of, or positive results of screening for: hepatitis B (hepatitis B surface
antigen [HBsAg]), hepatitis C (anti-hepatitis C virus [HCV] antibodies) or
human immunodeficiency virus (HIV) (antibodies to HIV types 1 and 2).
10. History of drug or alcohol abuse within 12 months prior to Day -1, or
evidence of such abuse on laboratory assays at screening. Drug or alcohol
abuse includes heavy smoking (> 1 pack per day), frequent use of recreational
drug products, and an average intake of more than 24 units of alcohol per
week (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of
wine or 35 mL of spirits).
11. History of alcohol consumption in the 3 days prior to Day -1, or inability to
abstain from alcohol consumption during the study.
12. Clinically significant abnormalities in the screening physical examination,
vital signs, electrocardiogram (ECG) or clinical laboratory tests, as
determined by the Investigator. Repeat testing may be performed at the
Investigator’s discretion.
13. Jo-1 positivity during Screening or past history of Jo-1 positivity.
14. Unable to refrain from strenuous activity for a period of 4 days before Day -1
and for the duration of the study.
15. Unlikely to comply with the clinical study protocol; e.g., uncooperative
attitude, inability to return for follow-up visits, and improbability of
completing the study.
16. Any other condition, which in the opinion of the Investigator precludes the
subject’s participation in the clinical study.
17. Significant and/or acute illness within 5 days prior to (the first) drug
administration that may impact safety assessments, in the opinion of the
Investigator.
18. An employee of the Contract Research Organization (CRO) or the Sponsor.

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)
Allocation involves contacting the holder of the allocation schedule (unblinded pharmacist) who is at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised 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
Intervention assignment
Other
Other design features
Participants will be assigned to different dosages or placebo depending on which cohort they are enrolled into. This study will be performed in adult healthy volunteers (up to 36 subjects in 6 cohorts). The study will commence with Cohort 1 and progression to subsequent cohorts will be subject to review of safety and tolerability data generated from the previous cohorts. In general, each cohort consists of an eligibility/screening period of up to 3 weeks, a treatment period involving administration of a single dose of ATYR1923 (study drug) or placebo and a 4-week follow-up period.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2017
Actual
16/11/2017
Date of last participant enrolment
Anticipated
19/03/2018
Actual
23/03/2018
Date of last data collection
Anticipated
19/04/2018
Actual
20/04/2018
Sample size
Target
36
Accrual to date
Final
36
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9032 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 17513 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 297520 0
Commercial sector/Industry
Name [1] 297520 0
aTyr Pharma, Inc.
Country [1] 297520 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
INCResearch Australia Pty Ltd
Address
159 Port Road
Hindmarsh SA 5007
Country
Australia
Secondary sponsor category [1] 296530 0
None
Name [1] 296530 0
Address [1] 296530 0
Country [1] 296530 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298617 0
Alfred Human Research Ethics Committee
Ethics committee address [1] 298617 0
Ethics committee country [1] 298617 0
Australia
Date submitted for ethics approval [1] 298617 0
04/10/2017
Approval date [1] 298617 0
03/11/2017
Ethics approval number [1] 298617 0

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

Contacts
Principal investigator
Name 77666 0
Dr Jason Lickliter
Address 77666 0
Nucleus Network
Level 5, Burnet Tower, AMREP Precinct
Commercial Road,
Melbourne VIC 3004
Country 77666 0
Australia
Phone 77666 0
+61 390768609
Fax 77666 0
Email 77666 0
[email protected]
Contact person for public queries
Name 77667 0
Sally Johnsson
Address 77667 0
INCResearch Australia Pty, Ltd
159 Port Road Hindmarsh SA 5007 (head office)
Suite 1, Level 2, 924 Pacific Highway, Gordon NSW 2072 (actual office location of personnel)
Country 77667 0
Australia
Phone 77667 0
+61 284379283
Fax 77667 0
Email 77667 0
[email protected]
Contact person for scientific queries
Name 77668 0
David Fuller
Address 77668 0
INCResearch Australia Pty, Ltd
Suite 1, Level 2, 924 Pacific Highway
Gordon NSW 2072
Country 77668 0
Australia
Phone 77668 0
+61 284379238
Fax 77668 0
Email 77668 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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