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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03285620




Registration number
NCT03285620
Ethics application status
Date submitted
15/08/2017
Date registered
18/09/2017
Date last updated
12/06/2019

Titles & IDs
Public title
A Study of AL-034 to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses in Healthy Participants
Scientific title
A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-human Study of Orally Administered AL-034 to Evaluate the Safety, Tolerability, and Pharmacokinetics After Single Ascending Doses Including Food Effect Evaluation (Part 1) and After Multiple Ascending Doses (Part 2) in Healthy Adult Subjects
Secondary ID [1] 0 0
AL-034-1201
Secondary ID [2] 0 0
AL-034-1201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AL-034
Treatment: Drugs - Placebo

Experimental: Part 1: Single Ascending Dose (SAD) - Participants will receive single oral dose of AL-034 (oral solution) (the starting dose in Cohort 1 of Part 1 will be 0.2 milligram \[mg\]) or matching placebo under fasted condition (Cohorts 1 to 5 or optional Cohort 7) on Day 1. Participants may receive AL-034 in a fed state (Cohort 6) to evaluate the effect of food on the pharmacokinetics (PK) of AL-034.

Experimental: Part 2: Multiple-Dose Administration (MAD) - Participants will receive multiple oral doses of AL-034 or matching placebo for 4 consecutive weeks either once weekly (Qwk - for 4 doses) or every two weeks (Q2wk - for 3 doses) under fed or fasted conditions. The starting dose for Part 2 will be determined based on the initial PK and safety/tolerability data from Part 1.


Treatment: Drugs: AL-034
Participants will receive single oral dose of AL-034 under fed or fasted conditions in part 1 and part 2

Treatment: Drugs: Placebo
Participants will receive single oral dose of matching placebo (oral solution) under fed or fasted conditions in part 1 and part 2.

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

Outcomes
Primary outcome [1] 0 0
Part 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
Timepoint [1] 0 0
Approximately up to 9 weeks
Primary outcome [2] 0 0
Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
Timepoint [2] 0 0
Approximately up to 12 weeks
Primary outcome [3] 0 0
Part 1: Number of Participants With AEs by Severity
Timepoint [3] 0 0
Approximately up to 9 weeks
Primary outcome [4] 0 0
Part 2: Number of Participants With AEs by Severity
Timepoint [4] 0 0
Approximately up to 12 weeks
Primary outcome [5] 0 0
Part 1: Number of Participants with Clinically Significant Changes in Physical Examination
Timepoint [5] 0 0
Approximately up to 9 weeks
Primary outcome [6] 0 0
Part 2: Number of Participants with Clinically Significant Changes in Physical Examination
Timepoint [6] 0 0
Approximately up to 12 weeks
Primary outcome [7] 0 0
Part 1: Number of Participants with Vital Sign Abnormalities
Timepoint [7] 0 0
Approximately up to 9 weeks
Primary outcome [8] 0 0
Part 2: Number of Participants with Vital Sign Abnormalities
Timepoint [8] 0 0
Approximately up to 12 weeks
Primary outcome [9] 0 0
Part 1: Number of Participants with Laboratory Abnormalities
Timepoint [9] 0 0
Approximately up to 9 weeks
Primary outcome [10] 0 0
Part 2: Number of Participants with Laboratory Abnormalities
Timepoint [10] 0 0
Approximately up to 12 weeks
Primary outcome [11] 0 0
Part 1: Number of Participants with Holter Monitoring Abnormalities
Timepoint [11] 0 0
Approximately up to 9 weeks
Primary outcome [12] 0 0
Part 2: Number of Participants with Holter Monitoring Abnormalities
Timepoint [12] 0 0
Approximately up to 12 weeks
Primary outcome [13] 0 0
Part 1: Number of Participants with Electrocardiogram (ECG) Abnormalities
Timepoint [13] 0 0
Approximately up to 9 weeks
Primary outcome [14] 0 0
Part 2: Number of Participants with Electrocardiogram (ECG) Abnormalities
Timepoint [14] 0 0
Approximately up to 12 weeks
Primary outcome [15] 0 0
Part 1: Number of Participants with Cytokine Release Syndrome (CRS)
Timepoint [15] 0 0
Approximately up to 9 weeks
Primary outcome [16] 0 0
Part 2: Number of Participants with Cytokine Release Syndrome (CRS)
Timepoint [16] 0 0
Approximately up to 12 weeks
Primary outcome [17] 0 0
Part 1: Number of Participants with Cytokine Release Syndrome (CRS) by Severity
Timepoint [17] 0 0
Approximately up to 9 weeks
Primary outcome [18] 0 0
Part 2: Number of Participants with Cytokine Release Syndrome (CRS) by Severity
Timepoint [18] 0 0
Approximately up to 12 weeks
Primary outcome [19] 0 0
Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-034 Following Single Dose Administration in Fasted State
Timepoint [19] 0 0
Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
Primary outcome [20] 0 0
Part 2: Maximum Observed Plasma Concentration (Cmax) of AL-034 Following Repeated Dose Administration
Timepoint [20] 0 0
Days 1, 22, and 29: predose, and 0.5, 1, 2, and 12 hours postdose
Primary outcome [21] 0 0
Part 1: Area Under the Plasma Concentration Time Curve (AUC) of AL-034 Following Single Dose Administration in Fasted State
Timepoint [21] 0 0
Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
Primary outcome [22] 0 0
Part 2: Area Under the Plasma Concentration Time Curve (AUC) of AL-034 Following Repeated Dose Administration
Timepoint [22] 0 0
Days 1, 22, and 29: predose, and 0.5, 1, 2, and 12 hours postdose
Primary outcome [23] 0 0
Part 1: AL-034 Concentration in Urine Following a Single Dose Administration
Timepoint [23] 0 0
Day 1: 0 to 6, 6 to 12, and 12 to 24 hours postdose
Primary outcome [24] 0 0
Part 2: AL-034 Concentration in Urine Following Repeated Dose Administration
Timepoint [24] 0 0
Day 1: 0 to 6, 6 to 12, and 12 to 24 hours postdose
Secondary outcome [1] 0 0
Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-034 Following Single Dose Administration in Fed State
Timepoint [1] 0 0
Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose
Secondary outcome [2] 0 0
Part 2: Area Under the Plasma Concentration Time Curve (AUC) of AL-034 Following Single Dose Administration in Fed State
Timepoint [2] 0 0
Day 1: predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose

Eligibility
Key inclusion criteria
INCLUSION CRITERIA Each potential participant must satisfy all of the following criteria to be enrolled in the study

* participant must be a man or a woman between 18 and 55 years of age, extremes included
* Female participant must be of non-childbearing potential, defined as: a) Postmenopausal: A postmenopausal state is defined as no menses for 12 months without an alternative medical explanation. A high follicle stimulating hormone (FSH) level (greater than [>]40 international unit per liter [IU/L] or milli international unit per milliliter [mIU/mL]) in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, 2 FSH measurements will have to be taken at least 3 months apart, OR b) Permanently sterile - permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy Male participants must either: a) be surgically sterile (have had a vasectomy), or otherwise incapable of fathering a child, OR b) if heterosexually active, have a partner who is postmenopausal (as defined above), permanently sterile (as defined above), or otherwise incapable of becoming pregnant, OR c) if heterosexually active with a woman of childbearing potential, agree to use effective methods of contraception as detailed in Prohibitions and Restrictions section, from screening onwards, and agree to continue to use the same method of contraception throughout the study and for at least 90 days after the last dose of study drug Contraceptive use should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
* Female participants should have a negative pregnancy test at screening and on Day -1
* Participants must be non-smokers for at least 3 months prior to screening
* Participants must have a body mass index (BMI; weight in kilogram [kg] divided by the square of height in meters) of 18.0 to 30.0 kilogram per meter square (kg/m^2), extremes included. (Williamson 1993)
* Participants must have a normal 12-lead electrocardiogram (ECG) (based on the mean value of the triplicate parameters) at screening including: a) Normal sinus rhythm (heart rate between 50 and 100 beats per minute [bpm], extremes included); b) QT interval corrected for heart rate (QTc) according to Fridericia's formula (QTcF) less than or equal to (<=)450 millisecond (ms) (Fridericia 1920); c) QRS interval less than (<)120 ms; d) PR interval <=200 ms; e) ECG morphology consistent with healthy cardiac conduction and function. Any evidence of heart block is exclusionary. Any evidence of left or right bundle branch block is exclusionary Note: Retesting for abnormal QTc interval value that may lead to exclusion will be allowed once without prior approval from the Sponsor. Retesting may take place during an unscheduled visit in the screening phase. Participants with a normal value at retest may be included
* Participants must be healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, medical history, vital signs, and the results of blood chemistry, blood coagulation and hematology tests, and a urinalysis performed at screening
* Participant must be willing and able to adhere to the prohibitions and restrictions specified in Prohibitions and Restrictions section
* In the Investigator's opinion, the participant is able to understand and comply with protocol requirements, instructions, and study restrictions and is likely to complete the study as planned
* Participant must sign a separate if he or she agrees to provide an optional deoxyribonucleic acid (DNA) sample for research. Refusal to give consent for the optional DNA research sample does not exclude a participant from participation in the study

EXCLUSION CRITERIA Any potential participant who meets any of the following criteria will be excluded from participating in the study

* Participants with a past history of cardiac arrhythmias (for example, extrasystoli, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (for example, hypokalemia, family history of long QT Syndrome) or history or other clinical evidence of significant or unstable cardiac disease (for example, angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease, and/or clinically significant ECG abnormalities), moderate to severe valvular disease or uncontrolled hypertension at screening. Any evidence of heart block or bundle branch block is also exclusionary
* Participants with any current or previous illness that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant or that could prevent, limit, or confound the protocol specified assessments. This may include but is not limited to renal dysfunction (estimated creatinine clearance below 60 milliliter per minute [mL/min] at screening, calculated by the Modification of Diet in Renal Disease [MDRD] formula [Poggio 2005]), significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, or constipation that in the Investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, ophthalmic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances. Any condition possibly affecting drug absorption (for example, gastrectomy or other significant gastrointestinal tract surgery, such as gastroenterostomy, small bowel resection, or active enterostomy) will also lead to exclusion
* Participants with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, and urticaria
* Participants with a history of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy witnessed in previous studies with experimental drugs
* Participants with a history or current evidence of use of alcohol, amphetamines, barbiturates, recreational or narcotic drug use within the past 1 year, which in the Investigator's opinion would compromise Participant's safety and/or compliance with the study procedures
* Participants with current hepatitis A virus (HAV) infection (confirmed by HAV antibody immunoglobulin M [IgM]), hepatitis A virus (HBV) infection (confirmed by hepatitis A virus [HBsAg]), and hepatitis C virus (HCV) infection (confirmed by HCV antibody) at screening. Evidence of clinically relevant active infection that would interfere with study conduct or its interpretation is also exclusionary
* Participants with current human immunodeficiency virus (HIV) type 1 (HIV-1) or type 2 (HIV-2) infection (confirmed by antibodies) at screening
* Male participants with pregnant partners
* Male participants who plan to father a child while enrolled in this study or within 90 days after the last dose of study drug
* Participants who have taken any disallowed therapies as noted in Prohibitions and Restrictions Section, and Concomitant Medications Section, before the planned first dose of study drug
* Participants having used immune-modulating agents within 6 months prior the first dosing of study drugs, for example, immunosuppressants, interferon alpha (IFN-alpha), or oral corticosteroids
* Participants having received an investigational agent or investigational vaccine or used an invasive investigational medical device within 12 weeks, or having received a biological product within 12 weeks or 5 half-lives (whichever is longer) prior to the first dosing of study drugs
* Participants participating in another clinical or medical interventional research study
* Participants with a) Greater than or equal to (>=) Grade 1 laboratory abnormalities at screening as defined by the Division of Acquired Immune Deficiency Syndrome (DAIDS) Toxicity Grading Scale; or b) Total bilirubin outside the normal range Note: Retesting of abnormal laboratory values that may lead to exclusion will be allowed once without prior asking approval from the Sponsor. Retesting will take place during an unscheduled visit in the screening phase. Participants with a normal value at retest may be included
* Participants who had major surgery (for example, requiring general anesthesia) within 12 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study, or within 12 weeks after the last dose of study drug Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate
* Participant is an employee of the Sponsor, the Investigator or study site, with direct involvement in the proposed study or other studies under the direction of that Investigator or study site, as well as family members of the employees or the investigator NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. If a participant's clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study drug is given or before the follow-up period, such that he or she no longer meets all eligibility criteria, then the participant should be excluded from participation in the study
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria

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 assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
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)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alios Biopharma Inc.
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Alios Biopharma Inc. Clinical Trial
Address 0 0
Alios Biopharma Inc.
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.