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Trial registered on ANZCTR


Registration number
ACTRN12618001210268
Ethics application status
Approved
Date submitted
23/06/2018
Date registered
19/07/2018
Date last updated
29/01/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Randomized, Placebo-Controlled, Sequential Single and Multiple Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral BT-11 in Healthy Adult Male and Female Volunteers
Scientific title
A Randomized, Placebo-Controlled, Sequential Single and Multiple Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral BT-11 in Healthy Adult Male and Female Volunteers
Secondary ID [1] 295211 0
BT-11-1a
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Inflammatory Bowel Disease 308357 0
Ulcerative colitis 308358 0
Crohn's Disease 308359 0
Condition category
Condition code
Inflammatory and Immune System 307353 307353 0 0
Autoimmune diseases
Oral and Gastrointestinal 307654 307654 0 0
Crohn's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
For single ascending dose, five dose target ranges of BT-11 (depending on body weight the doses in each cohort will be 5.9 – 7.7 mg/kg; 18.9 – 25.0 mg/kg; 44.3 – 50.0 mg/kg; 68.5 – 75 mg/kg and 94.2 – 100.0 mg/kg) will be evaluated, based on subject’s weight on Day 1.

For multiple ascending dose (once daily for 7 days), three dose target ranges of BT-11 (depending on body weight the doses in each cohort will be 5.9 – 7.7 mg/kg; 44.3 – 50.0 mg/kg; and 94.2 – 100.0 mg/kg) will be evaluated, based on subject’s weight on Day 1.

White tablets containing 500 mg BT-11 or matching placebo tablets will be dispensed.

Single ascending dose duration of administration will be once. For multiple ascending dose it will be up to 7 days.
The mode administration will be oral tablet.
Compliance and adherence to the intervention will be performed based on the tablet return, tablet not consumed by the subject.

The safety monitoring committee will evaluate safety at conclusion of single ascending cohort 2 prior to the commencement of dosing for the multiple ascending dose.
Intervention code [1] 301550 0
Treatment: Drugs
Comparator / control treatment
BT-11 Placebo (Finished Product), 500 mg Oral Tablets

Composition of the placebo treatment are as follows:
Pregelatinized starch
108
mg

Sodium Starch Glycolate
35
mg

Talc
35
mg

Crospovidone
30
mg

Magnesium Stearate
20
mg

Polyvinylpyrrolidone K30
15
mg

Silicon dioxide
15
mg
Control group
Placebo

Outcomes
Primary outcome [1] 306318 0
To assess the safety and tolerability of BT-11 after single and multiple ascending oral dose administration in healthy volunteers

The safety and tolerability profile of BT-11 as evidenced by the occurrence, timing, frequency, and severity of adverse events (AE) and clinically significant:

o laboratory abnormalities
Haematology, Coagulation, Serum Chemistry, Urinalysis, HIV, HBsAg, HCV
o physical exam findings
Complete physical exam include, at a minimum, assessment of the following systems: skin, head, ears, eyes, nose and throat, respiratory system, cardiovascular system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the musculoskeletal system
o 12-lead ECG aberrations
ECG data (RR, PR, QRS, QT and QTcF intervals and pulse rate)
o and/or vital signs abnormalities
Vital signs assessments will include systolic and diastolic blood pressure, pulse, tympanic body temperature, and respirations
There were no observe adverse event level up to > 1000 mg/kg of BT-11.
Timepoint [1] 306318 0
Adverse events will be recorded from the time of first dosing through to end of study date.

Laboratory abnormalities at the screening visit, up to 28 days prior to the first dose of study medication then up to end of study visit.

Physical Exam findings will be collected at screening, Day-1 and Day 2 for the single ascending dose. For multiple ascending dose it will be collected at screening, Day-1, Day 3, Day 5 and Day 7

12-lead ECG aberrations will be collected from Screening then on Day -1 and Day 2 for the single ascending dose. For MAD it will be collected at screening, Day-1, Day 3, Day 5 and Day 7

Vital signs abnormalities collected from Screening then on Day -1 and Day 2 for the single ascending dose. For MAD it will be collected at screening, Day-1, Day 3, Day 5 and Day 7
Primary outcome [2] 306705 0
To assess the safety and tolerability of BT-11 after single and multiple ascending oral dose administration in healthy volunteers.
Timepoint [2] 306705 0
For single ascending dose blood samples for PK analysis will be collected pre-dose and at 15, 30, 45 minutes, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose

Urine samples for PK analysis will be collected pre-dose and 0-24 hours post-dose;

For multiple ascending blood samples for PK analysis will be collected pre-dose and at 15, 30, and 45 min and 1, 1.25 1.5, 2, 3, 4, 6, 8, 10, 12 and 18 hours post Day 1 dose. Pre-dose on Day 2

Urine samples for PK analysis will be collected on Day 1, pre-dose and at 0-24 hours post-dose

On follow up period, Day 3 to Day 6, Plasma samples for PK analysis will be collected pre-dose on each day.
Secondary outcome [1] 348163 0
The following PK parameters will be determined:
• Time to maximum concentration (tmax);
• Maximum concentration (Cmax);
• Area under the concentration-time curve from time 0 to last measurable time-point (AUC0–tlast);
• Area under the concentration-time curve from time 0 to infinity (AUC0–inf);
• Terminal Elimination Rate Constant (kel);
• Terminal half-life (t1/2);
• Terminal clearance (CL/F);
• Volume of distribution (Vd/F).
Timepoint [1] 348163 0
The following PK parameters will be determined for single ascending dose:

Area under the concentration-time curve from time 0 to 24 hours from start of first dose (AUC0-24h);
• Amount of drug excreted in urine in each collection interval

For the multiple ascending dose:
Area under the concentration-time curve from time 0 to 24 hours from start dosing (AUC0-24h) on Day 1 and 0 to 24 hours (AUC0-24h) following the last dose on Day 7;
• Pre-dose trough on Days 2, 3, 4, 5 and 6;
• Amount of drug excreted in urine in each collection interval;
• Volume of distribution at steady state (Vss/F).
Secondary outcome [2] 349306 0
To explore the effects of BT-11 on the following parameters after single and multiple ascending oral dose administration in healthy volunteers including but not limited to the following cytokines: TNF-a, IFN-?, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70 and IL- 13
Timepoint [2] 349306 0
Blood samples for pharmacodynamic analysis will be collected pre-dose and at 2, 4, 8, 12 and 24 hours post-dose

For blood samples for pharmacodynamic analysis will be collected pre-dose and at 4 hours post-dose on Day 1 and 2 then at 4 hours post-dose on Day 5

Eligibility
Key inclusion criteria
1. Healthy male and female volunteers aged 18 to 65 years, inclusive.
2. Body weight 65 - 85 kg.
3. Body Mass Index (weight in kg divided by square of height in meters) 19-31 kg/m2, inclusive.
4. Male volunteers must agree to abstain, between dosing and 30 days post-dosing, from sexual intercourse with pregnant or lactating women and, if sexually active with a female partner, to use a condom in addition to his female partner’s use of another form of contraception (e.g., IUD, diaphragm, oral contraceptive, injectable progesterone contraceptive, subdermal implant contraceptive, or tubal ligation). A male practicing abstinence is also acceptable.
5. Female subjects of child-bearing potential, with a fertile male sexual partner, should be willing to use adequate contraception from Day 1 until 30 days after the follow-up visit. Adequate contraception is defined as an intrauterine device combined with at least one of the following forms of contraception: a diaphragm or cervical cap, or a condom. Also, total abstinence, in accordance with the lifestyle of the subject, is acceptable.
6. Volunteer agrees not to take any concomitant medications, including prescriptions or over-the-counter (OTC) medications during the interval from 3 days prior to dosing until after the last PK blood draw for the study.
7. Volunteer agrees not to consume alcohol during the interval from 3 days prior to dosing until after the last PK blood draw for the study.
8. Volunteer is able to communicate effectively with study personnel.
9. Volunteer is able to understand and comply with protocol and investigative site requirements, instructions, and restrictions.
10. Volunteer has read, confirmed understanding of, and signed the written informed consent form after the nature of the study and all essential elements of the informed consent document have been fully explained and all of the Volunteer’s questions have been answered to his or her satisfaction, prior to initiation of any study procedures.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any clinically significant abnormality identified in the screening history, physical examination (including Vital Signs), laboratory testing, or electrocardiographic testing. Repeat testing of vital signs to confirm the value is allowed. Up to two repeat tests are permitted to confirm eligibility.
2. An excessive fall in blood pressure on orthostatic testing at screening or Day –1 (i.e., a fall in systolic blood pressure > 25 mmHg or in diastolic blood pressure > 15 mmHg).
3. Any 12-lead ECG finding at screening or on Day –1 that may, in the opinion of the Investigator, compromise interpretation of ECGs for cardiac safety assessment or complicate interpretation of events that may occur post-dose (e.g., QT not accurately measurable, conduction abnormalities)
4. Positive test for HIV, hepatitis B surface antigen, or hepatitis C antibody.
5. Any clinically significant cardiac, pulmonary, renal, metabolic, neurologic, or other medical, behavioural, or genetic condition.
6. Any condition that places the volunteer at significantly increased risk or may risk compromise of study objectives.
7. Use of prescription or non-prescription drugs 3 days or 5 half-lives (whichever is longer) prior to dosing to after last PK draw.
8. Use of herbal supplements within 3 days or 5 half-lives (whichever is longer) prior to the first dose of study drug to after last PK draw.
9. Use of alcohol within 72 hours prior to first dose of study drug.
10. History of drug or alcohol abuse (by DSM-IV definition) within 3 months prior to screening.
11. Positive urine drug screen (including cotinine, cannabis, cocaine, opiates, amphetamines, and other tests as determined by Investigator). Repeating analyses will be allowed if the PI suspects that there might be false positive results.
12. Volunteer has a contraindication to blood sampling or is considered to have insufficient peripheral venous access.
13. Volunteer has donated blood or blood products in volumes of 450 mL or more within 30 days prior to study enrollment.
14. Volunteer has been previously exposed to BT-11.
15. Volunteer has participated in a study of any investigational drug, device, biologic, or other agent within 30 days prior to study enrollment.
16. Volunteer has known hypersensitivity to BT-11 or any of its constituents.
17. Volunteer has any disorder (e.g., psychiatric, addictive) that, in Investigator’s judgement, may compromise his/her ability to provide legal written informed consent.

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)
Sealed opaque envelopes
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
Parallel
Other design features
Sequential
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
12/07/2018
Date of last participant enrolment
Anticipated
21/09/2018
Actual
Date of last data collection
Anticipated
19/10/2018
Actual
Sample size
Target
70
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 11149 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 22974 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 299799 0
Commercial sector/Industry
Name [1] 299799 0
Landos Biopharma Australia Pty. Ltd.
Country [1] 299799 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Landos Biopharma Australia Pty Ltd
Address
Landos Biopharma Australia Pty Ltd.
Suite 3, 2190 Gold Coast Highway,
Miami, Queensland 4220, Australia
Country
Australia
Secondary sponsor category [1] 299148 0
None
Name [1] 299148 0
Address [1] 299148 0
Country [1] 299148 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300682 0
Bellberry Human Research Ethics Committe H TGA HREC Code: EC00459
Ethics committee address [1] 300682 0
129 Glen Osmond Road
Eastwood South Australia 5063
Ethics committee country [1] 300682 0
Australia
Date submitted for ethics approval [1] 300682 0
23/05/2018
Approval date [1] 300682 0
06/07/2018
Ethics approval number [1] 300682 0

Summary
Brief summary
This is a double-blind, placebo controlled, ascending dose, multi-cohort trial. The study will be conducted with a single ascending dose (SAD) phase and a multiple ascending dose (MAD) phase. In SAD, participants will receive one dose of BT-11 or placebo. In MAD, participants will receive multiple doses of BT-11 or placebo for 7 consecutive days. In both parts, sequential cohorts will be exposed to increasing doses of BT-11. In SAD, five doses will be evaluated, in MAD 3 dose levels will be evaluated.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2888 2888 0 0
/AnzctrAttachments/375350-ApprovalLetter-HREC2018-05-349.pdf

Contacts
Principal investigator
Name 84458 0
Dr Nicholas Farinola
Address 84458 0
CMAX
Level 5
18a North Terrace
Adelaide SA 5000
Country 84458 0
Australia
Phone 84458 0
+61 0870742823
Fax 84458 0
Email 84458 0
[email protected]
Contact person for public queries
Name 84459 0
Josep Bassaganya-Reira
Address 84459 0
Landos Biopharma
Josep Bassaganya-Reira
1800 Kraft Drive, Suite 216
Blacksburg, VA 24060 USA
Country 84459 0
United States of America
Phone 84459 0
+1 703-395-5034
Fax 84459 0
Email 84459 0
[email protected]
Contact person for scientific queries
Name 84460 0
Josep Bassaganya-Riera
Address 84460 0
Landos Biopharma
Josep Bassaganya-Reira
1800 Kraft Drive, Suite 216
Blacksburg, VA 24060 USA
Country 84460 0
United States of America
Phone 84460 0
+1 540-818-2844
Fax 84460 0
Email 84460 0
[email protected]

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

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

Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
4084Plain language summaryNo Overall, oral administration of BT-11 was generall... [More Details]
4713Conference abstractNo

Documents added automatically
No additional documents have been identified.