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Trial registered on ANZCTR


Registration number
ACTRN12620000910909
Ethics application status
Approved
Date submitted
15/07/2020
Date registered
14/09/2020
Date last updated
14/09/2020
Date data sharing statement initially provided
14/09/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I Clinical Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single- and Multiple-Ascending Doses of RS1805 Tablets in Healthy Adult Subjects
Scientific title
A Phase I, Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single- and Multiple-Ascending Doses of RS1805 Tablets in Healthy Adult Subjects
Secondary ID [1] 301747 0
'Nil known'
Universal Trial Number (UTN)
Trial acronym
N/A
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Inflammatory Bowel Disease 318204 0
Condition category
Condition code
Oral and Gastrointestinal 316210 316210 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part 1 (Single Ascending Dose)
Lowest starting dose of 50 mg RS1805 tablets, and the dose level will be gradually escalated. The maximum dose in the single ascending-dose part is planned to be 600 mg RS1805 tablets administered orally. The intervention drug will be administered once only. It is planned to enroll 40 healthy adult subjects in Australia. Part 1 includes a total of 5 cohorts. There are 8 subjects in each cohort, including 6 subjects in the study drug (RS1805 tablets) group and 2 subjects in the placebo group, male or female subjects. The first cohort is randomized to receive 50 mg RS1805 tablets or placebo in a 3:1 ratio. The second cohort is randomized to receive 100 mg RS1805 tablets or placebo in a 3:1 ratio. The third cohort is randomized to receive 200 mg RS1805 tablets or placebo in a 3:1 ratio. The fourth cohort is randomized to receive 400 mg RS1805 tablets or placebo in a 3:1 ratio. The fifth cohort is randomized to receive 600 mg RS1805 tablets or placebo in a 3:1 ratio

Part 2 (Multiple Ascending Dose)
Starting dose of 100 mg RS1805 tablets, and the dose level will be gradually escalated. The maximum dose in the multiple ascending-dose part is planned to be 400 mg RS1805 tablets administered orally. The intervention drug will be administered daily for 7 days. It is planned to enroll 24 healthy adult subjects in Australia. Part 2 includes a total of 3 cohorts. There are 8 subjects in each cohort, including 6 subjects in the study drug (RS1805 tablets) group and 2 subjects in the placebo group, male or female subjects. The first cohort is randomized to receive 100 mg (tentative, to be confirmed after review of Part 1 data) RS1805 tablets or placebo in a 3:1 ratio. The second cohort is randomized to receive 200 mg (tentative, to be confirmed after review of Part 1 data) RS1805 tablets or placebo in a 3:1 ratio. The third cohort is randomized to receive 400 mg (tentative, to be confirmed after review of Part 1 data) RS1805 tablets or placebo in a 3:1 ratio.

A SRC Meeting is yet to occur before proceeding to Part 2 and is separated by 26 days.
Intervention code [1] 318041 0
Treatment: Drugs
Intervention code [2] 318042 0
Prevention
Comparator / control treatment
Placebo (microcrystalline cellulose PH102)
Control group
Placebo

Outcomes
Primary outcome [1] 324398 0
Safety and tolerability outcomes based on review of AEs, vital signs, ECGs, laboratory findings and physical exams

Common AEs were nasopharyngitis and headache.
Timepoint [1] 324398 0
AEs will be collected from the time of signing the informed consent form until the last follow-up is collected

Samples to be collected for the laboratory tests include blood, urine and faecal samples.

SAD Timepoints
Vital signs- are measured 0.5 h before and 2, 4, 12 and 24 h after single dosing on Day 1. Vital signs should be measured with an interval of at least 15 mins before ECG examination on D1, D2 and D4-D11, and vital signs can be measured at anytime on D3, D12 and D13.
ECGs- D1- Pre-dose, 30 minutes, 1 hour, 1.5, 2, 3, 4, 6, 8, 10, 12. Day 2, Day 3, Day 4 and Day 5
Laboratory findings- screening, baseline, Day 1, Day 2, Day 7 and early withdrawal
Physical exams- screening, Day 1, Day 7 and early withdrawal

MAD Timepoints
Vital signs- are measured 0.5 h before and 2, 4, 12 and 24 h after single dosing on Day 1. Vital signs should be measured with an interval of at least 15 mins before ECG examination on D1, D2 and D4-D11, and vital signs can be measured at anytime on D3, D12 and D13
ECG- D1- Pre-dose, 30 minutes, 1 hour, 1.5, 2, 3, 4, 6, 8, 10, 12. Day 2, Day 3, Day 4 and Day 5, Day 7, Day 8, Day 9, Day 10, Day 11
Secondary outcome [1] 384552 0
Plasma concentrations and PK parameters of RS1805 and its major metabolite SHR177414 after a single oral dose, including but not limited to: AUC, CMAX, Tmax, CL/F Vz/F and t1/2.
Timepoint [1] 384552 0
Part 1 (Singe Ascending Dose)
PK- Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 hours on Day 1 post dose
PD- pre-dose, 1, 2, 3, 4, 6 hours on Day 1 post dose

Secondary outcome [2] 385782 0
Change in downstream IL-17A caused by inhibition of ROR-gamma by RS1805 after a single oral dose
Timepoint [2] 385782 0
Part 2 (Multiple Ascending Dose)
PK- D1 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 hours, 12 hours on Day 1 post dose. Day 7- 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 hours, 12 hours post dose

PD- D1 Pre-dose, 1, 2, 4, 6 hours post dose on Day 1, D7- pre-dose, 1, 2, 4, 6 post dose

Eligibility
Key inclusion criteria
Healthy adult subjects, male or female, 18 to 55 years of age (inclusive) at the time of informed consent.
Subject with body mass index (BMI equal to weight/height squared) between 18 and 32 kg/m2 (inclusive), male equals to 50 kg and female equals to 48 kg.

Good overall health at screening based on the results of medical history, physical examination, vital signs, laboratory tests, 12-lead ECG, and chest radiography at screening.

All women of childbearing potential and all men with female partners of childbearing potential must use effective contraception method throughout the study, and for 1 month after the last dose.

Subjects understand and comply with the study requirements, voluntarily participate in this trial, and sign the written informed consent form
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Suspected allergy to the study drug or any component of the study drug, or allergic constitution

History of malignant tumor; with the exception of subjects with non-melanoma skin cancer that was cured > 2 years ago and cervical intraepithelial neoplasia that was cured > 5 years ago.

Subjects have any surgical operation within 3 months prior to screening, or subjects have not recovered from prior surgery as judged by investigators, or plan to receive the operation during the study and within 1 month after completing all study visits

History of clinical major heart disease, liver disease, nerve disease, respiratory disease, blood disease, digestive disease, immune disease, kidney disease or mental disease, which is considered by the investigator to confuse the study results or affect absorption, distribution, metabolism and excretion of drug or place the subjects at improper risks

Any disease that affects drug absorption, distribution, metabolism and excretion as judged by the investigator (e.g., gastrointestinal dysfunction, peptic ulcer, gastrointestinal surgery, etc.);

Active tuberculosis indicated by clinical symptoms, signs, laboratory tests or chest X-ray; latent tuberculosis indicated by T-spot or Quanti-FERON TB test

Investigator-judged clinically significant infections within 1 month prior to screening, including acute and chronic infections such as abscess, furuncle, carbuncle and other local infections, respiratory tract infections, urinary and reproductive infections, systemic infections, etc. Minor skin or respiratory infections that have completely resolved even within 1 month are acceptable at the discretion of the investigator

Participation in any clinical trial of drug or medical device within 3 months prior to screening (or 5 half-lives of drug, whichever is longer);

Any acute disease with clinical significance as judged by the investigator within 1 month prior to screening

Subjects who cannot discontinue CYP3A inducers or CYP3A inhibitors 14 days prior to baseline visit and during the study

Subjects who have received any live vaccine within 1 month prior to screening or need to receive live vaccine during the study (including 30 days after the last dose of study drug);

Use of prescription drug within 14 days prior to baseline and during the study, with the exception of hormonal contraception, topical medications at the discretion of the investigator, brief use of medications for non-exclusionary conditions that are not expected to interfere with safety or data quality at the discretion of the Principal Investigator and Sponsor

Use of over-the-counter drugs, including natural health products (e.g., food supplements and herbal supplements) within 14 days prior to baseline, with the exception of occasional use of paracetamol (up to 2 g daily), ibuprofen, or regular doses of vitamins

QTc greater than 450 ms or other significant ECG abnormalities with clinically significance as judged by the investigator.

White blood cell count, neutrophil count, lymphocyte count or hemoglobin in hematology exceed the normal reference range and is judged as clinically significant by the investigator.

Alanine aminotransferase (ALT) > 1.5 times the upper limit of normal (ULN) and/or aspartate aminotransferase (AST) > 1.5 times ULN and/or bilirubin > 1.5 times ULN;

Estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m² calculated by the Modification of Diet in Renal Disease (MDRD)

Patients who are positive for hepatitis B surface antigen, hepatitis B e antigen, antihepatitis C virus antibody, syphilis antibody, or HIV antibody.

Other laboratory test results exceed the laboratory normal reference range, based on which the investigator determines that the subject is not suitable to participate in this study. General conditions:

Subjects who plan to have a child or donate sperm during the study or within 90 days after the last dose of study drug.

Smokers: An average daily smoking of more than 5 cigarettes (or other nicotine containing products) at the time of screening.

Drinkers: Positive breath alcohol test (positive with equals to 0 mg/dl) at screening; or long-term fixed alcohol consumption within 3 months prior to screening, the subject drinks more than 14 units of alcohol per week, [1 unit equals to150 mL of wine, rice wine or low-grade liquor, 360 mL of beer, or 45 mL of high-grade (greater than 40 degrees) liquor];

Drug abusers: Positive in urine drug screening test.

Women who are pregnant or breastfeeding



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)
1. Randomisation Allocation
2. Sealed envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Use of randomisation allocation worksheet provided by statistician
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Detailed methodology for summarization and statistical analysis of data collected in this study will be included in the Statistical Analysis Plan (SAP), which will be retained by Reistone Biopharma/designated CRO. Appropriate modifications may be made in the SAP for plans identified in the protocol. However, any significant modifications to the definition and analysis of the primary study endpoint should also be reflected in the protocol amendment. The study results mainly adopt statistical description method. Unless otherwise specified, continuous endpoints are generally statistically described using number of cases, mean, standard deviation, median, minimum and maximum. Binary endpoints are generally described by number and percentage. PK endpoints (plasma concentrations and parameters) will be summarized using geometric mean, geometric coefficient of variation, mean, standard deviation, median, maximum, minimum, etc. Demographic and baseline characteristics will be statistically described and tabulated.

Recruitment
Recruitment status
Recruiting
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)
VIC
Recruitment hospital [1] 17051 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 30722 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 22733 0
China
State/province [1] 22733 0

Funding & Sponsors
Funding source category [1] 306179 0
Commercial sector/Industry
Name [1] 306179 0
Atridia Pty Ltd
Address [1] 306179 0
Suite 2.02, Level 2, 46 Market Street
Sydney, NSW 2000, Australia
Country [1] 306179 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Atridia Pty Ltd
Address
Suite 2.02, Level 2, 46 Market Street
Sydney, NSW 2000, Australia
Country
Australia
Secondary sponsor category [1] 306652 0
None
Name [1] 306652 0
Address [1] 306652 0
Country [1] 306652 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306392 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 306392 0
55 Commercial Road, Melbourne 3004 VIC
Ethics committee country [1] 306392 0
Australia
Date submitted for ethics approval [1] 306392 0
01/07/2020
Approval date [1] 306392 0
05/08/2020
Ethics approval number [1] 306392 0

Summary
Brief summary
Reistone Biopharma Co., Ltd is developing the study drug RS1805 as a potential new treatment for a condition called inflammatory bowel disease (IBD).

Inflammatory bowel disease (IBD) is a common chronic inflammatory disease affecting the gastrointestinal tract. It is characterized by abdominal pain, abdominal distension, diarrhea, vomiting, and weight loss. People with Inflammatory bowel disease (IBD) usually require lifelong medical treatment and selective surgery according to the severity of condition

The study drug, RS1805, is designed to moderate the activity of a specific protein found in the body called ROR-gamma. ROR-gamma can cause inflammation which lead to the symptoms experienced in patients with IBD. It is hoped by blocking the activity of ROR, symptoms associated with IBD may improve.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103722 0
Dr Ben Snyder
Address 103722 0
Dr Ben Snyder
Nucleus Network'
5th Floor, Burnet Tower, AMREP Precinct,
89 Commercial Road, Melbourne, Victoria 3004, Australia
Country 103722 0
Australia
Phone 103722 0
+61 3 3593 9817
Fax 103722 0
+61 (03) 9076 8911
Email 103722 0
b.snyder@nucleusnetwork.com.au
Contact person for public queries
Name 103723 0
Miss Raina Patel
Address 103723 0
Reistone Biopharma
29-126 to 129 Floor
1 Lincoln Street
Massachusetts, USA MA 01001
Country 103723 0
United States of America
Phone 103723 0
+1630 6777246
Fax 103723 0
Email 103723 0
raina.patel@reistonebio.com
Contact person for scientific queries
Name 103724 0
Dr Ben Snyder
Address 103724 0
Dr Ben Snyder
Nucleus Network 5th Floor, Burnet Tower, AMREP Precinct
89 Commercial Road, Melbourne, Victoria 3004, Australia
Country 103724 0
Australia
Phone 103724 0
+61 3 3593 9817
Fax 103724 0
+61 (03) 9076 8911
Email 103724 0
b.snyder@nucleusnetwork.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results