ANZCTR - Registration

Registration number

ACTRN12625001215415

Ethics application status

Approved

Date submitted

10/09/2025

Date registered

4/11/2025

Date last updated

9/10/2026

Date data sharing statement initially provided

4/11/2025

Type of registration

Prospectively registered

Titles & IDs

Public title

A study to assess safety, tolerability, and pharmacokinetics of RTX-010/101/111 in healthy adults. Part 1A and Part B healthy participants only

Scientific title

A Randomized, Placebo Controlled, Double-Blind, Single-Ascending Dose and Multiple-Ascending Dose First-in-Human Study to Investigate the Safety, Tolerability, and Pharmacokinetics, of Orally Administered RTX-010/101/111 in Healthy Adult Subjects

Additional trial identifiers [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Related trial records

Health condition

Health condition(s) studied:

Amyotrophic Lateral Sclerosis

Condition category

Condition code

Neurological

Neurodegenerative diseases

Intervention/exposure

Study type

Interventional

Description of the intervention or exposure

This is a first-in-human (FIH), multi-centre, double-blind, placebo-controlled, randomized, SAD, MAD study of RTX-101, RTX-010 and RTX-111 conducted in healthy adult participants and adult patients with C9orf72-ALS designed to evaluate the safety, tolerability, and PK of RTX-101, RTX-010 and RTX-111.

The treatments RTX-101 (comprises of 2 different medications), RTX-010 (is only 1 medication) and RTX-111 (comprises of 3 different medications, RTX-101 and RTX-010) are white opaque gelatine capsules.

There are 2 parts to the study:
Part 1 is known as Part 1A and
Part 2 is known as Part 1B.

In all cohorts of Part 1A (Single Ascending Dose - SAD) and Part 1B (Multiple Ascending Dose - MAD), the participants will register their interest in the study and the potential dates which are suitable for taking part in the study. The dates which are advised by the CMAX team will identify which cohort each participant will be taking part in.

Dosing in all cohorts of SAD and MAD will be administered orally. Participants will be instructed to swallow the capsule (s) whole and the site will check their mouth afterwards to ensure they have swallowed the capsule (s).

The commencement of dosing in SAD Arm A and SAD Arm B cohorts may overlap due to the safety of different study drugs being investigated

Part 1A: Single ascending dose (SAD) in healthy volunteers. Eight participants will be dosed in each cohort of Part 1A.
Part 1A Cohort 3 will have 2 periods where the same participants will take part in each period. SAD Cohort 3, Both periods in Cohort 3 will follow the same schedule as for Cohorts 1, 2, & 4, and that Period 2 will commence after a washout period of at least 14 days.

There will be a total of n= 64 participants dosed in Part 1A (SAD)

SAD Arm A: RTX-101 or placebo (3:1 Randomization Ratio) n= 32 participants will take part in Arm A
Cohort 1: Participants will receive oral doses of RTX-101 (1 x 500mg capsule and 1 x 300mg capsule) or placebo (1 x 500mg and 1 x 300mg capsule)
Cohort 2: Participants will receive oral doses of RTX-101 (2 x 500mg and 1 x 300mg capsule) or placebo (2 x 500mg and 1 x 300mg capsule)
Cohort 3: Participants will receive oral doses of Period 1 RTX-101 (4 x 500mg and 1 x 300mg capsule) or placebo (4 x 500mg and 1 x 300mg capsule)
Cohort 3: Participants will receive oral doses of Period 2 RTX-101 (4 x 500mg and 1 x 300mg capsule) or placebo (4 x 500mg and 1 x 300mg capsule) (mixed in apple-sauce),
Cohort 4: Participants will receive oral doses of RTX-101 (6 x 500mg and 1 x 300mg capsule) or placebo (6 x 500mg and 1 x 300mg capsule)

SAD Arm B: RTX-010 or Placebo (3:1 Randomisation Ratio) n= 24 participants will take part in Arm B.
Cohort 5: Participants will receive oral doses of RTX-010 100mg capsule or placebo 100mg capsule
Cohort 6: Participants will receive oral doses of RTX-010 200mg capsule or placebo 200mg capsule
Cohort 7: Participants will receive oral doses of RTX-010 400mg capsule or placebo 400mg capsule

SAD Arm C: RTX-111 (3:1 Randomization Ratio) n=8 participants will take part in Arm C.

Participants will receive oral doses of RTX-111 (6 x 500mg, 2 x 200mg and 1 x 300mg capsules) or placebo (6 x 500mg, 2 x 200mg and 1 x 300mg capsules).

Part 1B: Multiple ascending dose (MAD) in healthy volunteers. Dose once daily from Day 1 to Day 7. A total of n=32 participants will be dosed in Part 1B (MAD)

MAD Arm A: 16 participants will be dosed in this Arm
Participants will receive oral doses of RTX-101 or Placebo from Day 1 to Day 7 (3:1 Randomization Ratio)
Cohort 1: Participants will receive oral doses of RTX-101 (4 x 500mg and 1 x 300mg capsules) or placebo (4 x 500mg and 1 x 300mg capsules)
Cohort 2: Participants will receive oral doses of RTX-101 (4 x 500mg (2 x 500mg capsules administered twice daily) and 1 x 300mg (administered once daily) capsule) or placebo (4 x 500mg (2 x 500mg capsules administered twice daily) and 1 x 300mg (administered once daily) capsule)

MAD Arm B: 8 participants will be dosed in this Arm
Participants will receive oral doses of RTX-010 or Placebo from Day 1 to Day 7 (3:1 Randomization Ratio)
Cohort 3: Participants will receive oral doses of RTX-010 (2 x 200mg capsules) or placebo (2 x 200mg and capsules) once daily

MAD Arm C: n=16 participants will take part in this arm.
Participants will receive oral doses of RTX-111 or Placebo (3:1 Randomization Ratio)
Cohort 5: Participants will receive oral doses of RTX-111 (6 x 500mg (3 x 500mg administered twice daily) 2 x 200mg (administered once daily) and 1 x 300mg (administered once daily) capsule) or placebo (6 x 500mg (3 x 500mg administered twice daily) 2 x 200mg (administered once daily) and 1 x 300mg (administered once daily) )
Cohort 4: Participants will receive oral doses of RTX-111 (6 x 500mg (3 x 500mg administered twice daily) 2 x 200mg (administered once daily) and 2 x 100mg (administered once daily) capsule) or placebo (6 x 500mg (3 x 500mg administered twice daily) 2 x 200mg (administered once daily) and 1 x 300mg (administered once daily) )

Intervention code [1]

Treatment: Drugs

Description of the comparator or control

Part 1A (SAD):
In all SAD cohorts there will be n=6 participants who receive active treatment and n=2 who receive the placebo. Placebo looks the same as the active treatment (white opaque gelatine capsules) but doesn’t contain any study drug.
Part 1B (MAD)
In all MAD cohorts there will be n=6 participants who receive active treatment and n=2 who receive the placebo. Placebo looks the same as the active treatment but does not contain any study drug

Control group

Placebo

Outcomes

Primary outcome [1]

To investigate the safety and tolerability of the administration of RTX-101 in healthy adult participants following single and multiple ascending oral dose administrations.

Timepoint [1]

Part 1A: Cohort 3 assessments will be completed in both Period 1 and Period 2 Vital signs: Blood pressure (systolic and diastolic), heart rate, respiratory rate using a blood pressure cuff and temperature using a thermometer will be measured at screening, Day -1, Day 1 pre-dose, 1 hour, 3 hour, 6 hour, 8 hour, 12 hour, 24 hour (Day 2), 36 hour (Day 2), 48 hour (Day 3), 72 hour (Day 4) and Day 7. ECGs using an ECG machine will be measured at screening, Day -1, Day 1 pre-dose, 1 hour, 3 hour, 6 hour, 8 hour, 12 hour, 24 hour (Day 2), 48 hour (Day 3), 72 hour (Day 4) and Day 7. Safety Laboratory Tests (including biochemistry, haematology, coagulation and urinalysis - blood collected by either needle/syringe or cannula and urine sample will be collected at screening, Day -1, Day 1 pre-dose, 24 hour (Day 2), 72 hours Day 4 and Day 7. Part 1B: Vital signs: Blood pressure (systolic and diastolic), heart rate, respiratory rate using a blood pressure cuff and temperature using a thermometer will be measured at screening, Day -1, Day 1 and Day 7 pre-dose, 1.5 hour, 3 hour, 6 hour, 24 hour (Day 2), 48 hour (Day 3), 72 hour (Day 4), Day 5, Day 6, Day 8 and Day 14. If afternoon dosing occurs there are additional vital signs on Day 1 and 7 pre-afternoon dose, 1.5 hour, 3 hour and 6 hour. ECGs using an ECG machine will be measured at screening, Day -1, Day 1 and Day 7 pre-dose, 1 hour, 3 hour, 6 hour, 8 hour, 12 hour, 24 hour (Day 2), 72 hour (Day 4), Day 6, Day 8 and Day 14. If afternoon dosing occurs there are additional ECGs performed on Day 1 and Day 7 pre-afternoon dose, 1.5 hour, 3 hour and 6 hours. Safety Laboratory Tests (including biochemistry, haematology, coagulation and urinalysis - blood collected by either needle/syringe or cannula and urine sample will be collected at screening, Day -1, Day 1 pre-dose, 24 hour (Day 2), 72 hours Day 4, Day 6, Day 7, Day 8 and Day 14.

Primary outcome [2]

To investigate the safety and tolerability of the administration of RTX-111 in healthy adult participants following single and multiple ascending oral dose administrations.

Timepoint [2]

Part 1A: Cohort 3 assessments will be completed in both Period 1 and Period 2 Vital signs: Blood pressure (systolic and diastolic), heart rate, respiratory rate using a blood pressure cuff and temperature using a thermometer will be measured at screening, Day -1, Day 1 pre-dose, 1 hour, 3 hour, 6 hour, 8 hour, 12 hour, 24 hour (Day 2), 36 hour (Day 2), 48 hour (Day 3), 72 hour (Day 4) and Day 7. ECGs using an ECG machine will be measured at screening, Day -1, Day 1 pre-dose, 1 hour, 3 hour, 6 hour, 8 hour, 12 hour, 24 hour (Day 2), 48 hour (Day 3), 72 hour (Day 4) and Day 7. Safety Laboratory Tests (including biochemistry, haematology, coagulation and urinalysis - blood collected by either needle/syringe or cannula and urine sample will be collected at screening, Day -1, Day 1 pre-dose, 24 hour (Day 2), 72 hours Day 4 and Day 7. Part 1B: Vital signs: Blood pressure (systolic and diastolic), heart rate, respiratory rate using a blood pressure cuff and temperature using a thermometer will be measured at screening, Day -1, Day 1 and Day 7 pre-dose, 1.5 hour, 3 hour, 6 hour, 24 hour (Day 2), 48 hour (Day 3), 72 hour (Day 4), Day 5, Day 6, Day 8 and Day 14. If afternoon dosing occurs there are additional vital signs on Day 1 and 7 pre-afternoon dose, 1.5 hour, 3 hour and 6 hour. ECGs using an ECG machine will be measured at screening, Day -1, Day 1 and Day 7 pre-dose, 1 hour, 3 hour, 6 hour, 8 hour, 12 hour, 24 hour (Day 2), 72 hour (Day 4), Day 6, Day 8 and Day 14. If afternoon dosing occurs there are additional ECGs performed on Day 1 and Day 7 pre-afternoon dose, 1.5 hour, 3 hour and 6 hours. Safety Laboratory Tests (including biochemistry, haematology, coagulation and urinalysis - blood collected by either needle/syringe or cannula and urine sample will be collected at screening, Day -1, Day 1 pre-dose, 24 hour (Day 2), 72 hours Day 4, Day 6, Day 7, Day 8 and Day 14.

Primary outcome [3]

To investigate the safety and tolerability of the administration of RTX-010 in healthy adult participants following single and multiple ascending oral dose administrations.

Timepoint [3]

Part 1A: Cohort 3 assessments will be completed in both Period 1 and Period 2 Vital signs: Blood pressure (systolic and diastolic), heart rate, respiratory rate using a blood pressure cuff and temperature using a thermometer will be measured at screening, Day -1, Day 1 pre-dose, 1 hour, 3 hour, 6 hour, 8 hour, 12 hour, 24 hour (Day 2), 36 hour (Day 2), 48 hour (Day 3), 72 hour (Day 4) and Day 7. ECGs using an ECG machine will be measured at screening, Day -1, Day 1 pre-dose, 1 hour, 3 hour, 6 hour, 8 hour, 12 hour, 24 hour (Day 2), 48 hour (Day 3), 72 hour (Day 4) and Day 7. Safety Laboratory Tests (including biochemistry, haematology, coagulation and urinalysis - blood collected by either needle/syringe or cannula and urine sample will be collected at screening, Day -1, Day 1 pre-dose, 24 hour (Day 2), 72 hours Day 4 and Day 7. Part 1B: Vital signs: Blood pressure (systolic and diastolic), heart rate, respiratory rate using a blood pressure cuff and temperature using a thermometer will be measured at screening, Day -1, Day 1 and Day 7 pre-dose, 1.5 hour, 3 hour, 6 hour, 24 hour (Day 2), 48 hour (Day 3), 72 hour (Day 4), Day 5, Day 6, Day 8 and Day 14. If afternoon dosing occurs there are additional vital signs on Day 1 and 7 pre-afternoon dose, 1.5 hour, 3 hour and 6 hour. ECGs using an ECG machine will be measured at screening, Day -1, Day 1 and Day 7 pre-dose, 1 hour, 3 hour, 6 hour, 8 hour, 12 hour, 24 hour (Day 2), 72 hour (Day 4), Day 6, Day 8 and Day 14. If afternoon dosing occurs there are additional ECGs performed on Day 1 and Day 7 pre-afternoon dose, 1.5 hour, 3 hour and 6 hours. Safety Laboratory Tests (including biochemistry, haematology, coagulation and urinalysis - blood collected by either needle/syringe or cannula and urine sample will be collected at screening, Day -1, Day 1 pre-dose, 24 hour (Day 2), 72 hours Day 4, Day 6, Day 7, Day 8 and Day 14.

Secondary outcome [1]

To investigate the plasma pharmacokinetics (PK) characteristics of single ascending oral doses of RTX-101, RTX-010 and RTX-111 in healthy participants

Timepoint [1]

Part 1A: Cohort 3 assessments will be repeated in both Period 1 and Period 2 Blood PK samples are collected at Day 1 pre-dose, 30 minutes, 1 hour, 1.5 hour, 3 hour, 4 hour, 6 hour, 8 hour, 12 hour, 24 hour, 36 hour, 48 hour, 72 hour and Day 7. Urine PK collection: a single urine sample at pre-dose, Day 1: all urine samples within 0-4 hours, all urine samples within 4 to 12 hours, all urine samples within 12 to 24 hours, all urine samples within Day 2: 24 to 48 hours.

Secondary outcome [2]

To investigate the plasma pharmacokinetics (PK) characteristics of single ascending oral doses of RTX-101, RTX-010 and RTX-111 in healthy participants

Timepoint [2]

Part 1B Blood PK samples are collected at Day 1 pre-dose, 30 minutes, 1 hour, 1.5 hour, 3 hour, 4 hour, 6 hour, 8 hour, 12 hour, Day 2 to Day 6 pre-dose, Day 7 pre-dose, 30 minutes, 1 hour, 1.5 hour, 3 hour, 4 hour, 6 hour, 8 hour, 12 hour, 24 hour and Day 14. If afternoon dosing occurs there is an additional PK sample collected at 9.5 hours performed on Days 1 7. Urine PK collection: a single urine sample at pre-dose, Day 1: all urine samples within 0-4 hours, all urine samples within 4 to 12 hours, all urine samples within 12 to 24 hours, Day 2: all urine samples within 24 to 48 hours, Day 7: all urine samples within 0-4 hours, all urine samples within 4 to 12 hours, all urine samples within 12 to 18 hours and all urine samples within 18 to 24 hours.

Eligibility

Key inclusion criteria

1) Must be able to provide written, personally signed and dated informed consent to participate in the study in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations before completing any study related procedures.
2) Male or female ages 18 to 65 years, inclusive, at the time of consent.
3) Relatively good health as determined by the Investigator based on review of medical history, physical examination, ECG, vital signs, and clinical laboratory tests.
4) Body mass index (BMI) 18 to 35 kg/m2 inclusive (BMI = weight (kilograms)/(height [meters]2).
5) Non-smokers or tobacco/nicotine user (e.g., smokers, electronic cigarettes, vaping, and smokeless tobacco/nicotine products), that are willing to abstain from nicotine use throughout the study (Day-1 through End of Study Follow-up).
6) Females of childbearing potential must agree to use a highly effective method of contraception from the time of consent through at least 3 months after the last dose of study medication. Highly effective methods of contraception include: intrauterine device, intrauterine system, contraceptive implant, combined injectable contraceptives, hormonal oral contraceptives when used in combination with male condoms. Sexual abstinence, defined as refraining from intercourse, when this is in line with the preferred and usual lifestyle of the participant. Remain exclusively in a same sex relationship, when this is in line with the preferred and usual lifestyle of the participant. Female participants with male partner(s) must utilize highly effective forms of contraception and their male partner(s) must use a male condom. Female participants must refrain from donating ova from 3 months after administration of the last dose of study drug.
7) Females of nonchildbearing potential must be postmenopausal (defined as a minimum of 12 consecutive months of spontaneous amenorrhea) or surgically sterile (hysterectomy, bilateral oophorectomy, bilateral salpingectomy, bilateral tubal ligation or bilateral tubal occlusion). Females of nonchildbearing potential are exempt from contraception requirements.
8) Males who are sexually active and whose partners are females of childbearing potential must agree to use male condoms from the time of consent through 3 months after administration of the last dose of study drug, and their partners must be willing to use a highly effective method of contraception from screening through 3 months after administration of the last dose of study drug. Males must agree not to donate sperm from screening through 3 months after administration of the last dose of study drug.
9) Able to refrain from consuming xanthine containing beverages and food (e.g., coffee, tea, cola, energy drinks and dark chocolate) from 24 hours prior admission to the clinic until the End of Study visit.
10) Must refrain from intensive physical exercise from 48 hours prior admission to the clinic until the End of Study visit.
11) Must not take any prescription with the exception of contraceptives or over-the-counter medications, herbal remedies, or food supplements during the study unless otherwise approved by the Investigator.
12) Must be fluent in English and have a degree of understanding sufficient to communicate suitably with the Investigator and the study coordinator.-

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Healthy volunteers

Yes

Key exclusion criteria

1) Any of the following medical conditions:
a. Any active or serious medical condition which could interfere with the participant's safety during the trial,
b. History or presence in the past 5 years of gastrointestinal, hepatic or renal disease (eGFR , 75mL/min/1.73m2 or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs including Gilbert's syndrome or have undergone an cholecystectomy.
c. Positive tests for HIV, hepatitis B or hepatitis C.
d. Participants must not have a history of seizure disorder.
e. Previous malignant disease (except basal cell carcinoma of skin and cervical carcinoma in situ/dysplasia).
f. History of thyroid impairment or dysfunction and/or require medical intervention for thyroid impairment/dysfunction.
2) Must not have a history of organic heart disease including coronary artery disease, myocardial infarction, angina, clinically significant abnormal ECGs, QTcF interval > 450 msec for males and >470 msec for females, congestive heart failure, valvular heart disease and congenital heart disease.
3) Must not have screening or baseline: systolic blood pressure (SBP) > 139 mmHg, diastolic blood pressure (DBP) > 89 mmHg, and resting heart rate (HR) > 90 BPM. Vital signs may be repeated once at the Investigator’s discretion.
4) Known gout and/or treatment required gout and/or hyperuricemia (defined as serum uric acid above the upper limit of normal with physiologic consequences) identified at screening (or prior AM dosing on Day 1).
5) Use of concomitant medications that prolong the QT/QTc interval or triptan medications for migraine headaches.
6) Participants with abnormal iron storage including haemochromatosis or elevated serum ferritin levels that may lead to clinically significant outcomes in the opinion of the PI identified at screening (or prior to dosing).
7) Active primary psychiatric disorders based on the participant's medical history and and the Columbia Suicide-Severity Ranking Scale (C-SSRS) identified at screening or prior to dosing.
8) Psychiatric hospitalization within 12 months of screening date.
9) Must not have a history of moderate to severe substance use, or any other substance use disorder (excluding nicotine) currently or within one year prior to enrolment based on the discretion of the investigator.
10) Must not test positive for a substance of abuse or have a positive alcohol breath test at the time of screening or check in.
11) Must not have a history of, or current, dysphagia or other swallowing difficulties that, in the opinion of the investigator,
12) History of excessive daily consumption of caffeine containing drinks (i.e., > 400 mg/day of caffeine or 4-5 cans (300 ml to 355 ml) of cola beverages.
13) Positive pregnancy test at screening or check in or is breastfeeding/lactating.
14) Any history of drug or other significant allergy.
15) Symptoms or history suggestive of a recent systemic illness or febrile illness within 7 days prior to check in based on the Investigator’s discretion.
16) Donation of one or more units of blood within 60 days, plasma within 30 days prior to the screening or platelet donation within 60 days prior to screening.
17) Cannot tolerate venipuncture or has poor venous access
18) Use of any prescription medication (excluding contraceptives) within 7 days or 5 half-lives prior to admission to the clinic on Day -1 through the End of Study visit.
19) Use of over-the-counter medications, herbal and nutritional supplements including St. John’s Wort within 4 days or 5 half-lives prior to admission to the clinic on Day -2.
20) Has taken other investigational drug or participated in any clinical study 30 days prior to the dosing or is currently participating in another clinical study.
21) Clinically significant laboratory (blood or urine) abnormality as defined by the investigator. Liver enzymes (Total Bilirubin, AST/ALT, ALP, GGT) may not be greater than 1.5X the upper limit of normal (ULN) at baseline.
22) Unwilling or unlikely to comply with the requirements of the study.
23) Unable to commit to participating in the entire estimated 7 (±2 days) for Part 1A and (14 (±4) days for Part 1B of the trial

Study design

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

4/11/2025

Actual

28/11/2025

Date of last participant enrolment

Anticipated

24/11/2026

Actual

Date of last data collection

Anticipated

4/12/2026

Actual

Sample size

Target

102

Accrual to date

92

Final

Recruitment in Australia

Recruitment state(s)

SA

Recruitment hospital [1]

CMAX Clinical Research Pty Ltd - Adelaide

Recruitment postcode(s) [1]

5000 - Adelaide

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Repeat Therapeutics Pty Ltd

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Repeat Therapeutics Pty Ltd

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry Human Research Ethics Committee E

Ethics committee address [1]

https://bellberry.com.au/

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/09/2025

Approval date [1]

22/10/2025

Ethics approval number [1]

Summary

Brief summary

A Phase 1, First-in-Human, Single and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral administration of RTX-101, RTX-010 and RTX-111 in Healthy Subjects.

The current study is the first clinical co-administration of combinations of RTX-101, RTX-010 and RTX-111 to be conducted in healthy adult subjects. The study includes Part 1A: single ascending dose (SAD) and  Part 1B: multiple ascending dose (MAD).

Trial website

Public notes

Contacts

Principal investigator

Name

Dr James Connell

Address

CMAX Clinical Research 21/24 North Terrace Adelaide 5000 South Australia

Country

Australia

Phone

+61 0 421 018 611

Email

[email protected]

Contact person for public queries

Name

Susan Francia

Address

Repeat Therapeutics, Inc. is 5639 Dolphin Pl. La Jolla, CA 92037

Country

United States of America

Phone

+1 267 968 4355

Email

[email protected]

Contact person for scientific queries

Name

James Connell

Address

CMAX Clinical Research 21/24 North Terrace Adelaide 5000 South Australia

Country

Australia

Phone

+61 0 421 018 611

Email

[email protected]

Trial Review

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