A study to assess safety, tolerability and pharmacokinetics of RTX-010/101/111 for participants with C9orf72-mediated Amyotrophic Lateral Sclerosis (ALS). Part 1C adults with C9orf72-mediated ALS only.
A Randomised, Open-Label, Multiple Dosing Study to assess safety, tolerability and pharmacokinetics of RTX-010/101/111 for participants with C9orf72-mediated Amyotrophic Lateral Sclerosis (ALS). Part 1C adults with C9orf72-mediated ALS only.
Repeat Therapeutics Pty Ltd
16 participants
May 1, 2026
Interventional
Conditions
Summary
A Phase 1 study, multiple dosing to evaluate the safety, tolerability and pharmacokinetics of oral administration of RTX-101 and RTX-111 in participants with C9orf72 ALS. The study is the first clinical administration of combinations of RTX-101 and RTX-111 to be conducted in participants with C9orf72 ALS. This study includes Part 1C: open-label treatment for participants with C9orf72 ALS.
Eligibility
Inclusion Criteria20
- Male or female patients, aged 18-70 years of age with definite or clinically probable sporadic or familiar ALS
- Documented pathological repeat expansions in the intronic hexanucleotide repeat found in open reading frame 72 on chromosome 9 (C9orf72).
- Time since first symptoms onset of ALS should be within 24-months at the time of screening
- Not taking riluzole (or other disease modifying medication) or on a stable dose of riluzole (or other disease modifying medication) for at least 4 weeks prior to the screening visit; subjects are not allowed to start taking riluzole (or other disease modifying medication) during the study.
- Capable of providing informed consent. Each participant must sign an ICF indicating that he or she understands the purpose of procedures required for the trial and is willing to
- participate in the trial. Consent is to be obtained prior to the initiation of any trial-related tests or procedures that are not part of standard-of-care for the participant’s disease.
- Capable and willing to undergo and follow trial procedures including visits to the trial clinic and visit requirements; in addition, must be willing and able to adhere to the prohibitions and restrictions specified in this protocol or has a competent caregiver/support person who can and will be able to support the individual's participation in the study, including assisting with the administration of study drug.
- 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 either utilize highly effective forms of contraception or their male partner(s)
- must use a male condom.
- Females of nonchildbearing potential must be postmenopausal (defined as a minimum of 12 consecutive months of spontaneous amenorrhea) or surgically sterile (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation). Females of nonchildbearing potential are exempt from contraception requirements.
- 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.
- Must be fluent in English and have a degree of understanding sufficient to communicate
- suitably with the Investigator and the study coordinator.
Exclusion Criteria38
- Known gout and/or treatment required gout and hyperuricaemia (defined as serum Uric Acid above the upper limit of normal with physiologic consequences).
- Presence of tracheostomy or chronic mechanical ventilation (Note: Non-invasive ventilation such as CPAP and BiPAP are allowed).
- Lung function – Slow Vital capacity (SVC) less than 60% at the time of screening.
- History of known allergy to allopurinol, inosine or guanosine.
- Hypersensitivity or known intolerance Inosine, or Guanosine or its excipients.
- Known hypersensitivity or contraindication to allopurinol or any of its excipients (e.g., rash,
- eosinophilia, liver enzyme elevation, or prior diagnosis of allopurinol hypersensitivity
- syndrome).
- Renal insufficiency as defined by eGFR =60 mL/min/1.73m^2 (obtained at screening).
- Pregnant women (confirmed by a pregnancy test within 7 days of first dose (Day 1)) or
- women currently breastfeeding.
- History of Class III/IV heart failure (per New York Heart Association - NYHA) at screening.
- Presence of unstable psychiatric disease as judge by the investigator.
- Evidence of suicide risk, defined as 1) suicide attempt within 1 year prior to screening visit
- or 2) significant risk judged by the Investigator and the CSSRS.
- Clinically significant unstable medical condition (other than ALS) (e.g., cardiovascular
- instability, systemic infection, untreated thyroid dysfunction, severe laboratory test anomaly
- or clinically significant electrocardiogram [ECG] changes) that would pose a risk to the
- participant if he/she were to participate in the trial, according to Investigator judgment.
- Patients 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 any time prior to dosing)..
- Currently enrolled in another interventional trial.
- Currently or previously treated within the last 14 days or planned exposure to any
- medications listed in Section 4.4.1 of the protocol.
- History of positive test result for human immunodeficiency virus or hepatitis C virus
- Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg]
- and/or hepatitis B core antibody [HBcAb]). Participants with immunity to hepatitis B from
- previous natural infection (defined as negative HBsAg, positive hepatitis B surface antibody
- immunoglobulin G, and positive HBcAb) or vaccination (defined as positive anti-HBs) are
- eligible to participate in the trial.
- Exclusionary safety laboratory values at screening:
- a. Alanine aminotransferase (ALT) >3 × upper limit of normal (ULN)
- b. Aspartate aminotransferase (AST) >3 × ULN
- c. Total bilirubin >3 × ULN
- d. Alkaline phosphatase (ALP) >3 × ULN
- e. Creatinine >1.5 × ULN
- f. Platelet count < 100,000/mm3
- g. Prothrombin time (PT) >1.2 x ULN
- h. Partial thromboplastin time (PTT) >1.2 × ULN
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Interventions
This is a multi-centre, open-label, randomized, multiple dosing of RTX-101 and RTX-111 conducted in adult participants with C9orf72-mediated Amyotrophic Lateral Sclerosis (ALS) designed to evaluate the safety, tolerability and PK of RTX-101 and RTX-111. The treatments RTX-101 (comprised of 2 different medications) and RTX-111 (comprised of 3 different medications). All medications are white opaque gelatine capsules. This part if the study is known as Part 1C. In Part 1C, the participating clinical sites will contact participants (who are attending/registered at the clinic) diagnosed with C9orf72 ALS who would be considered eligible based on their medical history and study inclusion/exclusion criteria to determine if the participant may be interested in participating in the study. The screening and observational period may commence whilst Part 1A and Part 1B for healthy participants component of the study is being conducted. The administration of RTX-101 and RTX-111 will be oral. The participants will be instructed to swallow the capsules whole and where applicable the clinical site/nursing staff will check their mouth afterwards to ensure they have swallowed the capsules. In cases where swallowing whole capsules may be difficult an alternative option may be provided. Part 1C has 2 arms (Arm A and Arm B), participants will be randomised to either of these 2 arms. There will be a total of 16 participants to be enrolled into the 2 arms in Part 1C Arm A: 8 participants will be randomised to RTX-101 treatment (comprised of 2 different medications). RTX-101 dosage to be determined based on Part 1A and Part 1B cohorts in healthy participants. There is a Safety Review Committee who will review all the data to determine the levels. There will only be one dose level for each of the 2 formulations in Arm A. The minimum dose is 1 x 500mg capsule and 1 x 300mg capsule and maximum dose is 6 x 500mg capsules and 1 x 300mg capsule. Arm B: 8 participants randomised RTX-111 treatment (comprised of 3 different medications). RTX-111 dosage to be determined based on Part 1A and Part 1B cohorts in healthy participants. There is a Safety Review Committee who will review all the data to determine the levels. There will only be one dose level for each of the 3 formulations in Arm B. The minimum dose is 1 x 500mg capsule, 1 x 100mg capsule and 1 x 300mg capsule and maximum dose is 6 x 500mg capsules, 2 x 200mg capsules and 1 x 300mg capsule. Participants will administer their allocated treatment once daily for approximately 6 months.
Locations(1)
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ACTRN12626000385347