None listed
Conditions
Brief summary
This is a Phase II, open-label, multicentre study evaluating the safety, tolerability, pharmacokinetics, and activity of SIR2501 in participants with amyotrophic lateral sclerosis (ALS) and in participants with solid tumours receiving paclitaxel chemotherapy to prevent or reduce chemotherapy-induced peripheral neuropathy (CIPN). The study consists of a dose-escalation component (Part A) and an expansion component (Part B). Approximately 88 participants will be enrolled across both study parts. The primary objective is to assess safety and tolerability of SIR2501, with secondary objectives including pharmacokinetic evaluation and preliminary efficacy assessments. Participants will receive study treatment and will be followed according to protocol-defined schedules for safety and outcome evaluation. This study aims to evaluate the safety, tolerability, pharmacokinetics, and activity of SIR2501 in participants with amyotrophic lateral sclerosis (ALS) and in participants with solid tumours receiving paclitaxel chemotherapy to prevent or reduce chemotherapy-induced peripheral neuropathy (CIPN). Who is it for? You may be eligible for this study if you are a male or female aged 18–70 years with a diagnosis of amyotrophic lateral sclerosis (ALS), or aged 18–75 years with a diagnosis of a solid tumour receiving paclitaxel-based chemotherapy and at risk of developing chemotherapy-induced peripheral neuropathy. Study details For those who choose to enrol in this study, they will take the study medicine SIR2501 by mouth once daily. Part A (dose escalation): Participants will receive increasing dose levels of SIR2501 (30 mg, 45 mg, or 60 mg) to determine the safest dose and the recommended dose for further study. Part B (dose expansion): Participants will receive SIR2501 at the selected dose to further evaluate safety, tolerability, pharmacokinetics, and activity. Participants with ALS will receive treatment for up to 24 weeks. Participants receiving paclitaxel chemotherapy will receive treatment for approximately 12–18 weeks. During the study, participants will attend regular clinic visits where assessments may include physical examinations, questionnaires, blood tests, pharmacokinetic (PK) blood sampling to measure drug levels, safety laboratory tests, and monitoring for any side effects. It is hoped that the results of this study will help determine whether SIR2501 is safe and may provide benefit for people with ALS and for people receiving chemotherapy who are at risk of developing peripheral neuropathy.
Interventions
SIR2501 is an orally administered investigational small molecule.
This is a Phase Ib/IIa, open-label, multisite study conducted in two parts:
Part A (dose escalation):
Participants will receive SIR2501 orally once daily at escalating dose levels (30 mg, 45 mg, or 60 mg) using a standard 3+3 design to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).
Part B (dose expansion):
Participants will receive SIR2501 orally once daily at the selected dose to further eva
SIR2501 is an orally administered investigational small molecule. This is a Phase Ib/IIa, open-label, multisite study conducted in two parts: Part A (dose escalation): Participants will receive SIR2501 orally once daily at escalating dose levels (30 mg, 45 mg, or 60 mg) using a standard 3+3 design to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Part B (dose expansion): Participants will receive SIR2501 orally once daily at the selected dose to further evaluate safety, tolerability, pharmacokinetics, and activity. Participants with ALS will receive treatment for 24 weeks. Participants receiving paclitaxel-based chemotherapy will receive treatment for approximately 12–18 weeks. Study Structure (Parts A and B): This is a Phase Ib/IIa, open-label, two-part study including two independent patient populations: Participants with ALS, and Solid tumour participants receiving paclitaxel-based chemotherapy and at risk of CIPN. Both ALS and CIPN populations will participate in Part A (dose escalation) and Part B (dose expansion); however, they are treated as separate cohorts throughout. Participants enrolled in Part A will not automatically continue into Part B. Part B will enrol separate participants following determination of the RP2D in Part A. The ALS and CIPN cohorts are analysed independently and will not be compared to each other in either Part A or Part B.
Sponsors
Sironax, Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
For ALS cohort: Adults aged 18–70 years Diagnosis of amyotrophic lateral sclerosis (ALS) Able to provide informed consent For CIPN cohort: Adults aged 18–75 years Diagnosis of a solid tumour receiving paclitaxel-based chemotherapy At risk of developing chemotherapy-induced peripheral neuropathy Able to provide informed consent
Exclusion criteria
Significant uncontrolled medical conditions Known hypersensitivity to study drug components Participation in another interventional clinical trial Any condition that, in the investigator’s opinion, would make participation unsafe
Outcome results
None listed