FUNCtion-ALS

A Randomised Phase 1/2 Trial Aiming to Restore UNC13A Function in ALS (FUNCtion-ALS)

UK Chief Investigator

Professor Dame Pamela Shaw

Research summary

Amyotrophic Lateral Sclerosis (ALS) is a rare, progressive condition that makes a person’s muscles weaker over time. People living with ALS will continue to decline and may experience respiratory failure and death. Current treatments for pALS are riluzole and edaravone for a broader population, and tofersen for a small sub-population that have a known gene mutation called superoxide dismutase 1 (SOD1). The current treatments are not available in all countries and some treatments may not benefit those suffering from ALS, leaving an unmet need. This trial will test TRCN-1023, an unapproved treatment, to evaluate its safety and potential for treating adult people living with ALS.

This trial is designed to assess how safe TRCN-1023 is for people living with ALS, whether it causes side effects, how it works in people living with ALS, and how the body responds to the treatments. Also, the clinical trial is designed to assess whether TRCN-1023 can help people living with ALS with their condition.

To assess safety and any side effects, the clinical trial will monitor and evaluate the number and severity of adverse events (unintended, harmful, and/or undesirable outcomes) over a 24-week period. Blood and cerebral spinal fluid collected from participants in the clinical trial will be evaluated to determine how long it stays in the body after it is injected. The cerebral spinal fluid will also be evaluated to determine how TRCN-1023 works with the human body.

This is a randomised, double-blinded, placebo-controlled trial. A placebo-controlled trial means TRCN-1023 will be compared against a placebo (non-active substance). Participants will be randomly selected, by a computer, to be treated with either TRCN-1023 or placebo. A double-blind trial means that neither the participants nor the trial staff know who is receiving TRCN-1023 or placebo.

Current status

In setup

Recruitment target

3 participants in the UK; up to 30 participants globally

Recruitment groups

Patients with MND

Locations

• Sheffield, Principal Investigator: Johnathan Cooper-Knock.  In set-up, site opening soon

• London - University College London Hospital, Principal Investigator: .  In set-up, site opening soon

Information about study sites

Key dates

Planned recruitment open date: July 2026

Planned recruitment end date: 

Inclusion / exclusion criteria

Key Inclusion criteria

• Adults aged 18 to 75 years

• Diagnosis of ALS (clinically definite, clinically probable, or clinically probable laboratory supported)

• ALS symptoms began within the past 24 months

• Able to perform breathing tests: slow vital capacity (SVC) with consistent results, with breathing capacity of at least 60% of the expected value

• Able and willing to meet all study requirements, including travel to the study site, brain magnetic resonance imaging (MRI) scans, lumbar punctures, and blood draws

• Able and willing to use wearable sensors and complete speech assessments at home

• On a stable dose of approved ALS medication for at least 4 weeks prior to screening

• Capable of providing informed consent

Key Exclusion criteria

• Carries a confirmed SOD1 or FUS gene mutation

• Has a tracheostomy or requires continuous assisted ventilation more than 22 hours per day during the preceding 3 months before the first Screening Visit

• Has a contraindication to brain MRI (e.g., pacemaker, metal implants)

• Has a contraindication to lumbar puncture or spinal injection (e.g., blood clotting disorders, certain blood thinners, signs of increased pressure in the brain)

• Has significant abnormal liver, kidney, or blood test results

• Is currently enrolled in another clinical trial or has received an investigational treatment within the past 4 weeks

• Has previously received gene therapy, stem cell therapy, or another Antisense oligonucleotide (ASO) treatment

• Has a clinically significant condition other than ALS that could interfere with study participation

Funder & Sponsor

Trace Neuroscience, Inc.

Study design

Interventional; randomised, placebo-controlled trial

Intervention

• Study drug: TRCN-1023

• Placebo

Phase

1/2

Outcome measures

Primary outcome measure:

• Frequency of Adverse Events

Secondary outcome measures:

• Plasma concentrations of TRCN-1023

• CSF concentrations of TRCN-1023

• Time to Peak Plasma Concentration 

• Peak Plasma Concentration (Cmax) of TRCN-1023 

• Area Under the Plasma Concentration-Time Curve to Last Measurable Concentration (AUClast) of TRCN-1023