EXPERTS-ALS

The EXPErimental medicine Route To Success in ALS (EXPERTS-ALS)  

UK Chief Investigator

Professor Chris McDermott

Research summary

The EXPERTS-ALS platform trial is designed as a randomised, open-label, multi-arm trial with a biomarker-based endpoint. It aims to prioritise drugs for further testing based on their ability to lower NFL levels and to also identify drug-specific adverse events. The EXPERTS-ALS protocol describes an overarching trial design to evaluate the effect of candidate drugs on blood NFL levels in patients with ALS receiving usual standard of care. The protocol is deliberately flexible, allowing: as broad a range of ALS patients to be recruited; participant randomisation between only those treatment arms that are not believed by the enrolling doctor to be contraindicated (e.g. by particular co-morbid conditions or concomitant medications); and treatment arms to be added or removed according to the emerging evidence from within the trial. 

Current status

Open to recruitment

Recruitment target

700 participants

Recruitment groups

Patients with Amyotrophic Lateral Sclerosis (ALS), a type of MND

Locations

• Cambridge, Principal Investigator: Rhys Roberts. Site in set-up, opening soon

• Edinburgh, Principal Investigator: Suvankar Pal. Site open for local recruitment only

• Exeter, Principal Investigator: Tim Harrower. Site open for recruitment out-of-area

• Liverpool, Principal Investigator: Siva Sathasivam. Site in set-up, opening soon

• London - King's College Hospital, Principal Investigator: Ammar Al-Chalabi. Site open for recruitment out-of-area

• London - University College London, Principal Investigator: Andrea Malaspina. Site in set-up, opening soon

• Newcastle, Principal Investigator: Tim Williams. Site in set-up, opening soon

• Oxford, Principal Investigator: Martin Turner. Site open for local recruitment only

• Salford, Principal Investigator: Amina Chaouch. Site in set-up, opening soon

• Sheffield, Principal Investigator: Chris McDermott. Site open for local recruitment only

• South Wales MND Network, Principal Investigator: Tom Massey.  Site open for local recruitment (South Wales network) only

Information about study sites

Contact details

Email: experts-als@sheffield.ac.uk

Study website: https://www.experts-als.uk/

Key dates

Recruitment opening date: November 2024

Planned recruitment end date: 31 March 2028

Inclusion / exclusion criteria

Key inclusion criteria:

• Diagnosis of ALS according to Gold Coast criteria

• Age at least 18 at the time of consent

• ENCALS prognosis risk score of -6.0 to -2.0 as calculated from the results of the screening visit

• Those taking riluzole must be on a stable dose for at least 30 days prior to the baseline visit or must have chosen not to take it for the study duration

• Must be able to be randomised to at least two of the open arms after reviewing contraindications, current medication and the IMP-specific eligibility criteria as detailed in the IMP-specific appendices

• Fertile persons must use adequate contraception if required by the IMPs

• Persons of childbearing potential must have a negative pregnancy test prior to randomisation.

Key exclusion criteria:

• Clinically significant history of unstable or severe cardiac, oncological, hepatic or renal disease or other medically significant illness which, in the opinion of the local investigator, is a contraindication to participation

• Presence of an active disorder (other than ALS) which is known to independently raise NFL levels

• Participation in any other investigational drug trial within 30 days prior to screening

• Pre-existing use of current EXPERTS-ALS IMPs or drugs in the same class as current EXPERTS-ALS IMPs that would result in the patient not being able to be randomised between a minimum of two arms

• Contraindications to IMPs that would result in the patient not being able to be randomised between a minimum of two arms

• Use of non-invasive ventilation >22 hr/day or tracheostomy ventilation

• Pregnant or breastfeeding

• Unable to comply with trial procedures. 

Funder

National Institute for Health and Care Research, Efficacy and Mechanism Evaluation (NIHR EME)

Sponsor

Sheffield Teaching Hospitals NHS Foundation Trust

Study design

Interventional, open-label, randomised drug prioritisation platform trial

Intervention

• Drug: Metformin

• Drug: Nifedipine

• Drug: Ropinirole 

Phase

2

Outcome measures

Primary outcome measure:

Change in blood neurofilament light chain (NfL) levels measured using automated immunoassay analysed via the SIMOA HD-X instrument (Quanterix) from baseline to weeks 18 and 24.

Secondary outcome measures:

1. Change in daily functioning measured using the ALS revised functional rating scale (ALSFRS-R) score from baseline to weeks 12 and 24.

2. Progression in the clinical stage by 1 stage or more measured using King’s staging system from baseline to week 24.

3. Adverse events and serious adverse events measured using data recorded at each study visit during the trial.

Exploratory outcomes:

1. Survival without tracheostomy or non-invasive ventilation at 12 months, compared with the ENCALS median prediction of survival without tracheostomy or non-invasive ventilation.

2. Change in WHO Disability Assessment Schedule (WHODAS 2.0) and Quality of Life (WHOQOL-Bref) from baseline to 24 weeks (or early discontinuation of treatment) against a natural history cohort.

3. In-person forced vital capacity (FVC) and peak cough flow (PCF), compared with remote FVC (rFVC) and remote PCF (rPCF) where readings are available within +/- 7 days of each other (FVC and PCF measured at screening, baseline, week 12 and week 24 post randomisation).