Bringing an ALS trial home – How far can you actually go?

A few weeks ago, I wrote about bringing a Duchenne trial home and how far the Home Trial Support model can take you when almost every drug is an injection. A number of readers asked me to do the same for ALS (amyotrophic lateral sclerosis).

ALS turns out to be an even more compelling design problem. Why? Because the drug doesn’t come in just one shape – it comes in three, and each one shifts the line between site and home visits to a completely different place.

A quick note on methodology: The definitions and illustrative schedules below reflect an internal template built from published trials and our practical delivery experience at MRN, rather than a single specific sponsor protocol. The goal is to highlight how study design shifts by route of administration.

A busy pipeline: Why the route is everything

There are dozens of products in clinical development for ALS across antisense and gene therapies, small molecules, stem-cell approaches, and anti-neuroinflammatory agents.

As a protocol designer, I care less about the mechanism of drug action and more about two practical variables:

• The route of administration
• The clinical aspects of efficacy and safety assessments

Together, these two factors dictate how much of a trial can operate in a hybrid home-and-site model. From a design perspective, the field splits cleanly into three categories:

• Oral Drugs (Largest Group): Includes pridopidine, several NLRP3 and kinase programs, repurposing baskets, and approved oral treatments like riluzole and oral edaravone. Nothing about an oral drug ties the patient to a site.
• Intravenous (IV) Drugs: Led by original formulation IV edaravone.
• Intrathecal Drugs: Genetically targeted antisense and gene therapies (such as tofersen for SOD1, alongside clinical programs from Regeneron, Trace, and Leal) administered via lumbar puncture.

High Competition for a Short Patient Window

Behind this pipeline sits an enormous amount of operational activity:

• 700+ total interventional ALS studies on ClinicalTrials.gov
• ~190 actively underway
• ~110 actively recruiting
• ~24 Phase 2 or 3 drug trials competing head-to-head for the exact same patient population

This represents roughly twice as many active trials as we see in Duchenne. While the absolute patient population is larger, ALS patients today have treatment options that can rapidly move them into therapies excluded by protocol. This makes the window for trial recruitment exceptionally tight.

Which trial elements suit a home setting?

If we isolate the routine efficacy and safety assessments from drug administration and evaluate them through our standard trial toolkit, a clear pattern emerges:

Home-Deliverable Assessments (via standard trained nurse visits):

• Functional Rating Scale (ALSFRS-R)
• Breathing tests (Slow Vital Capacity)
• Muscle strength & hand-held dynamometry
• Blood draws (including plasma neurofilament)
• Quality-of-life / PRO questionnaires
• Cognitive screening (ECAS)
• Adverse event & concomitant medication reviews

Site-Required Elements:

• Initial consent, eligibility, and safety-anchored baseline management
• Periodic investigator neurological examinations

Because the standard four-weekly workload of an ALS trial is heavily assessment-based, these studies are inherently strong candidates for home management. What ultimately changes the ratio of site to home visits is the route of administration (IP).

How drug route dictates the final trial shape

1. Oral Route

Visit Split: ~5 Site Visits / ~9 Home Visits (out of 14 visits)

Execution: Cleanest decentralized setup. Patients self-administer at home; visits are driven purely by safety and neuro exams. Dramatically reduces trial burden, boosting recruitment and retention.

2. Intravenous (IV) Route

Visit Split: ~8 Site Visits / ~6 Home Visits

Execution: Infusions are built into home visits. We recommend conducting the first 3 doses at the site to monitor for potential infusion reactions. Once tolerability is established, delivery transitions to the home. For intense regimens like edaravone (10–14 infusions per 28-day cycle), home delivery becomes crucial.

3. Intrathecal Route

Visit Split: Hybrid (Local Clinic + Home)

Execution: Requires a lumbar puncture. However, a lumbar puncture does not require a national centre of excellence – it can be performed locally by any competent neurologist in a clean room or local MRN site, while all supporting assessments take place in the home.

What a Visit Costs the Patient in Hours

To understand why local administration matters, consider the time breakdown of a full intrathecal dosing visit:

The Strategic Choice:

1. Centres of Excellence model: Forcing patients (who are progressively losing mobility and respiratory function) to travel long distances monthly for a 4–5 hour visit. High risk of poor enrollment for anyone living >20 miles away.
2. Decentralised / Local model: The 90-minute procedure is handled at a local clinic/MRN site, while full assessment battery visits are delivered in the home. Dramatically lower patient burden and significantly faster recruitment.

Recruitment planning: Where are the patients?

Because of diagnostic delays (12–18 months) and strict eligibility windows, trials must recruit from the annual flow of new diagnoses, not standing prevalence.

Key Takeaway for Targeted Therapies: For rare targeted populations (such as SOD1, which represents ~2% of total ALS cases), the flow collapses to just a few dozen new cases per year per country. You cannot capture a patient flow that thin relying solely on top-tier national centres. Reaching patients directly at home is essential.

Key takeaways & conclusions

1. Route Drives Design: Oral therapies allow for heavy decentralisation (5 site visits vs 9 home), IV can move home after safety tolerance is established, and intrathecal studies benefit from local site delivery.
2. Assessments Belong at Home: Functional rating, breathing, strength, blood draws, and PROs can all be comfortably performed by a visiting nurse.
3. Keep Procedures Local: Lumbar punctures do not require a major national hospital hub—they can be performed at qualified regional facilities.
4. Target Rare Subpopulations Aggressively: The rarer the genetic target, the higher the need to take the trial to the patient rather than expecting them to travel.

Appendix 1: Illustrative Phase 3 Assessment Schedule

X = Assessment Performed (4-Week Cadence)

Appendix 2: Key Clinical Networks & Advocacy Groups

Clinical Networks & Registries:

• NEALS (Northeast ALS Consortium, USA)
• TRICALS & ENCALS (European Networks)
• MND Association Care Centre Network (UK)
• FILSLAN (France), MND-NET (Germany), PARALS (Italy), JaCALS (Japan)
• CDC National ALS Registry (USA) & Project MinE (Global)

Advocacy Organizations:

• The ALS Association, I AM ALS, ALS TDI (USA)
• MND Association & My Name’5 Doddie Foundation (UK)
• ARSLA (France), AISLA (Italy), ALS Canada, MND Australia