ASTRALS

A Phase 2, Randomized, Double-blind, Placebo-controlled Parallel Group Study of VHB937 in Amyotrophic Lateral Sclerosis (ALS) Over 40 Weeks Followed by an Open Label Extension (ASTRALS)

UK Chief Investigator

Professor Chris McDermott

Research summary

The purpose of this trial is to learn about the effects of VHB937 compared with placebo in people with amyotrophic lateral sclerosis (ALS) previously treated with or without an ALS-approved therapy. Amyotrophic lateral sclerosis (ALS) is a nervous system disease that affects the cells in the brain and spinal cord that control muscle movement. This may lead to symptoms like muscle twitching, weakness in an arm or leg, and trouble swallowing. VHB937 is an antibody that works by activating a protein which directs important brain cells, called microglia, to protect nerve cells. This may prevent damage to the nerve cells and could help in the treatment of ALS. This trial has 2 parts: a core part and an open-label extension part. The core part is double-blinded and it contains a screening period and a 40-week treatment part where participants will receive either VHB937 or placebo. Since the core part is double-blind, neither participants nor the study doctor will know which treatment (i.e., VHB937 or placebo) they are assigned to, except in an emergency. Upon completion of the core part, participants who are eligible and willing to continue in the study will receive VHB937 during the open-label extension and will be assessed for long-term safety and efficacy. This open-label extension continues until the last participant stops the VHB937 treatment. About 225 participants are expected to join this trial from 19 countries worldwide. The pharmaceutical company sponsoring this study is Novartis AG Pharma.

This trial is randomised, double-blind (placebo-controlled) study. It is important to understand what this means. Click the links to go to the glossary of terms and read further explanations.

When considering taking part in any clinical trial, it is important to consider:

What the chances are of you being randomly assigned to either an intervention group or a placebo group
How long you would remain on this treatment allocation
If the study offers an open-label extension on completion of the main study.

For this study:

Randomisation is 2:1 ratio, which means that for every 2 participants randomised to receive the study drug, one participant will be randomised to receive placebo
Participants will remain on their treatment allocation for 40 weeks
The study has an open-label extension, which means that participants who complete the main part of the study, and who are eligible and willing to continue in the study, will receive the study drug during the open-label extension. The open-label extension is planned to continue up to the time when the study drug becomes available as a licensed treatment, or the study is cancelled.

Current status

Open to recruitment

Recruitment target

12 participants in the UK; up to 225 participants globally

Recruitment groups

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

Locations

Brighton, Principal Investigator: Andrew Barritt. Site opening to recruitment soon
London - St George's Hospital, Principal Investigator: Pablo Garcia Reitboeck. Site open for recruitment out-of-area
London - King's College Hospital, Principal Investigator: Ammar Al-Chalabi. Site opening to recruitment soon
London - University College London Hospital, Principal Investigator: Andrea Malaspina. Site opening to recruitment soon
Sheffield, Principal Investigator: Chris McDermott. Site opening to recruitment soon
Stoke, Principal Investigator: Tom Lambert. Site opening to recruitment soon

Information about study sites

Contact details

Email: novartis.email@novartis.com

Key dates

Recruitment opening date: 19 June 2025

Planned recruitment end date:

Inclusion / exclusion criteria

Key inclusion criteria:

are 18 years of age or older
male or female, if of childbearing potential, strict contraception required
have ALS confirmed by the trial doctors using different tests.
have mild symptoms of ALS as measured by the ALSFRS-R questionnaire (total score >=30).
have had symptoms of ALS (weakness) within 24 months of taking part in this trial.
have not received treatment for ALS or are currently on a stable dose of an approved treatment for ALS.
have the ability to slowly exhale a volume of air at least 60% of what is expected for the participant's sex, height and age.

Key exclusion criteria:

Use of other investigational drugs within 5 half-lives of screening, or within 30 days (e.g., small molecules) / or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 24 weeks after stopping study medication
History or current diagnosis of cardiac conditions or ECG abnormalities indicating significant risk of safety for participants in the study
Clinical evidence of liver or renal disease/injury
Laboratory evidence of haematological abnormalities
Presence of unstable psychiatric disease, cognitive impairment, neurological disease other than ALS, dementia or substance abuse that would impair ability of the participant to provide informed consent, in the investigator's opinion
Participants that reported 'yes' on any suicidal ideation section except for the "Non-Suicidal Self-Injurious Behaviour" in the past 2 years as per C-SSRS
Presence of cancer, HIV, Hep B, Hep C, tuberculosis, uncontrolled diabetes
History of active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis
Taking any prohibited medications

Funder

Novartis Pharmaceuticals

Sponsor

Novartis Pharmaceuticals

Study design

Interventional, randomised controlled trial

Intervention

Drug:
Placebo

Double-blind, Randomised 2:1 ratio

Phase

Outcome measures

Primary outcome measure

The composite of permanent assisted ventilation (PAV)-free survival and change in ALSFRS-R. Analysis method: Combined Assessment of Function and Survival (CAFS)

Secondary outcome measures

ALSFRS-R total score from baseline up to DB Week 40 or until death or PAV (whichever occurs first); and baseline up to OLE Week 100 or until death or PAV (whichever occurs first)
SVC (% of predicted normal value) from baseline up to DB Week 40 or until death or PAV (whichever occurs first); and Baseline up to OLE Week 100 or until death or PAV (whichever occurs first)
Ratio to baseline in NfL concentration in serum up to DB Week 40; and up to OLE Week 100
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) from baseline to end of study
Time to death and time to event (death or PAV, whichever comes first) up to DB Week 40; and up to OLE Week 100
Time to death and Time to event (death or PAV, whichever comes first) - endpoints referring to treatment policy estimand from baseline to OLE Week 100; and baseline to end of study
Clinician and Patient Global Impression of change in functional ability and ALS symptom severity (CGI-C and PGI-C) up to DB Week 40; and up to OLE Week 100
Change in QoL from baseline as measured with ALSAQ-5, EQ-5D-5L and SF-12 up to DB Week 40; and up to OLE Week 100
Pharmacokinetics (PK) of VHB937 Day 1 to end of study
To assess immunogenicity (IG) of VHB937 Day 1 to end of study

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