A Clinical Trial to Learn About the Effects of VHB937 in People With Amyotrophic Lateral Sclerosis (ALS)

Phase 2

Recruiting

• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Interventions: Biological: VHB937; Other: Placebo

• Registration Number: NCT06643481
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group Phase II study to evaluate the efficacy and safety of VHB937 in participants with early-stage ALS (within 2 years of ALS symptoms onset). The study comprises a core double-blind (DB) 40-week treatment period followed by an open label extension (OLE).

Detailed Description

The main questions this trial aims to answer in comparing VHB937 to placebo are:

* How long will participants live without needing permanent help from a machine to breathe after starting the trial treatment?

* What is the change in the participant's ability to perform daily activities? This will be measured using a questionnaire called the amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R).

* What adverse events are reported during this trial? An adverse event is any sign or symptom that participants have during a trial. Adverse events may or may not be caused by treatments in the trial. The trial doctors will check participants' ALS and general health throughout the trial.

Study Timeline

• Study First Submitted: 2024-09-30
• Study First Submitted QC: 2024-10-12
• Study First Posted: 2024-10-16
• Study Start: 2024-10-17
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-16
• Primary Completion: 2027-01-29
• Study Completion: 2028-06-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 225

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.

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 hematological 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 Behavior" 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	VHB937	I.V. infusions
Arm 2	Placebo	I.V. infusions

Primary Outcome Measures

Name	Time	Method
The composite of PAV-free survival and change in ALSFRS-R. Analysis method: Combined Assessment of Function and Survival (CAFS)	Baseline to DB Week 40	To compare the efficacy of VHB937 vs. placebo on a composite of permanent assisted ventilation (PAV) free survival and function in DB epoch

Secondary Outcome Measures

Name	Time	Method
Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-CTROUGH	Screening to Week 12	CTROUGH - Minimum observed concentration of VHB937 in CSF
ALS Functional Rating Scale Revised (ALSFRS-R) total score	Baseline to DB Week 40 or until death or PAV (whichever occurs first) and Baseline to OLE Week 100 or until death or PAV (whichever occurs first	To assess the efficacy of VHB937 on functional decline in DB and OLE epochs.
Slow Vital Capacity (SVC) (% of predicted normal value)	Baseline to DB Week 40 or until death or PAV (whichever occurs first) and Baseline to OLE Week 100 or until death or PAV (whichever occurs first)	To assess the efficacy of VHB937 in delaying decline in respiratory function in DB and OLE epochs.
Ratio to baseline in Neurofilament Light (NfL) concentration in serum	DB up to Week 40; DB and OLE up to Week 100]	To assess the effect of VHB937 on a biomarker of neurodegeneration in DB and OLE epochs.
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline to end of study	To assess the safety and tolerability of VHB937 in DB and OLE epochs.
Time to death and Time to event (death or PAV, whichever comes first).	Baseline to DB Week 40	To assess the efficacy of VHB937 vs. placebo on survival endpoints in DB epoch.
Time to death and Time to event (death or PAV, whichever comes first) - endpoints referring to treatment policy estimand	Baseline to OLE Week 100, and Baseline to end of study	To assess the efficacy of early vs. delayed VHB937 administration on survival endpoints (DB VHB937 followed by OLE VHB937 vs. DB placebo followed by OLE VHB937)
Patient Global Impression of change in functional ability and ALS symptom severity (PGI-C)	DB up to Week 40; DB and OLE up to Week 100	To assess change in ALS condition in DB and OLE epochs.
Change in QoL from baseline as measured with Amyotrophic Lateral Sclerosis Assessment Questionnaire -5 (ALSAQ-5)	DB up to Week 40; DB and OLE up to Week 100	To assess Quality of Life (QoL) with VHB937 in DB and OLE epochs.
Change in Clinician Global Impression of change in functional ability and ALS symptom severity (CGI-C)	DB up to Week 40; DB and OLE up to Week 100	To assess change in ALS condition in DB and OLE epochs.
Change in QoL from baseline as measured with EuroQoL 5 Dimension 5 Level (EQ-5D-5L)	DB up to Week 40; DB and OLE up to Week 100	To assess Quality of Life (QoL) with VHB937 in DB and OLE epochs.
Change in QoL from baseline as measured with 12-item Short form health survey (SF-12)	DB up to Week 40; DB and OLE up to Week 100	To assess Quality of Life (QoL) with VHB937 in DB and OLE epochs.
Pharmacokinetics (PK) of VHB937-CMAX	Day 1 to end of study	CMAX - The maximum concentration of VHB937 in serum
Pharmacokinetics (PK) of VHB937-TMAX	Day 1 to end of study	TMAX - The time to reach the maximum concentration of VHB937 in serum
Pharmacokinetics (PK) of VHB937-CTROUGH	Day 1 to end of study	CTROUGH - Minimum observed concentration of VHB937 in serum
To assess immunogenicity (IG) of VHB937	Day 1 up to end of study	To assess immunogenicity of Anti-VHB937 antibodies in serum
Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-CMAX	Screening to Week 12	CMAX - The maximum concentration of VHB937 in CSF
Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-TMAX	Screening to Week 12	TMAX - The time to reach the maximum concentration of VHB937 in CSF

Trial Locations

Locations (1)

Nerve and Muscle Center of Texas; 🇺🇸 Houston, Texas, United States