Amyotrophic Lateral Sclerosis (ALS)
Conditions
Keywords
Amyotrophic Lateral Sclerosis, ALS, monoclonal antibody, motor neuron disease, MND
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.
Interventions
BIOLOGICALVHB937
VHB937 solution for infusion
OTHERPlacebo
Solution for infusion
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Blinded placebo for infusion
Intervention model description
Double-blind, Randomized 2:1 ratio
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-CTROUGH | Screening to Week 12 | CTROUGH - Minimum observed concentration of VHB937 in CSF |
Countries
Australia, Belgium, Canada, China, Denmark, France, Germany, Ireland, Italy, Netherlands, Poland, South Korea, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed