A clinical trial to learn about the effects of VHB937 in people with amyotrophic lateral sclerosis (ALS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

28 Feb 2025 → ongoing

Decision date (initial)

2025-01-16

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To compare the efficacy of VHB937 vs. placebo on a composite of permanent assisted ventilation (PAV) free survival and function in DB epoch

Secondary objectives 9

1. To assess the efficacy of VHB937 on functional decline in DB and OLE epochs.
2. To assess the efficacy of VHB937 in delaying decline in respiratory function in DB and OLE epochs.
3. To assess the effect of VHB937 on a biomarker of neurodegeneration in DB and OLE epochs.
4. To assess the safety and tolerability of VHB937 in DB and OLE epochs.
5. To assess the efficacy of VHB937 vs. placebo on survival endpoints in DB epoch.
6. 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)
7. To assess change in ALS condition in DB and OLE epochs.
8. To assess Quality of Life (QoL) with VHB937 in DB and OLE epochs.
9. To assess the pharmacokinetics (PK) and immunogenicity (IG) of VHB937 in DB and OLE epochs.

Conditions and MedDRA coding

Amyotrophic Lateral Sclerosis (ALS)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Signed informed consent must be obtained prior to participation in the study.
2. Sporadic or familial ALS diagnosed using the revised El Escorial criteria as clinically possible, probable, lab-supported probable, or definite ALS.
3. Age 18 years or older (19 years of age for S. Korea population according to the local adult age standard).
4. Onset of ALS symptoms within 24 months.
5. Slow Vital Capacity (SVC) greater or equal to 60% of predicted capacity for age, height, and sex.
6. ALSFRS-R total score greater or equal to 30
7. Treated or untreated with SoC therapy for ALS. If treated, must be on a stable dose of riluzole, for ≥ 30 days and/or edaravone oral or i.v. having completed at least one on-drug cycle prior to randomization.
8. Able and willing to travel to the site with or without assistance from their support network.

Exclusion criteria 10

1. 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.
2. 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.
3. History or current diagnosis of cardiac conditions or ECG abnormalities indicating significant risk of safety for participants in the study.
4. Clinical evidence of liver or renal disease/injury.
5. Laboratory evidence of hematological abnormalities
6. Active moderate or severe 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.
7. 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.
8. Presence of cancer, HIV, uncontrolled diabetes
9. History of active severe respiratory disease.
10. Taking any prohibited medications as listed on Table 6-4 of the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The composite of PAV-free survival and change in ALSFRS-R. Analysis method: Combined Assessment of Function and Survival (CAFS) [Time Frame: Baseline to DB Week 40]

Secondary endpoints 9

1. ALSFRS-R total score [Time Frame: Baseline to DB Week 40 or until death or PAV (whichever occurs first); Baseline to OLE Week 100 or until death or PAV (whichever occurs first)]
2. Slow Vital Capacity (SVC) (% of predicted normal value) [Time Frame: Baseline to DB Week 40 or until death or PAV (whichever occurs first); Baseline to OLE Week 100 or until death or PAV (whichever occurs first)]
3. Ratio to baseline in Neurofilament Light (NfL) concentration in serum [Timeframe: DB up to Week 40; DB and OLE up to Week 100]
4. Safety and tolerability parameters including adverse events, laboratory data, vital signs, electrocardiogram (ECG), Columbia Suicide Severity Rating Scale (C-SSRS) [Time Frame: Baseline to DB Week 40, Baseline to OLE Week 100, and Baseline to last scheduled visit or end of study]
5. Time to death and Time to event (death or PAV, whichever comes first). [Timeframe: Baseline to DB Week 40]
6. Time to death and Time to event (death or PAV, whichever comes first) – endpoints referring to treatment policy estimand [Time Frame: Baseline to OLE Week 100, and Baseline to end of study]
7. Clinician and Patient Global Impression of change in functional ability and ALS symptom severity (CGI-C and PGI-C) [Time Frame: DB up to Week 40; DB and OLE up to Week 100]
8. Change in QoL from baseline as measured with Amyotrophic Lateral Sclerosis Assessment Questionnaire -5 (ALSAQ-5), EuroQoL 5 Dimension 5 Level (EQ-5D-5L), 12-item Short form health survey (SF-12) [Time Frame: DB up to Week 40; DB and OLE up to Week 100]
9. PK in serum and CSF and Anti-VHB937 antibodies (ADAs) in serum [Time Frame for serum: DB up to Week 40, DB and OLE up to Week 100; DB and OLE up to last scheduled visit; For CSF: DB Week 12]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 11

Locations

11 EU/EEA countries · 43 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 132 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications