A Phase II Study of ALT001 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Overview

Official title

A Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Dose-ranging Study to Evaluate the Efficacy and Safety of ALT001 in Patients With Amyotrophic Lateral Sclerosis

Brief title

A Phase II Study of ALT001 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Registration type

ClinicalTrials.gov

NCT number

NCT07833618

Status

Not yet recruiting

Study category

Interventional, Drug trial, Biomarker

Sponsor / center

Darwin Origin (Hubei) Biopharmaceutical Co., Ltd.

Research center

Not stated in the official study record.

Collaborators

Not stated in the official study record.

Study type

Interventional study

Phase

Phase 2

Enrollment

150

Start date

09-01-2026

Primary completion date

01-01-2028

Estimated / actual completion date

12-31-2028

Last source update

09-22-2026

What is being studied?

ALT001 is an allogeneic unrelated human umbilical cord mesenchymal stem cell-derived protein complex under investigation for the treatment of amyotrophic lateral sclerosis (ALS). This is a multicenter, randomized, double-blind, placebo-controlled, Phase 2 dose-ranging study in patients with ALS. Approximately 150 participants will be randomized 1:1:1 to receive ALT001 1.0 μg/kg, ALT001 2.0 μg/kg, or matching placebo by intravenous infusion during the 24-week double-blind (DB) treatment period. During the OLE period, the active treatment groups will continue to receive their original dose under blinded conditions, whereas the placebo group will undergo re-randomization in a 1:1 ratio to receive 1.0 or 2.0 μg/kg ALT001. The primary objective is to evaluate the dose-response relationship and efficacy of ALT001 at 1.0 and 2.0 μg/kg and to determine the recommended dose for subsequent studies. Secondary objectives include assessment of biomarkers related to efficacy and exploration of changes in cytokines, immune function, proteomics, and immunogenicity (anti-drug antibodies, ADA), as well as evaluation of the safety of ALT001.

Intervention(s)

Who may be eligible?

This is a simplified summary. The official study team or research center determines eligibility.

Population / disease status

Sporadic ALS, Diagnosed ALS

Diagnosis / conditions

Amyotrophic Lateral Sclerosis (ALS)

Age

18 Years to 75 Years

Disease duration

≤ 12 months

Respiratory criteria

The official eligibility criteria include language relevant to this topic; review the full criteria below.

ALSFRS-R criteria

The official eligibility criteria include language relevant to this topic; review the full criteria below.

Genetic criteria

Not stated in the official study record.

Medication requirements

The official eligibility criteria include language relevant to this topic; review the full criteria below.

Major inclusion and exclusion criteria from the official record

Inclusion Criteria:

1. Participants or their guardians must be able to understand the procedures and methods of this study, communicate adequately with the investigator, be willing to strictly comply with the clinical trial protocol to complete the study, and voluntarily sign a written informed consent form, or have informed consent signed by a legally authorized representative.
2. Age 18 to 75 years (inclusive of both boundaries), of either sex.
3. Diagnosis of definite or probable ALS according to the revised El Escorial criteria of the World Federation of Neurology for amyotrophic lateral sclerosis, including both familial and sporadic ALS patients.
4. Forced vital capacity (FVC) ≥ 50% of predicted at the screening visit.
5. Total ALSFRS-R score ≥ 30 and ≤ 40 prior to enrollment.
6. If receiving riluzole or edaravone treatment before enrollment, participants must have been on a stable dose for ≥ 30 days prior to Day 1 of this study, and must maintain that dose until the final study visit.

Exclusion Criteria:

1. Have other known diseases associated with motor neuron dysfunction that may confound or obscure the diagnosis of ALS.
2. History of alcohol dependence or drug abuse within 6 months prior to screening, judged by the investigator to be unsuitable for participation in this study.
3. Apparent cognitive impairment (MMSE scale: ≤19 for the illiterate group, ≤22 for the primary school group, and ≤26 for the junior high school and above group \[\>8 years of education\]), or other unstable psychiatric disorders that the investigator considers unsuitable for participation (including suicidal intent, untreated major depression, etc.).
4. Continuous use of non-invasive ventilation (NIV), diaphragm pacing system, or invasive ventilation (tracheostomy) at screening.
5. Severe autoimmune diseases, myeloproliferative disorders, leukemia or lymphoma, malignant tumors, fractures, or severe scoliosis at screening, which the investigator considers would affect study evaluation.
6. Other severe and/or uncontrolled major organ or unstable systemic diseases, including but not limited to uncontrolled diabetes, unstable angina, cerebrovascular accident or transient ischemic attack (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), severe congestive heart failure, uncontrolled hypertension, uncontrolled active infection, severe hepatic, renal or other severe metabolic diseases, or severe gastrointestinal diseases.
7. Positive hepatitis B surface antigen (HBsAg) with HBV-DNA \> upper limit of normal (if HBsAg is negative, HBV-DNA testing is not required); positive hepatitis C virus (HCV) antibody with HCV-RNA \> upper limit of normal (if anti-HCV is negative, HCV-RNA testing is not required); positive human immunodeficiency virus (HIV) antibody; or positive Treponema pallidum test.
8. Pregnant or lactating women, and those planning to conceive during the medication period or within 3 months after stopping the medication.
9. Participated in another interventional clinical study within 4 weeks prior to this study; received stem cell or exosome therapy within 1 year, or previously received ASO drug treatment or gene therapy.
10. Judged by the investigator to be unsuitable for participation in this study (e.g., significantly clinically significant abnormalities in physical examination or laboratory tests).

Genetics

Gene-specific study?

Yes

Gene or variant

Other specified ALS gene

Genetic test required?

Not stated in the official study record.

Known carrier required?

Not stated

Confirmed pathogenic variant required?

Not stated in the official study record.

Presymptomatic carriers eligible?

Not stated in the official study record.

At-risk relative eligible?

Not stated

Genetic test provided?

Not stated in the official study record.

Genetic counseling provided?

Not stated in the official study record.

Results returned / offered?

Not stated

Family history required?

Not stated in the official study record.

Study design

Randomized?

Not stated in the official study record.

Allocation

Not stated in the official study record.

Intervention model

Not stated in the official study record.

Masking

Not stated in the official study record.

Placebo

Yes

Primary purpose

Not stated in the official study record.

Endpoints

Primary outcome measures

• Change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score

Secondary outcome measures

• ALSFRS-R slope from baseline to Week 24 (double-blind period)
• ALSFRS-R slope from baseline to Week 48 (overall study period)
• ALSFRS-R slope from Week 25 to Week 48 (open-label extension period)
• Assessment of Combined Assessment of Function and Survival (CAFS)
• Assessment of ventilator-free survival (VAFS)
• Change from baseline in forced vital capacity (FVC) /slow vital capacity (SVC) percent predictedpercent predicted
• Concentration of cytokines in serum (IFN-γ, IL-10, IL-13, IL-1β, IL-2, IL-4, IL-5, IL-6, GRO-α, TNF-α, IL-2)
• Change from baseline in ALSAQ-40 total score
• Change from baseline in ROADS total score
• Change from baseline in modified Ashworth scale score
• Change from baseline in grip strength (kg)
• Change from baseline in muscle strength (MRC sum score)
• Change from baseline in ALS Functional Staging System stage
• Concentration of neurofilament light chain (NfL) in plasma
• Concentration of TAR DNA-binding protein 43 (TDP-43) in plasma
• Concentration of superoxide dismutase 1 (SOD1) in plasma
• Concentration of immunoglobulins in serum (IgG, IgM, IgA)
• Number and percentage of T-cell subsets in blood (CD3+CD4+, CD3+CD8+, CD28+, CD16+)
• Plasma proteomics profile
• Incidence of treatment-emergent anti-drug antibodies (ADA)
• Incidence of adverse events (AEs) and serious adverse events (SAEs)

A biomarker outcome should not automatically be interpreted as a clinical outcome.

Locations

Contact

Central contact: Pengfei Zhang, Director of Clinical Operations · zhangpengfei@darwincell.net · +86-13911241040