A Study to Evaluate the Safety, Efficacy, and Pharmacodynamics of PLL001 in ALS Patients

NCT06513546 | Not Yet Recruiting Phase 1

• 1 other identifier: PLL001-101
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 10

Brief Summary

FIH, Phase 1/2, multi-centre, randomised, double-blind, placebo controlled study with an optional open-label dosing extension to assess the safety, tolerability, efficacy, and Pharmacodynamics (PD) of single or multiple (up to 48 weeks QD) subcutaneous (SC) doses of PLL001 compared to placebo in subjects diagnosed with ALS.

Conditions

Amyotrophic Lateral Sclerosis; ALS

Outcome Measures

Primary Outcomes (3)

• Part 1: safety

  AEs, change from Baseline in other safety parameters (metric values) Haemotology: Haemoglobin g/L; Haematocrit L/L; Red Blood Cells X10\^12/L; White Blood Cells X10\^9/L; Platelets X10\^9/L; Neutrophils X10\^9/L; Eosinophils X10\^9/L; Lymphocytes X10\^9/L; Monocytes X10\^9/L; Basophils X10\^9/L; Mean corpuscular volume fL Biochemistry: Sodium mmol/L; Potassium mmol/L; Phosphate mmol/L; Calcium mmol/L; Urea mmol/L; Uric Acid mmol/L; Creatinine umol/L; Glucose mmol/L; Protein g/L; Albumin g/L; Bilirubin umol/L; ALP U/L; AST U/L; ALT U/L; GGT U/L; LDH U/L Coagulation: Prothrombin time sec; APTT sec; International Normalised Ratio; Fibrinogen g/L Urinalysis: RBC x10\^6/L; WBC x10\^6/L

  7 days

• Part 2: efficacy of PLL001 compared to placebo after 8, 16, and 24 weeks of once daily (QD) treatment

  Change from Baseline in ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised) scores. Minimum score of 0 and a maximum score of 48. Higher scores indicate better functional status and retained abilities. Specifically, a score of 48 represents the best functional status, while a score of 0 indicates the worst functional status

  24 weeks

• Part 2: survival after 8, 16, and 24 weeks of QD treatment for PLL001 compared to placebo

  Survival

  24 weeks

Secondary Outcomes (2)

• Part 2: safety

  24 weeks

• Part 2: efficacy over 24 weeks

  24 weeks

Study Arms (3)

PLL001 dose 5x

EXPERIMENTAL

PLL001 lowest dose (Poly-l-Lysine conjugates with acetate, butirate, lactate, propionate) daily subcutaneous injections

Drug: PLL001 or placebo daily subcutaneous injections

PLL001 dose 10x

EXPERIMENTAL

PLL001 highest dose (Poly-l-Lysine conjugates with acetate, butirate, lactate, propionate) daily subcutaneous injections

Drug: PLL001 or placebo daily subcutaneous injections

placebo

PLACEBO COMPARATOR

Saline daily subcutaneous injections

Drug: PLL001 or placebo daily subcutaneous injections

Interventions

PLL001 or placebo daily subcutaneous injections DRUG

PLL001 consists of the combination of 4 drug substances (DS) each being a linear poly-lysine flexible backbone with an average length of 70 L-lysines linked with 10% of conjugated side chains all being small chain fatty acids (SCFAs) (acetate, butyrate, lactate and propionate). The remaining 90% of the lysine residues are present as bromide salt. PLL001 DP is presented as 20 mL vials containing 16 mL of a sterilised solution for SC injection with the following formula (5× concentration)

Also known as: Poly-L-lysine conjugates with acetate, butyrate, lactate, propionate

PLL001 dose 10x; PLL001 dose 5x; placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥18 years of age at the time of informed consent.
• Diagnosed within the previous 1 year with laboratory-supported probable, clinically probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria.
• Must have familial or sporadic ALS.
• First ALS symptoms occurred no more than two (2) years prior to screening visit ALS disease duration from diagnosis no longer than 12 months at the Screening visit.
• If treated with riluzole, edaravone or any other approved ALS medication, treated with a stable dose for at least 4 weeks prior to Day 1.
• If documented, patient with an ALSFRS-R score progression between onset of the disease and Screening of \> 0.3 per month, confirmed with an ALSFRS-R score progression of ≥ 1 point during a 12 week prior to randomisation.
• Has a score of at least 26 overall, including a score of at least 3 on item #3 and at least 2 on each of the 12 ALSFRS-R individual component items at Screening and at least 2 on each of the 12 ALSFRS-R individual component items at randomisation.
• Seated slow vital capacity (SVC) ≥ 50% of predicted value for gender, height, and age at screening.
• Must be willing and able to comply with the requirements of the protocol and must be available to complete the study.
• Must provide written informed consent to participate in the study.

You may not qualify if:

• Has dementia or significant neurological, psychiatric, systemic, or organic disease, uncontrolled or that may interfere with the conduct of the trial or its results.
• Pregnant or nursing females.
• History of drug/chemical/substance/alcohol abuse within the past 2 years prior to Screening, including cannabinoid therapies.
• Significant symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within the past 2 weeks prior to study medication administration (at the discretion of the Investigator).
• Patients positive for human immunodeficiency virus (HIV) antibody, hepatitis C antibody, or for hepatitis B virus surface antigen (HBsAg).
• Sexually active females of childbearing potential and male subjects who are not practicing at least one method of hormonal or mechanical birth control with their partner during the study and for 90 days after the last dose of the study medication. Males and females who are not heterosexually active or who practice true abstinence are exempt from contraceptive requirements.
• Experimental agent within 30 days or 5 half-lives, whichever is longer, prior to study drug administration (Part 1 only).
• Any other condition which, in the opinion of the Investigator, precludes participation in the study.
• Dependents of the Sponsor or Investigator.
• Known allergy to the study drug and/or its constituents.

Sponsors & Collaborators

• PLL TX AUSTRALIA PTY LTD: lead

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Acetates; Butyrates; Lactic Acid; Propionates

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Lactates; Hydroxy Acids

Study Officials

• Tina Soulis

  Alithia Lifesciences

  STUDY DIRECTOR

Central Study Contacts

Tina Soulis

CONTACT

+61 (0)429 300 705; Tina.Soulis@alithialifesciences.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2024
• First Posted: July 22, 2024
• Study Start: April 8, 2026
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): June 15, 2027
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (10)