A Phase 1/2 interventional study of PLL001 or placebo daily subcutaneous injections in Amyotrophic Lateral Sclerosis and ALS, sponsored by PLL TX AUSTRALIA PTY LTD. Not yet recruiting. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-03-19.
Sponsored by PLL TX AUSTRALIA PTY LTD · Phase 1/2, Interventional, and Treatment
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.
Part 1 (Single Ascending Dose, competed) A total of 12 subjects will be randomised to 1 of 3 dose level cohorts (4 subjects per cohort). In each cohort, subjects will be randomised at a ratio of 3:1 to receive a single SC dose of PLL001 or placebo in a double-blind manner. The safety data of placebo subjects will be pooled.
Subjects will be admitted to the unit on the day prior to dosing (Day -1) and will be administered in a double-blind manner PLL001 or placebo via SC injection in the morning on Day 1. Subjects will remain hospitalised for a minimum of 24 hours for safety evaluation and will be discharged in the morning on Day 2. Safety data will be collected daily up to Day 7 (End of Study [EOS]).
Subjects that have completed Part 1 of the study will be eligible for screening in Part 2.
Part 2 (Multiple Dose Expansion)
Up to 141 subjects will be randomised to 1 of 3 treatments groups (2 dose level groups of PLL001 and 1 group of placebo) at a ratio of 1:1:1 (40 subjects per treatment group plus 21 patients for drop-out replacements).
The first 21 subjects (ie, 7 subjects per treatment group) will be dosed initially and will be randomised to 1 of the 3 treatment groups at a ratio of 1:1:1. These first 21 subjects will be monitored for the first 14 days of QD dosing. Following review of the safety data by the SRC and in the absence of any clinically significant safety signals, the remaining subjects will be enrolled.
Patients under riluzole will be allowed to continue their riluzole treatment and will be stratified at randomisation in Part 2 to ensure comparable numbers between each treatment group. Patients will also be stratified at randomisation in Part 2 based on TRICALS' risk profile calculator score (https://tricals.shinyapps.io/risk-profile/) to ensure comparable patients' ALS profiles between each treatment group.
Subjects will self-administer or have carers administer PLL001 or placebo daily (QD) via 2 × SC injections of 1 mL in a double-blind manner.
Addmionsitrationbs will be on-site on the morning of Day 1 and will self-administer or have carers administer on all other dosing days stopping the day before the visit on Day 169 (±5 days). Subjects will be discharged after a 4-hour observation period post-administration on Day 1.
Efficacy, safety, and compliance data will be collected during site visits which will occur every 8 weeks on Day 57, 113 and 169 (±5 days) (plus on Day 15 for all treated subjects).
Safety and compliance data will be collected via tele contact weekly (±3 days) on the weeks subjects do not attend a site visit.
Part 3 (Open-label Extension)
Subjects that consent to with the optional open-label treatment will commence open-label treatment at the visit on Day 169 (±5 days) and continue daily self dosing (or carer-administered dosing) of PLL001 10× via 2 × SC injections of 1 mL for an additional 24 weeks (for a total of 48 weeks of treatment) stopping the day before the visit on Day 337 (±5 days).
981 studies on the registry are indexed under Amyotrophic Lateral Sclerosis; 283 are open to participants now.
This study's planned enrollment of 153 is above the median of 36 across 667 interventional studies indexed under Amyotrophic Lateral Sclerosis.
Browse Amyotrophic Lateral Sclerosis studies →This is the only study on the registry with PLL TX AUSTRALIA PTY LTD as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
PLL001 lowest dose (Poly-l-Lysine conjugates with acetate, butirate, lactate, propionate) daily subcutaneous injections
Drug: PLL001 or placebo daily subcutaneous injections
PLL001 highest dose (Poly-l-Lysine conjugates with acetate, butirate, lactate, propionate) daily subcutaneous injections
Drug: PLL001 or placebo daily subcutaneous injections
Saline daily subcutaneous injections
Drug: PLL001 or placebo daily subcutaneous injections
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
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
Time frame: 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
Time frame: 24 weeks
Part 2: survival after 8, 16, and 24 weeks of QD treatment for PLL001 compared to placebo
Survival
Time frame: 24 weeks
Part 2: 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
Time frame: 24 weeks
Part 2: efficacy over 24 weeks
Progression-free survival (PFS) * Quality of life based on ALSAQ-40 score (Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 questions) * Respiratory function regression on Slow Vital Capacity score (SVC)
Time frame: 24 weeks
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Plan to share: No
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Amyotrophic Lateral Sclerosis→