A Study to Evaluate the Safety, Efficacy, and Pharmacodynamics of PLL001 in ALS Patients
NCT Number: NCT06513546
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Amyotrophic Lateral Sclerosis|ALS
Interventions: DRUG: PLL001 or placebo daily subcutaneous injections
Sponsor: PLL TX AUSTRALIA PTY LTD
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 153
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-10-15
Completion Date: 2026-12-15

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.

Primary Outcome Measures: 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 Outcome Measures: 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, 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), 24 weeks