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

NCT ID: NCT06513546

Last Updated: 2025-07-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

153 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-08

Study Completion Date

2026-12-15

Brief Summary

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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.

Detailed Description

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Part 1 (Single Ascending Dose 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).

Conditions

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Amyotrophic Lateral Sclerosis ALS

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
double-blind study

Study Groups

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PLL001 dose 5x

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

Group Type EXPERIMENTAL

PLL001 or placebo daily subcutaneous injections

Intervention Type 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)

PLL001 dose 10x

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

Group Type EXPERIMENTAL

PLL001 or placebo daily subcutaneous injections

Intervention Type 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)

placebo

Saline daily subcutaneous injections

Group Type PLACEBO_COMPARATOR

PLL001 or placebo daily subcutaneous injections

Intervention Type 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)

Interventions

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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)

Intervention Type DRUG

Other Intervention Names

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Poly-L-lysine conjugates with acetate, butyrate, lactate, propionate

Eligibility Criteria

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Inclusion Criteria

1. Males and females ≥18 years of age at the time of informed consent.
2. 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.
3. Must have familial or sporadic ALS.
4. 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.
5. 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.
6. 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.
7. 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.
8. Seated slow vital capacity (SVC) ≥ 50% of predicted value for gender, height, and age at screening.
9. Must be willing and able to comply with the requirements of the protocol and must be available to complete the study.
10. Must provide written informed consent to participate in the study.

Exclusion Criteria

1. Has dementia or significant neurological, psychiatric, systemic, or organic disease, uncontrolled or that may interfere with the conduct of the trial or its results.
2. Pregnant or nursing females.
3. History of drug/chemical/substance/alcohol abuse within the past 2 years prior to Screening, including cannabinoid therapies.
4. 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).
5. Mechanical ventilation via tracheostomy or dependence on non-invasive ventilation, (\> 16 hours / day). (Lesser intermittent use of non-invasive ventilation eg, continuous positive airway pressure, non-invasive bi-level positive airway pressure or non-invasive volume ventilation is not an exclusion).
6. Patients positive for human immunodeficiency virus (HIV) antibody, hepatitis C antibody, or for hepatitis B virus surface antigen (HBsAg).
7. 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.
8. Experimental agent within 30 days or 5 half-lives, whichever is longer, prior to study drug administration (Part 1 only).
9. Any other condition which, in the opinion of the Investigator, precludes participation in the study.
10. Dependents of the Sponsor or Investigator.
11. Known allergy to the study drug and/or its constituents.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PLL TX AUSTRALIA PTY LTD

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tina Soulis

Role: STUDY_DIRECTOR

Alithialifesciences

Locations

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Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status RECRUITING

Neuroscience Research Australia

Sydney, New South Wlaes, Australia

Site Status RECRUITING

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Site Status RECRUITING

Wesley Research Institute

Brisbane, Queensland, Australia

Site Status RECRUITING

Gold Coast University Hospital

Southport, Queensland, Australia

Site Status RECRUITING

Flinders Medical Centre

Adelaide, South Australia, Australia

Site Status RECRUITING

Alfred Health

Melbourne, Victoria, Australia

Site Status RECRUITING

Calvary Health Care, Bethlehem

Melbourne, Victoria, Australia

Site Status RECRUITING

Monash Medical Centre, Neuroscience Research

Melbourne, Victoria, Australia

Site Status RECRUITING

The Perron Institute for Neurological and Translational Science

Perth, Western Australia, Australia

Site Status RECRUITING

Countries

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Australia

Central Contacts

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Tina Soulis

Role: CONTACT

+61 (0) 429 300 705

Facility Contacts

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Cecilia Cappelen-Smith, MD

Role: primary

+61 2 8738 3646

Kelsey Dobell-Brown, Stzudy Manager

Role: backup

+61 2 8738 7168

Matthew Kiernan, Professor, MD

Role: primary

Hannah Timmins, Clinical Research and Trials M

Role: backup

+ 61 (0) 2 9399 1016

Antony Winkel, MD

Role: primary

Helen Rodgers, Nurse Unit Manager

Role: backup

+ 61 (0) 752023059

Robert Henderson, MD

Role: primary

Po Sheng yang, MD

Role: backup

Arman Sabet, Professor, MD

Role: primary

Vincent Sapean, Clinical Research and Trials M

Role: backup

+61 (0)417 221 342

David Schulz, MD

Role: primary

+61 8 8204 4187

Karalyn Ernst, Study Coordinator

Role: backup

+61 8 8204 5712

Edrich Rodrigues, MD

Role: primary

Branko Borojevic, MD

Role: backup

Susan Mathers, MD, Professor

Role: primary

+ 61 (0) 3 9596 2853 page 277

Emma Windebank, Senior Research Coordinator

Role: backup

+ 61 (0) 3 9834 9430

Susan Mathers, MD, professo

Role: primary

+ 61 (0) 3 9596 2853 page 277

May Ho, Clinical Research Nurse

Role: backup

+ 61 (0) 3 9594 3051

Dev Nathani, MD

Role: primary

Ruby Shehatha, Research Nurse Lead

Role: backup

+61 8 6457 0200

Other Identifiers

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PLL001-101

Identifier Type: -

Identifier Source: org_study_id

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