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Trial registered on ANZCTR


Registration number
ACTRN12619001639112
Ethics application status
Approved
Date submitted
8/11/2019
Date registered
25/11/2019
Date last updated
22/04/2020
Date data sharing statement initially provided
25/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised, double-blind, placebo-controlled, phase 1 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of PMX205 in healthy volunteers.
Scientific title
A randomised, double-blind, placebo-controlled, phase 1 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of PMX205 in healthy volunteers.
Secondary ID [1] 299759 0
PMX-205-001
Universal Trial Number (UTN)
U1111-1243-2230
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Motor Neuron Disease 315121 0
Parkinson's Disease 315122 0
Condition category
Condition code
Inflammatory and Immune System 313439 313439 0 0
Other inflammatory or immune system disorders
Neurological 313440 313440 0 0
Neurodegenerative diseases
Neurological 313583 313583 0 0
Parkinson's disease
Neurological 313584 313584 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part 1 (Single Ascending Dose)
The study will evaluate 5 Single Ascending Dose levels of PMX205 in 6 healthy subjects per dose level (4 receiving PMX205 and 2 receiving placebo). After screening and immunisation against meningococcal disease (ACWY and B serotypes), eligible subjects will be admitted to the clinical trial unit on day -1 and, following randomisation, will receive a single dose of PMX205 (0.02 mg/kg) or placebo by subcutaneous injection on day 1. The maximum dose to be administered will be 0.4 mg/kg. Subjects will be monitored for safety, pharmacokinetic and pharmacodynamic endpoints.
Escalation from one dose level to the next will only occur after review by the Safety Monitoring Committee of all safety data out to day 8. All dose levels will commence with 2 sentinel subjects (1 active and 1 placebo). Dosing of the remainder of the cohort (3 active and 1 placebo) will then proceed after a minimum of 48 hours, assuming there are no safety concerns in the sentinel group.
Part 2 (Multiple Ascending Dose)
Participants in Part 2 will not have participated in Part 1. The study will evaluate 3 dose levels of PMX205 in 8 healthy subjects per dose level (6 receiving PMX205 and 2 receiving placebo). the doses selected for Part 2 will be dependent on the outcome of Part 1. After screening and immunisation against meningococcal disease (ACWY and B serotypes), eligible subjects will be admitted to the clinical trial unit on day -1 and, following randomisation, will receive a single dose of PMX205 or placebo by subcutaneous injection on day 1. Subjects will be monitored for safety, PK and PD endpoints. Subjects will receive a single dose of PMX205 or placebo by SC injection on days 2, 3, 4 and 5.
Intervention code [1] 316016 0
Treatment: Drugs
Comparator / control treatment
Placebo controlled. The placebo is 5% dextrose solution.
Control group
Placebo

Outcomes
Primary outcome [1] 321915 0
Safety outcome measures: Adverse events (evaluated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), vital signs, physical examinations, 12-lead ECGs and clinical laboratory tests.
Timepoint [1] 321915 0
Baseline, 24 hours (primary timepoint) and thereafter on Days 2 and 3 with additional follow up on Day 8, and further follow up on Days 15 and 29 from the commencement of treatment.
Vital signs on day 1 performed within 30 mins (± 3 mins) prior to dosing; then at 30 and 60 (± 3 mins); and 2, 4, and 8 hours (± 10 mins) after dosing.
Secondary outcome [1] 376700 0
To determine the plasma pharmacokinetics (PK) of PMX205. The pharmacokinetic assessments include: Plasma PMX205 concentrations and plasma pharmacokinetic parameters estimated using noncompartmental analysis (e.g., Cmax, Tmax, AUC0-last, AUC0-inf, t1/2).
Timepoint [1] 376700 0
For Part 1: Plasma for pharmacokinetic analysis to be sampled within 30 mins (± 3 mins) prior to dosing; and then at 15, 30, and 60 mins (± 3 mins); 2, 4, 8, 12 and 24 hours (± 10 mins); and 48 hours (± 20 mins) after dosing.
For Part 2: Plasma for pharmacokinetic analysis to be sampled within 30 mins (± 3 mins) prior to dosing; and then at 15, 30, and 60 mins (± 3 mins); 2, 4, 8, 12 and 24 hours (± 10 mins) on Day 1 and day 5.
Secondary outcome [2] 376701 0
To evaluate PMX205 pharmacodynamic (PD) activity by measuring receptor occupancy on peripheral blood mononuclear cells (PBMC)
Timepoint [2] 376701 0
For Part 1: Blood for PBMC analysis to be sampled within 30 mins (± 3 mins) prior to dosing; and then at 1, 8 and 24 hours (± 10 mins).
For Part 2: Blood for PBMC analysis to be sampled within 30 mins (± 3 mins) prior to dosing; and then at 1, 8 and 24 hours (± 10 mins) after dosing on days 1, 3 and 5.

Eligibility
Key inclusion criteria
1. Male volunteers 18-55 years of age.
2. Able and willing to provide written informed consent prior to the performance of any study-specific procedures.
3. BMI between 18 and 32 kg/m2, inclusive.
4. Healthy as determined by medical history, physical examination, vital signs and 12-lead ECG at screening and day -1.
5. All clinical laboratory tests of blood and urine must be within the normal range or show no clinically relevant deviations as judged by the Investigator.
6. Non-smokers, ex-smokers (who have ceased smoking > 6 months prior to the screening visit and have no more than one pack-year history of smoking), or social smokers (no more than 5 cigarettes or equivalent per week and willing to refrain from smoking and using tobacco or nicotine products during the confinement periods).
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, metabolic, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine or other disease that, in the opinion of the Investigator, would impact on the study or the safety of the subjects..
2. Plasma creatinine, Plasma bilirubin, and ALT or AST > upper limit of normal (ULN), which is determined by the Investigator to be clinically significant. An exception is subjects with Gilbert’s syndrome, who are excluded if plasma bilirubin is > 1.5 × ULN.
3. Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV)-1 or HIV-2 antibody at screening.
4. Normal ECG findings or normal variants as determined by the Investigator, with QTc range less than or equal to 450 ms (Fridericia’s correction) at Screening and Day 1.
5. A family history of congenital long QT syndrome or unexplained sudden cardiac death.
6. History of malignancy, except for curatively treated basal cell carcinoma, squamous cell skin cancer or in-situ cervical carcinoma.
7. Use of prescription medications within 14 days prior to study drug administration.
8. Use of over-the-counter medication, vitamins or other food supplements, or herbal medications within 7 days prior to study drug administration. Exceptions are analgesics for minor ailments (e.g., paracetamol and/or ibuprofen up to 2 gm/day and 1.2 gm/day, respectively) and vitamins at standard replacement doses.
9. Intake of grapefruit (including its juice) from 48 hours prior to admission to the clinical research unit.
10. Previous treatment with PMX205 or other complement system inhibitor, including drugs such as Eculizumab.
11. Presence of an elevated body temperature or other possible sign of an active/acute infection at screening or admission to the clinical trial unit, which is determined by the Investigator to be clinically significant.
12. Clinically significant history of chronic or recurrent infections, including opportunistic infections.
13. History of splenectomy.
14. Use of systemic immunosuppressive medications in the past 2 years.
15. Received an investigational therapy within 30 days (or 5 half-lives, whichever is longer) prior to PMX205 administration.
16. History of clinically-significantclinically significant allergic reactions or anaphylaxis, including or any hypersensitivity to penicillins, cephalosporins and related antibiotics.
17. History of alcohol or drug abuse.
18. Positive screen for drugs of abuse (including amphetamines, methamphetamines, methadone, barbiturates, benzodiazepines, cocaine, opiates, methylenedioxymethamphetamine, phencyclidine, tetrahydrocannabinolopiates, cocaine, amphetamines, MDMA, cannabinoids, barbiturates and benzodiazepines) or alcohol at screening and day -1. At the Investigator’s discretion, the drug screen test may be repeated in the possible instance of a false positive due to e.g., poppy seed consumption.
19. Average intake of more than 14 units of alcohol per week (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits).
20. Donation or loss of more than 400 mL of blood within 60 days prior to study drug administration.
21. Undergone major surgery in the 6 months prior to screening.
22. Any condition which could confound the results of the study, interfere with participation in the study or increase the risks of study participation, in the opinion of the Investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table from a statistic book
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
The study plans to enrol a maximum of 54 healthy volunteers (30 in the SAD phase and 24 in the MAD phase of this study). The sample size was not based on statistical calculations but is considered adequate for the goals of this study.
Analysis populations
The following analysis populations are planned:
• Safety Population: All enrolled subjects who received at least one administration of study drug
• PK population: All subjects with at least one observation of a measurable level of PMX205.
• PD population: All subjects with at least one observation of a measurable level of C5aR1 receptor occupancy on PBMC.
Subjects will be analysed according to treatment received in all analysis populations.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 15128 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 28423 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 304226 0
Commercial sector/Industry
Name [1] 304226 0
Alsonex Pty Ltd
Address [1] 304226 0
Level 21, 71 Eagle Street
Brisbane, Queensland, 4000
Country [1] 304226 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Alsonex Pty Ltd
Address
Level 21, 71 Eagle Street
Brisbane, Queensland, 4000
Country
Australia
Secondary sponsor category [1] 304464 0
None
Name [1] 304464 0
Address [1] 304464 0
Country [1] 304464 0
Other collaborator category [1] 281024 0
Commercial sector/Industry
Name [1] 281024 0
GreenLight Clinical Pty Ltd
Address [1] 281024 0
Level 2, Suite 201, 134 William Street, Woolloomooloo, NSW 2011
Country [1] 281024 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304687 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 304687 0
55 Commercial Rd, Melbourne, VIC, 3004
Ethics committee country [1] 304687 0
Australia
Date submitted for ethics approval [1] 304687 0
30/01/2020
Approval date [1] 304687 0
11/02/2020
Ethics approval number [1] 304687 0
700/19

Summary
Brief summary
Motor neurone disease involves the destruction of the nerve cells that control your body’s movements. It is a progressive disease involving cells from the immune system attacking the nerve cells in the brain and spinal cord, which eventually causes death. The research project is testing the safety of a new drug called PMX205, which has been designed to interfere with how the body’s immune system attacks the brain. The purpose of this research is to determine if PMX205 is safe, if it affects the body as expected, and how much is in the blood after dosing. PMX205 will be injected under the skin in the top part of the abdomen.
Alsonex Pty Ltd has shown that PMX205 can slow down the disease in animals and is safe to use.
Medications, drugs and devices must be approved for use by the Australian Federal Government; the Therapeutic Goods Administration (TGA). PMX205 has not been approved for marketing by the TGA in Australia and is not yet approved anywhere else in the world. Therefore, the use of PMX205 in this study is experimental.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97866 0
Dr Ingrid Hopper
Address 97866 0
The Alfred Hospital
55 Commercial Rd, Melbourne VIC 3004
Country 97866 0
Australia
Phone 97866 0
+61390762000
Fax 97866 0
Email 97866 0
i.hopper@nucleusnetwork.com.au
Contact person for public queries
Name 97867 0
Dr Ingrid Hopper
Address 97867 0
The Alfred Hospital
55 Commercial Rd, Melbourne VIC 3004
Country 97867 0
Australia
Phone 97867 0
+61390762000
Fax 97867 0
Email 97867 0
i.hopper@nucleusnetwork.com.au
Contact person for scientific queries
Name 97868 0
Dr Alan D Robertson
Address 97868 0
Alsonex Pty Ltd
Level 21, 71 Eagle Street
Brisbane, Queensland, 4000
Country 97868 0
Australia
Phone 97868 0
+61417115582
Fax 97868 0
Email 97868 0
alan.robertson@alsonex.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy
What supporting documents are/will be available?
No other documents available
Summary results
No Results