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Trial registered on ANZCTR


Registration number
ACTRN12622000927729
Ethics application status
Approved
Date submitted
27/06/2022
Date registered
29/06/2022
Date last updated
7/10/2023
Date data sharing statement initially provided
29/06/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
An open-label, phase 1b study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of a single dose of PMX205 in patients with amyotrophic lateral sclerosis
Scientific title
An open-label, phase 1b study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of two doses of PMX205 in patients with amyotrophic lateral sclerosis
Secondary ID [1] 307439 0
None
Universal Trial Number (UTN)
U1111-1279-8030
Trial acronym
Linked study record
This study is a follow up study to ACTRN12619001639112

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 326804 0
Motor Neuron Disease 326805 0
Parkinson's Disease 326806 0
Condition category
Condition code
Neurological 324022 324022 0 0
Neurodegenerative diseases
Inflammatory and Immune System 324023 324023 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention to be administered is PMX205, a non approved experimental therapy which inhibits the complement cascade.
The doses administered are 0.4 mg/kg and 0.8 mg/kg of PMX205 by a single injection and will be administered on one occasion only. The mode of administration is by subcutaneous injection to the upper abdomen and the drug will be administered by medical staff in the clinic.
Intervention code [1] 323882 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331812 0
To assess the safety and tolerability of a single dose of PMX205 administered by subcutaneous (SC) injection in patients with amyotrophic lateral sclerosis.
Safety will be assessed by changes in clinical parameters such as blood chemistry, ECG changes, respiratory changes using Common Terminology for Adverse Events (Version 5.0) and any injection site reactions using a common grading score for parameters such as redness and/or swelling.
Timepoint [1] 331812 0
1 hour, 8 hours and 24 hours post administration of PMX205
Secondary outcome [1] 411251 0
To determine the plasma pharmacokinetics (PK) of PMX205
Plasma: PMX205 concentrations and plasma PK parameters estimated using noncompartmental analysis (e.g. Cmax, Tmax, AUC0-last, AUC0-inf, Kel, t1/2).
Timepoint [1] 411251 0
o PK analysis at 0, 0.5, 1, 2, 4, 8 and 24 hours following dosing.
Secondary outcome [2] 411252 0
To evaluate PMX205 levels in the cerebrospinal fluid (CSF) after dosing at a single level
Timepoint [2] 411252 0
PMX205 levels will be measured at 1 and 24 hours post adminsistration.
Secondary outcome [3] 411253 0
To evaluate PMX205 pharmacodynamic (PD) activity by measuring inflammatory cytokine levels in whole blood following C5a challenge to peripheral immune cells
Timepoint [3] 411253 0
Cytokine levels will be measured at 0, 1, 2 and 24 hours post administration

Eligibility
Key inclusion criteria
1. Male or female volunteers 18-75 years of age.
2. Able and willing to provide written informed consent prior to the performance of any study-specific procedures.
3. Have possible, probable, probable laboratory-supported, definite, or definite familial laboratory-supported amyotrophic lateral sclerosis (ALS) in accordance with the El-Escorial criteria
4. Have familial or sporadic ALS.
5. Have slow vital capacity (SVC) of greater than or equal to 50% of predicted value for gender, height and age
6. If on riluzole, must be on a stable dose for at least 30 days
7. If on edaravone, must have completed 2 cycles and are expected to remain on the same dose throughout the study
8. Able to provide informed consent. If the patient is not able to provide written consent due to aggravation of disease condition, written informed consent may be provided by a legally authorized representative
9. Have venous access sufficient to allow for blood sampling
10. Have a coagulation profile within normal reference range for the population or study site, or results with acceptable deviations that are judged by the Principal Investigator (PI) to be not clinically significant.
11. Have adequate bone marrow reserve, renal function and liver function as defined below (and all other laboratory results within normal reference range or with acceptable deviations that are judged by the PI to be not clinically significant):
• Haemoglobin greater than or equal to 100 g/L
• Absolute neutrophil count greater than or equal to 1.5 × 109/L
• Platelet count greater than or equal to 100 × 109/L
• Estimated creatinine clearance greater than or equal to 60 mL/min (calculated using the Cockcroft-Gault formula)
• ALT, AST, and/or alkaline phosphatase less than or equal to 2 × ULN
• Total bilirubin less than or equal to 1.5 × ULN
• Serum albumin greater than or equal to 2.8 g/dL
12. BMI between 18.0 and 30.0 kg/m2, inclusive.
13. Non-smokers or ex-smokers who have ceased smoking greater than 6 months prior to the screening visit and have no more than one pack-year history of smoking.
14. Women who are not of child-bearing potential may be enrolled and are defined as women who:
• have been surgically sterilized; or
• are post-menopausal, as defined by amenorrhea for at least 12 consecutive months (and not induced by medical conditions such as anorexia nervosa and not taking medications that induced the amenorrhea, e.g., oral contraceptives, hormones, gonadotropin releasing hormones, anti-estrogens, selective estrogen receptor modulators, or chemotherapy) and confirmed by a serum follicle-stimulating hormone (FSH) level in the post-menopausal range.
15. Women of childbearing potential may be enrolled if they are not pregnant or lactating and agree to use both a barrier method of contraception (i.e. a condom or diaphragm) and a highly-effective method of contraception, from screening until 60 days after the last dose of study treatment. Highly-effective methods of contraception are associated with a pregnancy rate of less than 1% when used correctly and consistently, and include hormonal contraception and intrauterine devices. Abstinence from heterosexual intercourse is an acceptable alternative if this is the usual and preferred lifestyle of the subject.
16. Male subjects, if not surgically sterilized, must agree to use adequate contraception and not donate sperm from admission to the clinical research unit until 120 days after the last dose of study treatment. Adequate contraception is defined as a condom combined with female partner use of hormonal contraception or an intrauterine device. Abstinence from heterosexual intercourse is an acceptable alternative if this is the usual and preferred lifestyle of the subject.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Have a history or presence of medical illness including, but not limited to, any cognitive, cardiovascular, hepatic, haematological, renal, endocrine, or psychiatric, or any clinically significant laboratory abnormality that indicates a medical problem that would preclude study participation
2. Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV)-1 or HIV-2 antibody at screening.
3. Show evidence of hepatitis B virus (HBV) and/or positive hepatitis B surface antigen
4. Are women who are lactating.
5. Have undergone a tracheostomy unless it was removed at least 6 months prior
6. Are on feeding tube, unless the insertion of a feeding tube is considered prophylactic
7. Are on nasal intermittent positive pressure ventilation (NIPPV) > 4 hours per day or at the discretion of the medical monitor
8. Have undergone stem cell therapy
9. Have any other unbalanced progressive pathology
10. Have experienced weight loss > 10% of their weight before disease
11. Have been on drugs that may interfere with the process of neuroinflammation: drugs with anti-inflammatory properties within 30 days of screening, e.g., corticosteroids, azathioprine, anti-tumor necrosis factor (TNF), antibiotics. [NSAIDs are allowed, except from 48 hours before dosing until 24 hours following dosing.]
12. Previous treatment with PMX205 or other complement system inhibitor.
13. Presence of an active infection or body temperature > 37.5°C at screening or admission to the clinical trial unit.
14. Clinically significant history of chronic or recurrent infections, including opportunistic infections.
15. History of splenectomy.
16. Use of systemic immunosuppressive medications in the past 2 years.
17. Is taking anti-coagulant medication(s) and cannot stop the medication(s) for 2 weeks before lumbar puncture.
18. History of any medical or surgical condition where lumbar puncture is contraindicated.
19. Presence of a local skin infection or other dermatological condition in the lumbar region, which the PI considers would complicate a lumbar puncture.
20. Received an investigational therapy within 30 days (or 5 half-lives, whichever is longer) prior to PMX205 administration.
21. History of clinically-significant allergic reactions, including hypersensitivity to penicillins, cephalosporins and related antibiotics.
22. History of alcohol or drug abuse.
23. Positive screen for drugs of abuse (including opiates, cocaine, amphetamines, MDMA, cannabinoids, barbiturates and benzodiazepines) or alcohol at screening.
24. 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).
25. Donation or loss of more than 400 mL of blood within 60 days of trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Descriptive statistics for continuous measures will include number of observations (n), mean, standard deviation (SD), minimum, median and maximum. For categorical measures, descriptive statistics will include count and percent of treatment group for each value. Safety endpoints will not be inferentially analysed. Visit values and change from Baseline (Day 1), including the overall results across all eight subjects, will be reported for the safety, PK and PD parameters. For outcome measures without a scheduled Baseline assessment, change from the Admission Day (Day -1) will be used instead.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/08/2022
Actual
15/12/2022
Date of last participant enrolment
Anticipated
30/11/2022
Actual
22/08/2023
Date of last data collection
Anticipated
30/12/2022
Actual
22/09/2023
Sample size
Target
8
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 22622 0
The Wesley Hospital - Auchenflower
Recruitment postcode(s) [1] 37894 0
4066 - Auchenflower

Funding & Sponsors
Funding source category [1] 311709 0
Commercial sector/Industry
Name [1] 311709 0
Alsonex Pty Ltd
Country [1] 311709 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Alsonex Pty Ltd
Address
Level 23, 307 Queen St, Brisbane, 4000, Queensland
Country
Australia
Secondary sponsor category [1] 313167 0
None
Name [1] 313167 0
Address [1] 313167 0
Country [1] 313167 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311161 0
The UnitingCare Health Human Research Ethics Committee
Ethics committee address [1] 311161 0
Level 5, 192 Ann Street
Brisbane QLD 4000
Ethics committee country [1] 311161 0
Australia
Date submitted for ethics approval [1] 311161 0
28/06/2022
Approval date [1] 311161 0
29/11/2022
Ethics approval number [1] 311161 0
202210

Summary
Brief summary
The primary objective is to evaluate the safety and tolerability of a single dose of PMX205 in individuals with ALS. The secondary objectives are: to determine the plasma pharmacokinetics (PK) of PMX205, evaluate PMX205 levels in the cerebrospinal fluid (CSF) after dosing at a single level, and to evaluate PMX205 pharmacodynamic (PD) activity by measuring cytokine levels following C5a challenge in peripheral immune cells. It is important to determine the extent to which PMX205 crosses the blood-brain barrier and enters brain tissue in individuals with ALS.

PMX205 is to be administered as a subcutaneous (SC) injection into the anterior abdomen. Patients who have ALS or are likely to have ALS will be selected by the investigators based on history, examination, imaging and laboratory results. A total of up to 8 participants will be enrolled and assessed for safety (physical exam and clinical laboratory pathology), PMX205 PK and PMX205 PD during the study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120162 0
A/Prof Robert Henderson
Address 120162 0
Wesley Medical Research
Level 8 East Wing (The Wesley Hospital), 451 Coronation Dr, Auchenflower, QLD 4066
Country 120162 0
Australia
Phone 120162 0
+61 7 3193 3387
Fax 120162 0
+61 7 3319 6693
Email 120162 0
[email protected]
Contact person for public queries
Name 120163 0
Robert Henderson
Address 120163 0
Wesley Medical Research
Level 8 East Wing (The Wesley Hospital), 451 Coronation Dr, Auchenflower, QLD 4066
Country 120163 0
Australia
Phone 120163 0
+61 7 3193 3387
Fax 120163 0
+61 7 3319 6693
Email 120163 0
[email protected]
Contact person for scientific queries
Name 120164 0
Robert Henderson
Address 120164 0
Wesley Medical Research
Level 8 East Wing (The Wesley Hospital), 451 Coronation Dr, Auchenflower, QLD 4066
Country 120164 0
Australia
Phone 120164 0
+61 7 3193 3387
Fax 120164 0
+61 7 3319 6693
Email 120164 0
[email protected]

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 Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.