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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03474263




Registration number
NCT03474263
Ethics application status
Date submitted
9/03/2018
Date registered
22/03/2018

Titles & IDs
Public title
IC14 for Rapidly Progressive Amyotrophic Lateral Sclerosis (ALS)
Scientific title
A Phase 2a, Open-Label Biomarker Study of IC14 for the Treatment of Patients With
Secondary ID [1] 0 0
ALS02
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Biologic: IC14 (monoclonal antibody against human CD14)

Experimental: IC14 (monoclonal anti-CD14 antibody) - Biologic: IC14 (monoclonal anti-CD14 antibody) 4 mg/kg intravenously followed by IC14 2 mg/kg intravenously on Days 2-4. This four-day cycle will be repeated on Days 8-11.


Treatment: Other: Biologic: IC14 (monoclonal antibody against human CD14)
IC14 intravenous infusion daily for four days on two successive weeks then MR-PET Scan evaluation for impact on glial activation.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Glial Activation
Timepoint [1] 0 0
one month
Primary outcome [2] 0 0
Serum neurofilament
Timepoint [2] 0 0
one month
Primary outcome [3] 0 0
Urinary p75 neurotrophin receptor
Timepoint [3] 0 0
one month
Secondary outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events (Safety, Tolerability)
Timepoint [1] 0 0
six weeks
Secondary outcome [2] 0 0
Immunogenicity
Timepoint [2] 0 0
six weeks
Secondary outcome [3] 0 0
Peak Plasma Concentration of IC14
Timepoint [3] 0 0
one month
Secondary outcome [4] 0 0
Pharmacodynamics
Timepoint [4] 0 0
one month

Eligibility
Key inclusion criteria
1. Capable of providing informed consent and informed consent form signed prior to initiation of any study-specific procedures.
2. Familial or sporadic ALS defined as clinically possible, probable, or definite by El Escorial Criteria.
3. Rapidly progressive ALS defined by the Revised ALS Functional Rating Scale (ALSFRS-R) slope =1 (48 minus ALSFRS-R score at screening / disease duration in months = 1).
4. Upper Motor Neuron Burden Score of = 25 (out of 45) at screening
5. First symptoms of ALS within 3 years of the screening visit
6. Age between 18 and 80 years at the time of the screening visit.
7. Not taking riluzole or edaravone or on a stable dose of riluzole or edaravone for at least 3 months prior to screening visit.
8. Adequate bone marrow reserve, renal and liver function:

1. absolute neutrophil count = 1500/µL
2. lymphocyte count < 6000/µL
3. platelet count = 150,000/µL
4. hemoglobin = 11 g/dL
5. creatinine clearance = 60 mL/min
6. alanine transaminase (ALT) and/or aspartate transaminase (AST) = 3x upper limits of normal (ULN)
7. total bilirubin = 1.5x ULN
8. serum albumin = 2.8 g/dL
9. Females of childbearing potential should be using and committed to continue using one of the following acceptable birth control methods:

1. Sexual abstinence (inactivity) for 1 month prior to screening through study completion; or
2. Intrauterine device (IUD) in place for at least 3 months prior to study through study completion; or
3. Stable hormonal contraception for at least 3 months prior to study through study completion; or
4. Surgical sterilization (vasectomy) of male partner at least 6 months prior to study.
10. To be considered of non-childbearing potential, females should be surgically sterilized (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 2 months prior to study) or be post-menopausal and at least 3 years since last menses.
11. Males with female partners of childbearing potential must use contraception through study completion.
12. Ability to safely lie flat for 90 min for magnetic resonance-positron emission tomography (MR-PET) procedures in the opinion of the Investigator.
13. Patients must also have a genotype associated with a high or mixed affinity translocator protein (TSPO) (Ala/Ala or Ala/Thr) and ability to safely undergo MR-PET scans based on the opinion of the Investigator.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Dependence on invasive or non-invasive ventilation, defined as being unable to lay supine without it, unable to sleep without it, or continuous daytime use; presence of tracheostomy at screening; or presence of diaphragm pacing system at screening.
2. Exposure to any experimental treatment for ALS within the last 30 days or five half-lives, whichever is longer.
3. Treatment within 12 months with immunomodulator or immunosuppressant agent (including but not limited to cyclophosphamide, cyclosporine, interferon-a, interferon-ß-1a, rituximab, alemtuzumab, azathioprine, etanercept, infliximab, adalimumab, certolizumab, golimumab, anakinra, rilonacept, secukinumab, tocilizumab, mycophenolate mofetil, methotrexate, cell-depleting agents, total lymphoid irradiation, dimethyl fumarate). Treatment with intravenous immunoglobulin (IVIG) within 2 months. Non-steroidal anti-inflammatory drugs (NSAIDs) are acceptable.
4. Exposure at any time to any cell or gene therapies under investigation for the treatment of ALS.
5. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other opportunistic infections; or major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks.
6. Live-attenuated vaccines within 30 days before dosing. Subjects must agree to forego live-attenuated vaccines throughout the study, including 60 days after the last dose of study drug.
7. History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
8. History of one or more of the following: cardiac insufficiency (New York Heart Association [NYHA] III/IV), uncontrolled cardiac arrhythmias, unstable ischemic heart disease, or uncontrolled hypertension (systolic blood pressure > 170 mmHg or diastolic blood pressure > 110 mmHg).
9. History of myocardial infarction, or cerebrovascular accident.
10. Unstable pulmonary, renal, hepatic, endocrine or hematologic disease.
11. Autoimmune disease, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to rheumatoid arthritis.
12. Evidence of active malignant disease, malignancies diagnosed within the previous 5 years, or breast cancer diagnosed within the previous 5 years (except skin cancers other than melanoma).
13. History of human immunodeficiency virus infection or other immunodeficiency illness.
14. Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days.
15. History of drug abuse (not including marijuana use) or alcoholism within the past 12 months.
16. Significant neuromuscular disease other than ALS.
17. Other ongoing disease that may cause neuropathy, such as toxin exposure, dietary deficiency, uncontrolled diabetes, hyperthyroidism, cancer, systemic lupus erythematosus or other connective diseases, infection with HIV, hepatitis B virus (HBV), or hepatitis C (HCV), Lyme disease, multiple myeloma, Waldenström's macroglobulinemia, amyloid, and hereditary neuropathy.
18. Pregnancy or breastfeeding.
19. Deprivation of freedom by administrative or court order.
20. Any contraindication to undergo magnetic resonance imaging (MRI) studies such as history of a cardiac pacemaker or pacemaker wires; metallic particles in the body; vascular clips in the head; prosthetic heart valves; or severe claustrophobia.
21. Unwilling or unable to discontinue benzodiazepine usage [other than lorazepam (Ativan®), clonazepam (Klonopin®), or zolpidem (Ambien®)] for one day prior to and during scanning.
22. Research imaging-related radiation exposure exceeds current institutional Radiology Department guidelines

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/09/2019
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
12/07/2021
Actual
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment postcode(s) [1] 0 0
4006 - Herston

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Implicit Bioscience
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jan Agosti, MD
Address 0 0
Implicit Bioscience Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03474263