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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03474263
Ethics application status
Date submitted
9/03/2018
Date registered
22/03/2018
Date last updated
14/03/2019

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
Other interventions - 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.


Other interventions: 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
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Glial Activation - Glial activation measured in the motor region measured by [11C]-PBR28 positron emission tomography (PET). Studies have shown this marker localizes to areas of glial activation and correlates with disease progression and outcomes.
Timepoint [1] 0 0
one month
Primary outcome [2] 0 0
Serum neurofilament - Serum neurofilament is a biomarker that has been shown to correlate with ALS severity
Timepoint [2] 0 0
one month
Primary outcome [3] 0 0
Urinary p75 neurotrophin receptor - Urinary p75 neurotrophin receptor is a biomarker that has been shown to correlate with ALS severity
Timepoint [3] 0 0
one month
Secondary outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events (Safety, Tolerability) - Adverse event reporting
Timepoint [1] 0 0
six weeks
Secondary outcome [2] 0 0
Immunogenicity - Human anti-monoclonal antibodies
Timepoint [2] 0 0
six weeks
Secondary outcome [3] 0 0
Peak Plasma Concentration of IC14 - Peak Plasma Concentration (Cmax) of IC14
Timepoint [3] 0 0
one month
Secondary outcome [4] 0 0
Pharmacodynamics - Monocyte CD14 saturation
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
Gender
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
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
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)
QLD
Recruitment hospital [1] 0 0
Royal Brigham & 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
Patients with rapidly progressive ALS will be assigned to IC14 intravenously on Day 1-4. This
4-day course will be repeated on Days 8-11. Patients will all undergo MR-PET scans at two
time points: before treatment onset and after the last treatment cycle. This scan will
measure areas of ALS disease activity and assess response to IC14 treatment. MR-PET scans
will be compared to historical controls.
Trial website
https://clinicaltrials.gov/show/NCT03474263
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

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03474263