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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03508453




Registration number
NCT03508453
Ethics application status
Date submitted
16/04/2018
Date registered
25/04/2018
Date last updated
15/05/2020

Titles & IDs
Public title
IC14 for Treatment of Amyotrophic Lateral Sclerosis
Scientific title
A Phase 2, Randomised, Double-Blind, Placebo-Controlled Study of IC14 for Treatment of Patients With Rapidly Progressive Motor Neuron Disease
Secondary ID [1] 0 0
ALS03
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 0 0
Motor Neuron Disease 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 - IC14
Other interventions - Placebo

Active Comparator: IC14 (monoclonal anti-CD14 antibody) - IC14 4 mg/kg intravenously twice weekly for 12 weeks

Placebo Comparator: Placebo - Placebo intravenously twice weekly for 12 weeks


Other interventions: IC14
Monoclonal antibody against CD14

Other interventions: Placebo
sterile normal saline for injection prepared to be identical to study drug

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Neurofilament (biomarker) - Treatment-related change in concentration of neurofilament (picograms per milliliter)
Timepoint [1] 0 0
12 weeks
Primary outcome [2] 0 0
Urinary p75 neurotrophin receptor (biomarker) - Treatment-related change in concentration of urinary p75 neurotrophin receptor (nanograms per milligram creatinine)
Timepoint [2] 0 0
12 weeks
Primary outcome [3] 0 0
Monocyte CD14 receptor occupancy - Treatment-related change in percent monocyte receptor occupancy
Timepoint [3] 0 0
12 weeks
Secondary outcome [1] 0 0
Functional status - Treatment-related change in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale [0 (worst) to 48 (best)]
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
Respiratory function - Treatment-related change in percent normal Forced Vital Capacity [0% (worst) to 100%(best)]
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
Muscle function - Treatment-related change in percent normal Sniff Nasal Pressure [0% (worst) to 100% (best)]
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Quality of life measured by ALSSQOL - Treatment-related change in Amyotrophic Lateral Sclerosis Specific Quality of Life - Revised questionnaire [0 (worst) to 460 (best)]
Timepoint [4] 0 0
12 weeks
Secondary outcome [5] 0 0
Cognitive and behavioural assessment - Treatment-related change in Edinburgh Cognitive and Behavioural Assessment Score [0(worst) to 136 (best)]
Timepoint [5] 0 0
12 weeks
Secondary outcome [6] 0 0
Maximum plasma concentration (Cmax) - Maximum serum IC14 concentration (micrograms per milliliter)
Timepoint [6] 0 0
12 weeks
Secondary outcome [7] 0 0
Area under the curve - Area under the curve for serum IC14 (microgram x hr/mL)
Timepoint [7] 0 0
12 weeks
Secondary outcome [8] 0 0
Immunogenicity - Development of human anti-monoclonal antibodies following treatment
Timepoint [8] 0 0
16 weeks
Secondary outcome [9] 0 0
Adverse events (safety, tolerability) - Incidence of treatment-emergent adverse events (safety, tolerability) classified by MedDRA
Timepoint [9] 0 0
16 weeks

Eligibility
Key inclusion criteria
1. Signed informed consent prior to initiation of any study-specific procedures.

2. Familial or sporadic MND defined as clinically possible, probable, or definite by
Awaji-Shima Consensus Recommendations.

3. Rapidly progressive MND as defined by a decline of 3 or more points in the ALSFRS-R
score during the prior 3 months.

4. First symptoms of MND within 3 years of informed consent.

5. Age between 18 and 75 years at time of informed consent.

6. Seated Forced Vital Capacity (FVC) = 65% of predicted value.

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:

- absolute neutrophil count = 1.5 x 109/L

- lymphocyte count < 6.0 x 109/L

- platelet count = 150 x 109/L

- hemoglobin = 110 g/L

- eGFR = 40 mL/min/1.73 m2

- ALT and/or AST = 2x ULN

- total bilirubin = 1.5x ULN

- serum albumin = 28 g/L

9. Females of childbearing potential should be using and committed to continue using one
of the following acceptable birth control methods:

- Sexual abstinence (inactivity) for 1 month prior to screening through study
completion; or

- Intrauterine device (IUD) in place for at least 3 months prior to study through
study completion; or

- Stable hormonal contraception for at least 3 months prior to study through study
completion; or

- 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. Able to give informed consent and able to comply with all study visits and all study
procedures.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Dependence on mechanical 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. Treatment with a drug or device within the last 30 days that has not received
regulatory approval.

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, haematopoietic stem cell transplantation, anti-sense drugs,
gene therapy, cell-depleting agents, total lymphoid irradiation). Treatment with
intravenous immunoglobulin within 2 months or dimethyl fumarate within 3 months.
Non-steroidal anti-inflammatory drugs are acceptable.

4. 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 IV antibiotics within 4 weeks.

5. Live-attenuated vaccines within 30 days before dosing. Subjects must agree to forego
live-attenuated vaccines throughout the study, including 12 weeks after the last dose
of study drug.

6. History of severe allergic or anaphylactic reactions to human, humanized or murine
monoclonal antibodies.

7. Presence of any of the following clinical conditions:

- 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).

- History of venous thromboembolic disease within 12 months, myocardial infarction,
or cerebrovascular accident.

- Unstable pulmonary, renal, hepatic, endocrine or hematologic disease.

- Autoimmune disease, mixed connective tissue disease, scleroderma, polymyositis,
or significant systemic involvement secondary to rheumatoid arthritis.

- 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).

- History of human immunodeficiency virus infection or other immunodeficiency
illness.

- Unstable psychiatric illness defined as psychosis or untreated major depression
within 90 days.

- History of drug abuse (not including marijuana use) or alcoholism within the past
12 months.

- Significant neuromuscular disease other than MND.

- 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.

8. Pregnancy or breastfeeding.

9. Deprivation of freedom by administrative or court order.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
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 Brisbane and 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
Fifty patients with amyotrophic lateral sclerosis that is progressing rapidly will be
randomized to receive either the monoclonal antibody IC14 or placebo to be given
intravenously over two hours twice weekly for 12 weeks. Blood and urine tests will be done to
measure biomarkers in order to evaluate clinical response and to monitor for safety. Other
evaluations include patient questionnaires about function, quality of life and mental
function; pulmonary function test; and sniff nasal pressure.
Trial website
https://clinicaltrials.gov/show/NCT03508453
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Robert D Henderson, MBBS
Address 0 0
Royal Brisbane & Women's Hospital
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/NCT03508453