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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03487263
Registration number
NCT03487263
Ethics application status
Date submitted
9/03/2018
Date registered
4/04/2018
Date last updated
14/03/2019
Titles & IDs
Public title
Dose-Escalation, Safety and Pharmacokinetic Study of IC14 in Motor Neurone Disease
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Scientific title
A Phase 1b, Open-Label, Dose-Escalation, Safety and Pharmacokinetic Study of IC14 in Motor Neurone Disease
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Secondary ID [1]
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ALS01
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Motor Neuron Disease
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Amyotrophic Lateral Sclerosis
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Condition category
Condition code
Neurological
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Neurodegenerative diseases
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - IC14
Experimental: IC14 dose level 1 - For the initial 3 patients: intravenous IC14 at a dosage of 2 mg/kg on Study Day 1, then 1 mg/kg once daily on Study Days 3-5 for 4 total doses
Experimental: IC14 dose level 2 - For the subsequent 7 patients: intravenous IC14 at a dosage of 4 mg/kg/day on Day 1, followed by IC14 2 mg/kg/day on Days 2-4
Other interventions: IC14
chimeric monoclonal antibody against human IC14
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Intervention code [1]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Incidence of treatment-emergent adverse events (safety, tolerability)
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Assessment method [1]
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Number of participants with treatment-emergent adverse events (safety, tolerability) classified by MedDRA
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Timepoint [1]
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one month
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Secondary outcome [1]
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Treatment-related change in ALSFRS-R functional scale
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Assessment method [1]
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Treatment-related change in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) [0 (worst) to 48 (best)]
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Timepoint [1]
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one month
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Secondary outcome [2]
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Respiratory function
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Assessment method [2]
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Treatment-related change in percent normal Forced Vital Capacity [0% (worst) to 100% (best)]
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Timepoint [2]
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one month
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Secondary outcome [3]
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Muscle function
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Assessment method [3]
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Treatment-related change in percent normal Sniff Nasal Pressure [0% (worst) to 100% (best)]
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Timepoint [3]
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one month
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Secondary outcome [4]
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Quality of life measured by ALSSQOL
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Assessment method [4]
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Treatment-related change in Amyotrophic Lateral Sclerosis Specific Quality of Life - Revised (ALSSQOL-R) [0 (worst) to 460 (best)]
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Timepoint [4]
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one month
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Secondary outcome [5]
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Patient-reported outcome
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Assessment method [5]
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Treatment-related change Edinburgh Cognitive and Behavioural Assessment Score (ECAS) [0 (worst) to 136 (best)]
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Timepoint [5]
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one month
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Secondary outcome [6]
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Maximum Plasma Concentration (Cmax)
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Assessment method [6]
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Maximum serum IC14 concentration (micrograms per milliliter)
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Timepoint [6]
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one month
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Secondary outcome [7]
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Area Under the Curve (AUC)
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Assessment method [7]
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Area Under the Curve for serum IC14 (microgram x hr/mL)
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Timepoint [7]
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one month
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Secondary outcome [8]
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Monocyte CD14 Receptor Occupancy
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Assessment method [8]
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Treatment-related change in percent monocyte CD14 receptor occupancy as a pharmacodynamic marker
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Timepoint [8]
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one month
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Secondary outcome [9]
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Urinary p75 neurotrophin receptor (biomarker)
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Assessment method [9]
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Treatment-related change in urinary concentration of urinary p75 neurotrophin receptor (NTR) (nanograms per milligram creatinine)
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Timepoint [9]
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one month
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Secondary outcome [10]
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Neurofilament (biomarker)
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Assessment method [10]
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Treatment-related change in concentration of neurofilament (picograms per milliliter)
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Timepoint [10]
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one month
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Secondary outcome [11]
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Anti-drug antibodies
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Assessment method [11]
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Development of human anti-monoclonal antibodies following treatment
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Timepoint [11]
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one month
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Eligibility
Key inclusion criteria
A patient must fulfill all of the following criteria to be eligible for enrollment:
1. Signed informed consent prior to initiation of any study-specific procedures.
2. Familial or sporadic motor neurone disease (MND) defined as clinically possible,
probable, or definite by Awaji-Shima Consensus Recommendations.
3. First symptoms of MND within 3 years of informed consent.
4. Age between 18 and 75 years at time of informed consent.
5. Seated Forced Vital Capacity (FVC) = 65% of predicted value.
6. Not taking riluzole or on a stable dose of riluzole for at least 4 weeks prior to
screening visit.
7. Adequate bone marrow reserve, renal and liver function:
- absolute neutrophil count = 1500/µL
- lymphocyte count < 48%
- platelet count = 150,000/µL
- hemoglobin = 11 g/dL
- Estimated glomerular filtration rate (eGFR) >= 40 mL/min/1.73 m2
- Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) = 2x upper
imit of normal (ULN), total bilirubin = 1.5x ULN
- serum albumin = 2.8 g/dL
8. 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.
9. 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.
10. Males with female partners of childbearing potential must use contraception through
study completion.
11. Medically safe to have lumbar puncture to collect cerebrospinal fluid.
12. Able to give informed consent and able to comply with all study visits and all study
procedures.
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Minimum age
18
Years
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Maximum age
75
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
A patient fulfilling any of the following criteria at screening is to be excluded from
enrollment in the study:
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).
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. History of severe allergic or anaphylactic reactions to human, humanized or murine
monoclonal antibodies.
6. Presence of any of the following clinical conditions:
- Bleeding diathesis or receipt of anticoagulants within 7 days (or any other
clinical condition that would, in the opinion of the investigator, place the
patient at increased risk during lumbar puncture).
- 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).
- Human immunodeficiency virus infection or other immunodeficiency illness.
- Unstable psychiatric illness defined as psychosis or untreated major depression
within 90 days.
- Drug abuse 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.
7. Pregnancy or breastfeeding.
8. Deprivation of freedom by administrative or court order.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Other
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/10/2017
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
30/12/2018
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Sample size
Target
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Accrual to date
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Final
10
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Recruitment in Australia
Recruitment state(s)
QLD
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Recruitment hospital [1]
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Royal Brisbane and Women's Hospital - Herston
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Recruitment postcode(s) [1]
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4006 - Herston
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Implicit Bioscience
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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Royal Brisbane and Women's Hospital
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
Ten patients with motor neurone disease (MND, also known as amyotrophic lateral sclerosis or
ALS) will be successively enrolled to one of two dose levels of IC14 (human chimeric
monoclonal anti-CD14) intravenously for four doses. Patients must be within 3 years of MND
diagnosis and have adequate respiratory function. Safety, tolerability, immunogenicity, and
PK/PD will be measured. To evaluate feasibility of the endpoints, additional endpoints of
ALSFRS-R, respiratory function tests, disease biomarkers and patient-reported outcomes will
be measured.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03487263
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Robert D. Henderson, MBBS
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Address
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Royal Brisbane and Women's Hospital
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03487263
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