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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
Scientific title
A Phase 1b, Open-Label, Dose-Escalation, Safety and Pharmacokinetic Study of IC14 in Motor Neurone Disease
Secondary ID [1] 0 0
ALS01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Motor Neuron Disease 0 0
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 - 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
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of treatment-emergent adverse events (safety, tolerability)
Timepoint [1] 0 0
one month
Secondary outcome [1] 0 0
Treatment-related change in ALSFRS-R functional scale
Timepoint [1] 0 0
one month
Secondary outcome [2] 0 0
Respiratory function
Timepoint [2] 0 0
one month
Secondary outcome [3] 0 0
Muscle function
Timepoint [3] 0 0
one month
Secondary outcome [4] 0 0
Quality of life measured by ALSSQOL
Timepoint [4] 0 0
one month
Secondary outcome [5] 0 0
Patient-reported outcome
Timepoint [5] 0 0
one month
Secondary outcome [6] 0 0
Maximum Plasma Concentration (Cmax)
Timepoint [6] 0 0
one month
Secondary outcome [7] 0 0
Area Under the Curve (AUC)
Timepoint [7] 0 0
one month
Secondary outcome [8] 0 0
Monocyte CD14 Receptor Occupancy
Timepoint [8] 0 0
one month
Secondary outcome [9] 0 0
Urinary p75 neurotrophin receptor (biomarker)
Timepoint [9] 0 0
one month
Secondary outcome [10] 0 0
Neurofilament (biomarker)
Timepoint [10] 0 0
one month
Secondary outcome [11] 0 0
Anti-drug antibodies
Timepoint [11] 0 0
one month

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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.

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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/12/2018
Sample size
Target
Accrual to date
Final
10
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
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Royal Brisbane and Women's Hospital
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03487263
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Robert D. Henderson, MBBS
Address 0 0
Royal Brisbane and 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