Motor Neuron DiseasePhase 1NCT03487263
Dose-Escalation, Safety and Pharmacokinetic Study of IC14 in Motor Neurone Disease
A Phase 1 study testing IC14 in people with Motor Neuron Disease and Amyotrophic Lateral Sclerosis, run by Implicit Bioscience at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Motor Neuron Disease, Amyotrophic Lateral Sclerosis
- What is being tested?
- IC14
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteAustralia
- Study dates
- 1 Oct 2017to 30 Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A patient must fulfill all of the following criteria to be eligible for enrollment:
- Signed informed consent prior to initiation of any study-specific procedures.
- Familial or sporadic motor neurone disease (MND) defined as clinically possible, probable, or definite by Awaji-Shima Consensus Recommendations.
- First symptoms of MND within 3 years of informed consent.
- Age between 18 and 75 years at time of informed consent.
- Seated Forced Vital Capacity (FVC) ≥ 65% of predicted value.
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- Not taking riluzole or on a stable dose of riluzole for at least 4 weeks prior to screening visit.
- 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
- 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.
- 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.
- Males with female partners of childbearing potential must use contraception through study completion.
- Medically safe to have lumbar puncture to collect cerebrospinal fluid.
- Able to give informed consent and able to comply with all study visits and all study procedures.
Who cannot join
- A patient fulfilling any of the following criteria at screening is to be excluded from enrollment in the study:
- 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.
- Treatment with a drug or device within the last 30 days that has not received regulatory approval.
- Treatment within 12 months with immunomodulator or immunosuppressant agent (including but not limited to cyclophosphamide, cyclosporine, interferon-α, interferon-β-1a, rituximab, alemtuzumab, azathioprine, etanercept, infliximab, adalimumab, certolizumab, golimumab, anakinra, rilonacept, secukinumab, tocilizumab, mycophenolate mofetil, methotrexate, haematopoietic stem cell transplantation).
- 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.
- History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
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- 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.
- Pregnancy or breastfeeding.
- Deprivation of freedom by administrative or court order.
Trial locations and contacts
1 site in 1 country.
Australia1 site
Royal Brisbane and Women's Hospital
Herston, Queensland, 4006
About this study
Official title: A Phase 1b, Open-Label, Dose-Escalation, Safety and Pharmacokinetic Study of IC14 in Motor Neurone Disease
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.
Read the detailed description
The objectives of this study are to determine:
- The safety, tolerability and immunogenicity of IC14 in patients with motor neurone disease (MND).
- The pharmacokinetics and pharmacodynamics of IC14 in patients with MND.
- The preliminary effect of IC14 on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) in patients with MND.
- The preliminary effect of IC14 on forced vital capacity (FVC) and other clinical markers of disease severity in patients with MND.
- The preliminary effect of IC14 on patient-reported outcome measures.
- The preliminary effect of IC14 on disease biomarkers.
Ten patients with MND will be sequentially assigned to receive one of two dose regimens of IC14 in an unblinded manner:
- For the initial 3 patients: 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.
- For the subsequent 7 patients: IC14 at a dosage of 4 mg/kg on Study Day 1, then 2 mg/kg once daily on Study Days 2-4 for 4 total doses.
Study participation will continue until 28 days after the last dose of study drug.
- Being tested
- IC14
- Keywords
- motor neurone disease, amyotrophic lateral sclerosis, IC14 [anti-CD14 (cluster of differentiation 14) monoclonal antibody], monoclonal antibody, anti-CD14
- Medical subject headings
- Motor Neuron Disease, Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IC14Biological
Also called monoclonal antibody against CD14
chimeric monoclonal antibody against human IC14
| Study group | Role | What they receive |
|---|---|---|
| IC14 dose level 1 | Experimental | 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 Receives: Biological: IC14 |
| IC14 dose level 2 | Experimental | 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 Receives: Biological: IC14 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events (safety, tolerability)
Number of participants with treatment-emergent adverse events (safety, tolerability) classified by MedDRA
Measured: one month
Secondary outcomes (11)
Treatment-related change in ALSFRS-R functional scale
Treatment-related change in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) [0 (worst) to 48 (best)]
Measured: one month
Respiratory function
Treatment-related change in percent normal Forced Vital Capacity [0% (worst) to 100% (best)]
Measured: one month
Muscle function
Treatment-related change in percent normal Sniff Nasal Pressure [0% (worst) to 100% (best)]
Measured: one month
Quality of life measured by ALSSQOL
Treatment-related change in Amyotrophic Lateral Sclerosis Specific Quality of Life - Revised (ALSSQOL-R) [0 (worst) to 460 (best)]
Measured: one month
Patient-reported outcome
Treatment-related change Edinburgh Cognitive and Behavioural Assessment Score (ECAS) [0 (worst) to 136 (best)]
Measured: one month
Maximum Plasma Concentration (Cmax)
Maximum serum IC14 concentration (micrograms per milliliter)
Measured: one month
Area Under the Curve (AUC)
Area Under the Curve for serum IC14 (microgram x hr/mL)
Measured: one month
Monocyte CD14 Receptor Occupancy
Treatment-related change in percent monocyte CD14 receptor occupancy as a pharmacodynamic marker
Measured: one month
Urinary p75 neurotrophin receptor (biomarker)
Treatment-related change in urinary concentration of urinary p75 neurotrophin receptor (NTR) (nanograms per milligram creatinine)
Measured: one month
Neurofilament (biomarker)
Treatment-related change in concentration of neurofilament (picograms per milliliter)
Measured: one month
Anti-drug antibodies
Development of human anti-monoclonal antibodies following treatment
Measured: one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2018
- Study start1 Oct 2017
- Primary completion18 Apr 2018
- Study completion30 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Motor Neuron DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Open-label, dose-escalation, safety and pharmacokinetic
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Implicit Bioscience
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Royal Brisbane and Women's Hospital
- Responsible party
- Sponsor
- Investigators
- Robert D. Henderson, MBBS, Principal investigator, Royal Brisbane and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03487263
- Sponsor's protocol ID
- ALS01
- Status last verified
- Aug 2025
- First submitted
- 9 Mar 2018
- Last updated
- 20 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Henderson RD, Agosti JM, McCombe PA, Thorpe K, Heggie S, Heshmat S, Appleby MW, Ziegelaar BW, Crowe DT, Redlich GL. Phase 1b dose-escalation, safety, and pharmacokinetic study of IC14, a monoclonal antibody against CD14, for the treatment of amyotrophic lateral sclerosis. Medicine (Baltimore). 2021 Oct 22;100(42):e27421. doi: 10.1097/MD.0000000000027421.
PubMed 34678870
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Open-Label, Dose-Escalation, Safety and Pharmacokinetic Study of IC14 in Motor Neurone Disease
- ClinicalTrials.gov ID
- NCT03487263
- Acronym / sponsor ID
- ALS01
- Keywords
- motor neurone disease, amyotrophic lateral sclerosis, IC14 [anti-CD14 (cluster of differentiation 14) monoclonal antibody], monoclonal antibody, anti-CD14
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Implicit BioscienceIndustry (pharma, biotech, devices)
- Collaborators
- Royal Brisbane and Women's Hospital
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 18 Apr 2018 (actual)
- Study completion
- 30 Dec 2018 (actual)
- First posted
- 4 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The objectives of this study are to determine:
- The safety, tolerability and immunogenicity of IC14 in patients with motor neurone disease (MND).
- The pharmacokinetics and pharmacodynamics of IC14 in patients with MND.
- The preliminary effect of IC14 on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) in patients with MND.
- The preliminary effect of IC14 on forced vital capacity (FVC) and other clinical markers of disease severity in patients with MND.
- The preliminary effect of IC14 on patient-reported outcome measures.
- The preliminary effect of IC14 on disease biomarkers.
Ten patients with MND will be sequentially assigned to receive one of two dose regimens of IC14 in an unblinded manner:
- For the initial 3 patients: 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.
- For the subsequent 7 patients: IC14 at a dosage of 4 mg/kg on Study Day 1, then 2 mg/kg once daily on Study Days 2-4 for 4 total doses.
Study participation will continue until 28 days after the last dose of study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open-label, dose-escalation, safety and pharmacokinetic
| Arm | Type | Receives |
|---|---|---|
| IC14 dose level 1 | Experimental | Biological: IC14For 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 |
| IC14 dose level 2 | Experimental | Biological: IC14For 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Signed informed consent prior to initiation of any study-specific procedures.
- Familial or sporadic motor neurone disease (MND) defined as clinically possible, probable, or definite by Awaji-Shima Consensus Recommendations.
- First symptoms of MND within 3 years of informed consent.
- Age between 18 and 75 years at time of informed consent.
- Seated Forced Vital Capacity (FVC) ≥ 65% of predicted value.
Key exclusion criteria (20 listed)
- A patient fulfilling any of the following criteria at screening is to be excluded from enrollment in the study:
- 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.
- Treatment with a drug or device within the last 30 days that has not received regulatory approval.
- Treatment within 12 months with immunomodulator or immunosuppressant agent (including but not limited to cyclophosphamide, cyclosporine, interferon-α, interferon-β-1a, rituximab, alemtuzumab, azathioprine, etanercept, infliximab, adalimumab, certolizumab, golimumab, anakinra, rilonacept, secukinumab, tocilizumab, mycophenolate mofetil, methotrexate, haematopoietic stem cell transplantation).
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IC14Also: monoclonal antibody against CD14chimeric monoclonal antibody against human IC14 | Biological | IC14 dose level 1, IC14 dose level 2 |
Primary outcome
Incidence of treatment-emergent adverse events (safety, tolerability)
Time frame: one month
Number of participants with treatment-emergent adverse events (safety, tolerability) classified by MedDRA
11 secondary outcomes
Treatment-related change in ALSFRS-R functional scale
Time frame: one month
Respiratory function
Time frame: one month
Muscle function
Time frame: one month
Quality of life measured by ALSSQOL
Time frame: one month
Patient-reported outcome
Time frame: one month
Maximum Plasma Concentration (Cmax)
Time frame: one month
Area Under the Curve (AUC)
Time frame: one month
Monocyte CD14 Receptor Occupancy
Time frame: one month
Urinary p75 neurotrophin receptor (biomarker)
Time frame: one month
Neurofilament (biomarker)
Time frame: one month
Anti-drug antibodies
Time frame: one month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2025.
- Results publication: PubMed 34678870Henderson RD, Agosti JM, McCombe PA, Thorpe K, Heggie S, Heshmat S, Appleby MW, Ziegelaar BW, Crowe DT, Redlich GL. Phase 1b dose-escalation, safety, and pharmacokinetic study of IC14, a monoclonal antibody against CD14, for the treatment of amyotrophic lateral sclerosis. Medicine (Baltimore). 2021 Oct 22;100(42):e27421. doi: 10.1097/MD.0000000000027421.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert D. Henderson, MBBS principal investigator
Royal Brisbane and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IC14 in people with Motor Neuron Disease and Amyotrophic Lateral Sclerosis, run by Implicit Bioscience at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-emergent adverse events (safety, tolerability) (time frame: one month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03487263, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2025.