Amyotrophic Lateral SclerosisPhase 2NCT03508453
IC14 for Treatment of Amyotrophic Lateral Sclerosis
A Phase 2 study testing IC14 in people with Amyotrophic Lateral Sclerosis and Motor Neuron Disease, run by Implicit Bioscience at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease
- What is being tested?
- IC14
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteAustralia
- Study dates
- 15 Aug 2021to 15 Dec 2023
- Phase
- Phase 2
- 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
- Signed informed consent prior to initiation of any study-specific procedures.
- Familial or sporadic MND defined as clinically possible, probable, or definite by Awaji-Shima Consensus Recommendations.
- Rapidly progressive MND as defined by a decline of 3 or more points in the ALSFRS-R score during the prior 3 months.
- 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 edaravone or on a stable dose of riluzole or edaravone for at least 3 months prior to screening visit.
- 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
- 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.
- Able to give informed consent and able to comply with all study visits and all study procedures.
Who cannot join
- 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, 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.
- 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.
- 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.
- 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:
- 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.
- 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 2, Randomised, Double-Blind, Placebo-Controlled Study of IC14 for Treatment of Patients With Rapidly Progressive Motor Neuron Disease
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.
Read the detailed description
This will be a placebo-controlled, double-blind, parallel-group comparison.
Fifty patients with rapidly progressive ALS will be randomised to receive one of the following regimens:
- IC14 4 mg/kg given intravenously twice weekly for 12 weeks; or
- Identical-appearing placebo given intravenously twice weekly for 12 weeks. There will be an interim safety review by an independent Data Safety Monitoring Board after the initial 20 subjects have completed 4 weeks and 8 weeks of treatment. Study observation will continue until 12 weeks after the last dose of study drug.
The primary endpoint is:
- Treatment-related change in disease biomarker profiles [e.g., neurofilaments (Nf), urinary p75 neurotrophin receptor (p75NTR), cytokines, and soluble CD14].
The secondary endpoints are:
- Safety, tolerability and lack of immunogenicity of IC14.
- Treatment-related change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).
- Treatment-related change in respiratory function by seated forced vital capacity (FVC) parameters.
- Treatment-related change in inspiratory muscle strength by sniff nasal pressure (SNP) test.
- Treatment-related change in quality of life by the ALS Specific Quality of Life-Revised (ALSSQOL-R) score.
- Treatment-related change in cognitive function by Edinburgh Cognitive and Behavioural Assessment (ECAS) score.
- Treatment-related changes stratified by disease severity and prognostic indicators.
- Peak serum IC14 concentration following administration of the initial dose and peak serum concentration following a course of treatment.
- Area under the serum IC14 concentration versus time curve (AUC) following administration of the initial dose and following a course of treatment.
- Being tested
- IC14, Placebo
- Keywords
- monoclonal antibody
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IC14Biological
Monoclonal antibody against CD14
PlaceboOther
sterile normal saline for injection prepared to be identical to study drug
| Study group | Role | What they receive |
|---|---|---|
| IC14 (monoclonal anti-CD14 antibody) | Active comparator | IC14 4 mg/kg intravenously twice weekly for 12 weeks Receives: Biological: IC14 |
| Placebo | Placebo comparator | Placebo intravenously twice weekly for 12 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurofilament (biomarker)
Treatment-related change in concentration of neurofilament (picograms per milliliter)
Measured: 12 weeks
Urinary p75 neurotrophin receptor (biomarker)
Treatment-related change in concentration of urinary p75 neurotrophin receptor (nanograms per milligram creatinine)
Measured: 12 weeks
Monocyte CD14 receptor occupancy
Treatment-related change in percent monocyte receptor occupancy
Measured: 12 weeks
Secondary outcomes (9)
Functional status
Treatment-related change in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale [0 (worst) to 48 (best)]
Measured: 12 weeks
Respiratory function
Treatment-related change in percent normal Forced Vital Capacity [0% (worst) to 100%(best)]
Measured: 12 weeks
Muscle function
Treatment-related change in percent normal Sniff Nasal Pressure [0% (worst) to 100% (best)]
Measured: 12 weeks
Quality of life measured by ALSSQOL
Treatment-related change in Amyotrophic Lateral Sclerosis Specific Quality of Life - Revised questionnaire [0 (worst) to 460 (best)]
Measured: 12 weeks
Cognitive and behavioural assessment
Treatment-related change in Edinburgh Cognitive and Behavioural Assessment Score [0(worst) to 136 (best)]
Measured: 12 weeks
Maximum plasma concentration (Cmax)
Maximum serum IC14 concentration (micrograms per milliliter)
Measured: 12 weeks
Area under the curve
Area under the curve for serum IC14 (microgram x hr/mL)
Measured: 12 weeks
Immunogenicity
Development of human anti-monoclonal antibodies following treatment
Measured: 16 weeks
Adverse events (safety, tolerability)
Incidence of treatment-emergent adverse events (safety, tolerability) classified by MedDRA
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2018
- Study start15 Aug 2021 (estimated)
- Primary completion15 May 2023 (estimated)
- Study completion15 Dec 2023 (estimated)
Why it stopped: No participants enrolled in study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, Double-Blind, Placebo-Controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Implicit Bioscience
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert D Henderson, MBBS, Study chair, Royal Brisbane & Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03508453
- Sponsor's protocol ID
- ALS03
- Status last verified
- Feb 2021
- First submitted
- 16 Apr 2018
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomised, Double-Blind, Placebo-Controlled Study of IC14 for Treatment of Patients With Rapidly Progressive Motor Neuron Disease
- ClinicalTrials.gov ID
- NCT03508453
- Acronym / sponsor ID
- ALS03
- Keywords
- monoclonal antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No participants enrolled in study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Implicit BioscienceIndustry (pharma, biotech, devices)
- Study start
- 15 Aug 2021 (estimated)
- Primary completion
- 15 May 2023 (estimated)
- Study completion
- 15 Dec 2023 (estimated)
- First posted
- 25 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.
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.
Detailed description
This will be a placebo-controlled, double-blind, parallel-group comparison.
Fifty patients with rapidly progressive ALS will be randomised to receive one of the following regimens:
- IC14 4 mg/kg given intravenously twice weekly for 12 weeks; or
- Identical-appearing placebo given intravenously twice weekly for 12 weeks. There will be an interim safety review by an independent Data Safety Monitoring Board after the initial 20 subjects have completed 4 weeks and 8 weeks of treatment. Study observation will continue until 12 weeks after the last dose of study drug.
The primary endpoint is:
- Treatment-related change in disease biomarker profiles [e.g., neurofilaments (Nf), urinary p75 neurotrophin receptor (p75NTR), cytokines, and soluble CD14].
The secondary endpoints are:
- Safety, tolerability and lack of immunogenicity of IC14.
- Treatment-related change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).
- Treatment-related change in respiratory function by seated forced vital capacity (FVC) parameters.
- Treatment-related change in inspiratory muscle strength by sniff nasal pressure (SNP) test.
- Treatment-related change in quality of life by the ALS Specific Quality of Life-Revised (ALSSQOL-R) score.
- Treatment-related change in cognitive function by Edinburgh Cognitive and Behavioural Assessment (ECAS) score.
- Treatment-related changes stratified by disease severity and prognostic indicators.
- Peak serum IC14 concentration following administration of the initial dose and peak serum concentration following a course of treatment.
- Area under the serum IC14 concentration versus time curve (AUC) following administration of the initial dose and following a course of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, Double-Blind, Placebo-Controlled
| Arm | Type | Receives |
|---|---|---|
| IC14 (monoclonal anti-CD14 antibody) | Active comparator | Biological: IC14IC14 4 mg/kg intravenously twice weekly for 12 weeks |
| Placebo | Placebo comparator | Other: PlaceboPlacebo intravenously twice weekly for 12 weeks |
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 MND defined as clinically possible, probable, or definite by Awaji-Shima Consensus Recommendations.
- Rapidly progressive MND as defined by a decline of 3 or more points in the ALSFRS-R score during the prior 3 months.
- First symptoms of MND within 3 years of informed consent.
- Age between 18 and 75 years at time of informed consent.
Key exclusion criteria (19 listed)
- 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, 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.
- 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.
- 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.
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 |
|---|---|---|
| IC14Monoclonal antibody against CD14 | Biological | IC14 (monoclonal anti-CD14 antibody) |
| Placebosterile normal saline for injection prepared to be identical to study drug | Other | Placebo |
Primary outcome
Neurofilament (biomarker)
Time frame: 12 weeks
Treatment-related change in concentration of neurofilament (picograms per milliliter)
Urinary p75 neurotrophin receptor (biomarker)
Time frame: 12 weeks
Treatment-related change in concentration of urinary p75 neurotrophin receptor (nanograms per milligram creatinine)
Monocyte CD14 receptor occupancy
Time frame: 12 weeks
Treatment-related change in percent monocyte receptor occupancy
9 secondary outcomes
Functional status
Time frame: 12 weeks
Respiratory function
Time frame: 12 weeks
Muscle function
Time frame: 12 weeks
Quality of life measured by ALSSQOL
Time frame: 12 weeks
Cognitive and behavioural assessment
Time frame: 12 weeks
Maximum plasma concentration (Cmax)
Time frame: 12 weeks
Area under the curve
Time frame: 12 weeks
Immunogenicity
Time frame: 16 weeks
Adverse events (safety, tolerability)
Time frame: 16 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- 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 study chair
Royal Brisbane & 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 2 study testing IC14 in people with Amyotrophic Lateral Sclerosis and Motor Neuron Disease, 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 19 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: withdrawn, as of the sponsor's last update on 5 May 2026. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
Neurofilament (biomarker) (time frame: 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 May 2026.