Dose-Escalation, Safety and Pharmacokinetic Study of IC14 in Motor Neurone Disease

NCT03487263 | Completed Phase 1 FDA Drug

• 1 other identifier: ALS01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Motor Neuron Disease; Amyotrophic Lateral Sclerosis

Keywords

motor neurone disease; amyotrophic lateral sclerosis; IC14 [anti-CD14 (cluster of differentiation 14) monoclonal antibody]; monoclonal antibody; anti-CD14

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events (safety, tolerability)

  Number of participants with treatment-emergent adverse events (safety, tolerability) classified by MedDRA

  one month

Secondary Outcomes (11)

• Treatment-related change in ALSFRS-R functional scale

  one month

• Respiratory function

  one month

• Muscle function

  one month

• Quality of life measured by ALSSQOL

  one month

• Patient-reported outcome

  one month

Study Arms (2)

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

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

Biological: IC14

Interventions

IC14 BIOLOGICAL

chimeric monoclonal antibody against human IC14

Also known as: monoclonal antibody against CD14

IC14 dose level 1; IC14 dose level 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Implicit Bioscience: lead
• Royal Brisbane and Women's Hospital: collaborator

Study Sites (1)

Royal Brisbane and Women's Hospital

Herston, Queensland, 4006, Australia

Location

Related Publications (1)

• 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.

  PMID: 34678870 BACKGROUND

MeSH Terms

Conditions

Motor Neuron Disease; Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Robert D. Henderson, MBBS

  Royal Brisbane and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, dose-escalation, safety and pharmacokinetic

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: April 4, 2018
• Study Start: October 1, 2017
• Primary Completion: April 18, 2018
• Study Completion: December 30, 2018
• Last Updated: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)