IC14 for Rapidly Progressive Amyotrophic Lateral Sclerosis (ALS)

NCT03474263 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: ALS02
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with rapidly progressive ALS will be assigned to IC14 intravenously on Day 1-4. This 4-day course will be repeated on Days 8-11. Patients will all undergo MR-PET scans at two time points: before treatment onset and after the last treatment cycle. This scan will measure areas of ALS disease activity and assess response to IC14 treatment. MR-PET scans will be compared to historical controls.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Motor Neurone Disease (MND); Amyotrophic Lateral Sclerosis (ALS)

Outcome Measures

Primary Outcomes (3)

• Glial Activation

  Glial activation measured in the motor region measured by \[11C\]-PBR28 positron emission tomography (PET). Studies have shown this marker localizes to areas of glial activation and correlates with disease progression and outcomes.

  one month

• Serum neurofilament

  Serum neurofilament is a biomarker that has been shown to correlate with ALS severity

  one month

• Urinary p75 neurotrophin receptor

  Urinary p75 neurotrophin receptor is a biomarker that has been shown to correlate with ALS severity

  one month

Secondary Outcomes (4)

• Incidence of Treatment-Emergent Adverse Events (Safety, Tolerability)

  six weeks

• Immunogenicity

  six weeks

• Peak Plasma Concentration of IC14

  one month

• Pharmacodynamics

  one month

Study Arms (1)

IC14 (monoclonal anti-CD14 antibody)

EXPERIMENTAL

Biologic: IC14 (monoclonal anti-CD14 antibody) 4 mg/kg intravenously followed by IC14 2 mg/kg intravenously on Days 2-4. This four-day cycle will be repeated on Days 8-11.

Biological: Biologic: IC14 (monoclonal antibody against human CD14)

Interventions

Biologic: IC14 (monoclonal antibody against human CD14) BIOLOGICAL

IC14 intravenous infusion daily for four days on two successive weeks then MR-PET Scan evaluation for impact on glial activation.

Also known as: Anti-CD14

IC14 (monoclonal anti-CD14 antibody)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of providing informed consent and informed consent form signed prior to initiation of any study-specific procedures.
• Familial or sporadic ALS defined as clinically possible, probable, or definite by El Escorial Criteria.
• Rapidly progressive ALS defined by the Revised ALS Functional Rating Scale (ALSFRS-R) slope ≥1 (48 minus ALSFRS-R score at screening / disease duration in months ≥ 1).
• Upper Motor Neuron Burden Score of ≥ 25 (out of 45) at screening
• First symptoms of ALS within 3 years of the screening visit
• Age between 18 and 80 years at the time of the screening visit.
• 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 ≥ 1500/µL
• lymphocyte count \< 6000/µL
• platelet count ≥ 150,000/µL
• hemoglobin ≥ 11 g/dL
• creatinine clearance ≥ 60 mL/min
• alanine transaminase (ALT) and/or aspartate transaminase (AST) ≤ 3x upper limits of normal (ULN)
• total bilirubin ≤ 1.5x ULN

You may not qualify if:

• Dependence on invasive or non-invasive 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.
• Exposure to any experimental treatment for ALS within the last 30 days or five half-lives, whichever is longer.
• 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, cell-depleting agents, total lymphoid irradiation, dimethyl fumarate). Treatment with intravenous immunoglobulin (IVIG) within 2 months. Non-steroidal anti-inflammatory drugs (NSAIDs) are acceptable.
• Exposure at any time to any cell or gene therapies under investigation for the treatment of ALS.
• 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 intravenous (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 60 days after the last dose of study drug.
• History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
• 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 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.

Sponsors & Collaborators

• Implicit Bioscience: lead

Study Sites (1)

Royal Brisbane & Women's Hospital

Herston, Queensland, 4006, Australia

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Jan Agosti, MD

  Implicit Bioscience Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label Biomarkers-Driven Study Historical controls

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: March 22, 2018
• Study Start: September 1, 2019
• Primary Completion: April 12, 2021
• Study Completion: July 12, 2021
• Last Updated: May 5, 2026

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)