IC14 for Treatment of Amyotrophic Lateral Sclerosis

NCT03508453 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: ALS03
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Motor Neuron Disease; Amyotrophic Lateral Sclerosis

Keywords

monoclonal antibody

Outcome Measures

Primary Outcomes (3)

• Neurofilament (biomarker)

  Treatment-related change in concentration of neurofilament (picograms per milliliter)

  12 weeks

• Urinary p75 neurotrophin receptor (biomarker)

  Treatment-related change in concentration of urinary p75 neurotrophin receptor (nanograms per milligram creatinine)

  12 weeks

• Monocyte CD14 receptor occupancy

  Treatment-related change in percent monocyte receptor occupancy

  12 weeks

Secondary Outcomes (9)

• Functional status

  12 weeks

• Respiratory function

  12 weeks

• Muscle function

  12 weeks

• Quality of life measured by ALSSQOL

  12 weeks

• Cognitive and behavioural assessment

  12 weeks

Study Arms (2)

IC14 (monoclonal anti-CD14 antibody)

ACTIVE COMPARATOR

IC14 4 mg/kg intravenously twice weekly for 12 weeks

Biological: IC14

Placebo

PLACEBO COMPARATOR

Placebo intravenously twice weekly for 12 weeks

Other: Placebo

Interventions

IC14 BIOLOGICAL

Monoclonal antibody against CD14

IC14 (monoclonal anti-CD14 antibody)

Placebo OTHER

sterile normal saline for injection prepared to be identical to study drug

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Implicit Bioscience: lead

Study Sites (1)

Royal Brisbane and Women's Hospital

Herston, Queensland, 4006, Australia

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Robert D Henderson, MBBS

  Royal Brisbane & Women's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Pharmacy preparation of identical-appearing placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Placebo-Controlled

Study Record Dates

• First Submitted: April 16, 2018
• First Posted: April 25, 2018
• Study Start: August 15, 2021
• Primary Completion: May 15, 2023
• Study Completion: December 15, 2023
• Last Updated: May 5, 2026

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)