IC14 for Treatment of Amyotrophic Lateral Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03508453
• Date of registration: 16/04/2018
• Prospective Registration: Yes
• Primary sponsor: Implicit Bioscience
• Public title: IC14 for Treatment of Amyotrophic Lateral Sclerosis
• Scientific title: A Phase 2, Randomised, Double-Blind, Placebo-Controlled Study of IC14 for Treatment of Patients With Rapidly Progressive Motor Neuron Disease
• Date of first enrolment: August 15, 2019
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03508453
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Australia

Contacts

• Name: Robert D Henderson, MBBS
• Affiliation: Royal Brisbane & Women's Hospital

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Signed informed consent prior to initiation of any study-specific procedures.

2. Familial or sporadic MND defined as clinically possible, probable, or definite by
Awaji-Shima Consensus Recommendations.

3. Rapidly progressive MND as defined by a decline of 3 or more points in the ALSFRS-R
score during the prior 3 months.

4. First symptoms of MND within 3 years of informed consent.

5. Age between 18 and 75 years at time of informed consent.

6. Seated Forced Vital Capacity (FVC) = 65% of predicted value.

7. Not taking riluzole or edaravone or on a stable dose of riluzole or edaravone for at
least 3 months prior to screening visit.

8. 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

9. 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.

10. 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.

11. Males with female partners of childbearing potential must use contraception through
study completion.

12. Able to give informed consent and able to comply with all study visits and all study
procedures.

Exclusion Criteria:

1. 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.

2. Treatment with a drug or device within the last 30 days that has not received
regulatory approval.

3. Treatment within 12 months with immunomodulator or immunosuppressant agent (including
but not limited to cyclophosphamide, cyclosporine, interferon-a, interferon-ß-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.

4. 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.

5. 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.

6. History of severe allergic or anaphylactic reactions to human, humanized or murine
monoclonal antibodies.

7. 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.

8. Pregnancy or breastfeeding.

9. Deprivation of freedom by administrative or court order.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Amyotrophic Lateral Sclerosis

Motor Neuron Disease

Intervention(s)

Other: Placebo

Biological: IC14

Primary Outcome(s)

Monocyte CD14 receptor occupancy [Time Frame: 12 weeks]

Neurofilament (biomarker) [Time Frame: 12 weeks]

Urinary p75 neurotrophin receptor (biomarker) [Time Frame: 12 weeks]

Secondary Outcome(s)

Functional status [Time Frame: 12 weeks]

Maximum plasma concentration (Cmax) [Time Frame: 12 weeks]

Adverse events (safety, tolerability) [Time Frame: 16 weeks]

Area under the curve [Time Frame: 12 weeks]

Immunogenicity [Time Frame: 16 weeks]

Respiratory function [Time Frame: 12 weeks]

Quality of life measured by ALSSQOL [Time Frame: 12 weeks]

Muscle function [Time Frame: 12 weeks]

Cognitive and behavioural assessment [Time Frame: 12 weeks]

Secondary ID(s)

ALS03

Source(s) of Monetary Support

Please refer to primary and secondary sponsors