IC14 for Rapidly Progressive Amyotrophic Lateral Sclerosis (ALS)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03474263
• Date of registration: 09/03/2018
• Prospective Registration: Yes
• Primary sponsor: Implicit Bioscience
• Public title: IC14 for Rapidly Progressive Amyotrophic Lateral Sclerosis (ALS)
• Scientific title: A Phase 2a, Open-Label Biomarker Study of IC14 for the Treatment of Patients With
• Date of first enrolment: September 1, 2019
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03474263
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Australia, United States

Contacts

• Name: Jan Agosti, MD
• Affiliation: Implicit Bioscience Ltd.

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Capable of providing informed consent and informed consent form signed prior to
initiation of any study-specific procedures.

2. Familial or sporadic ALS defined as clinically possible, probable, or definite by El
Escorial Criteria.

3. 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).

4. Upper Motor Neuron Burden Score of = 25 (out of 45) at screening

5. First symptoms of ALS within 3 years of the screening visit

6. Age between 18 and 80 years at the time of the screening visit.

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:

1. absolute neutrophil count = 1500/µL

2. lymphocyte count < 6000/µL

3. platelet count = 150,000/µL

4. hemoglobin = 11 g/dL

5. creatinine clearance = 60 mL/min

6. alanine transaminase (ALT) and/or aspartate transaminase (AST) = 3x upper limits
of normal (ULN)

7. total bilirubin = 1.5x ULN

8. serum albumin = 2.8 g/dL

9. Females of childbearing potential should be using and committed to continue using one
of the following acceptable birth control methods:

1. Sexual abstinence (inactivity) for 1 month prior to screening through study
completion; or

2. Intrauterine device (IUD) in place for at least 3 months prior to study through
study completion; or

3. Stable hormonal contraception for at least 3 months prior to study through study
completion; or

4. 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. Ability to safely lie flat for 90 min for magnetic resonance-positron emission
tomography (MR-PET) procedures in the opinion of the Investigator.

13. Patients must also have a genotype associated with a high or mixed affinity
translocator protein (TSPO) (Ala/Ala or Ala/Thr) and ability to safely undergo MR-PET
scans based on the opinion of the Investigator.

Exclusion Criteria:

1. 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.

2. Exposure to any experimental treatment for ALS within the last 30 days or five
half-lives, whichever is longer.

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, cell-depleting agents, total lymphoid irradiation, dimethyl
fumarate). Treatment with intravenous immunoglobulin (IVIG) within 2 months.
Non-steroidal anti-inflammatory drugs (NSAIDs) are acceptable.

4. Exposure at any time to any cell or gene therapies under investigation for the
treatment of ALS.

5. 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.

6. 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.

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

8. 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).

9. History of myocardial infarction, or cerebrovascular accident.

10. Unstable pulmonary, renal, hepatic, endocrine or hematologic disease.

11. Autoimmune disease, mixed connective tissue disease, scleroderma, polymyositis, or
significant systemic involvement secondary to rheumatoid arthritis.

12. 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).

13. History of human immunodeficiency virus infection or other immunodeficiency illness.

14. Unstable psychiatric illness defined as psychosis or untreated major depression within
90 days.

15. History of drug abuse (not including marijuana use) or alcoholism within the past 12
months.

16. Significant neuromuscular disease other than ALS.

17. 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.

18. Pregnancy or breastfeeding.

19. Deprivation of freedom by administrative or court order.

20. Any contraindication to undergo magnetic resonance imaging (MRI) studies such as
history of a cardiac pacemaker or pacemaker wires; metallic particles in the body;
vascular clips in the head; prosthetic heart valves; or severe claustrophobia.

21. Unwilling or unable to discontinue benzodiazepine usage [other than lorazepam
(Ativan®), clonazepam (Klonopin®), or zolpidem (Ambien®)] for one day prior to and
during scanning.

22. Research imaging-related radiation exposure exceeds current institutional Radiology
Department guidelines



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Amyotrophic Lateral Sclerosis

Intervention(s)

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

Primary Outcome(s)

Urinary p75 neurotrophin receptor [Time Frame: one month]

Glial Activation [Time Frame: one month]

Serum neurofilament [Time Frame: one month]

Secondary Outcome(s)

Pharmacodynamics [Time Frame: one month]

Immunogenicity [Time Frame: six weeks]

Incidence of Treatment-Emergent Adverse Events (Safety, Tolerability) [Time Frame: six weeks]

Peak Plasma Concentration of IC14 [Time Frame: one month]

Secondary ID(s)

ALS02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors