Status:
WITHDRAWN
IC14 for Rapidly Progressive Amyotrophic Lateral Sclerosis (ALS)
Lead Sponsor:
Implicit Bioscience
Conditions:
Amyotrophic Lateral Sclerosis
Eligibility:
All Genders
18-80 years
Phase:
PHASE2
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: bef...
Detailed Description
This is an open-label, biomarkers-driven study. Patients with rapidly progressive ALS will be assigned to the following dose regimen of IC14: • 4 mg/kg intravenously on Day 1, followed by 2 mg/kg da...
Eligibility Criteria
Inclusion
- 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
- serum albumin ≥ 2.8 g/dL
- 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.
- 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.
- Males with female partners of childbearing potential must use contraception through study completion.
- Ability to safely lie flat for 90 min for magnetic resonance-positron emission tomography (MR-PET) procedures in the opinion of the Investigator.
- 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
- 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.
- Significant neuromuscular disease other than ALS.
- 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.
- Pregnancy or breastfeeding.
- Deprivation of freedom by administrative or court order.
- 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.
- Unwilling or unable to discontinue benzodiazepine usage \[other than lorazepam (Ativan®), clonazepam (Klonopin®), or zolpidem (Ambien®)\] for one day prior to and during scanning.
- Research imaging-related radiation exposure exceeds current institutional Radiology Department guidelines
Key Trial Info
Start Date :
September 1 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 12 2021
Estimated Enrollment :
Patients enrolled
Trial Details
Trial ID
NCT03474263
Start Date
September 1 2019
End Date
July 12 2021
Last Update
June 24 2020
Active Locations (1)
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1
Royal Brisbane & Women's Hospital
Herston, Queensland, Australia, 4006