Platform Trial to Assess the Efficacy of Multiple Drugs in Amyotrophic Lateral Sclerosis (ALS)

Launched by STICHTING TRICALS FOUNDATION · Aug 21, 2023

Keywords

ClinConnect Summary

This clinical trial is studying the effectiveness of various drugs for people with Amyotrophic Lateral Sclerosis (ALS), a progressive disease that affects nerve cells in the brain and spinal cord. The trial is currently looking for participants aged 18 and older who have been diagnosed with ALS. To be eligible, participants must be able to understand the trial and follow its procedures. They can be on a stable dose of a medication called riluzole, which is often used for ALS, but must have been on it for at least 30 days before joining the study.

If you decide to participate, you'll be part of a research study where you may receive one of the new drugs being tested or a placebo (a harmless substitute that does not contain the drug). Throughout the study, you'll be monitored closely, and your participation will help researchers learn more about how these drugs can help manage ALS. It’s important to note that certain health conditions and medications may prevent someone from joining, so be sure to discuss any concerns with your doctor.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. ≥ 18 years at the time of screening.
• • 2. Diagnosis of ALS according to the revised El Escorial criteria (possible, probable-laboratory supported, probable or definite).
• • 3. Capable of providing informed consent and complying with trial procedures, including randomization to sub-studies.
• • 4. TRICALS risk profile \> -6.0 and \< -2.0 \*\*
• • 5. The use of riluzole will be permitted during the study. Subjects taking riluzole must be on a stable dose for at least 30 days prior to the baseline visit, or stopped taking riluzole at least 30 days prior to the baseline visit.
• • 6. Women of childbearing potential\* must have a negative pregnancy test at baseline and be non-lactating.
• • 7. Men must agree to practice contraception for the duration of the trial and for at least 3 months after last dose of study drug.
• • 8. Men must not plan to father a child or to provide sperm for donation for the duration of the trial and 3 months after the last dose of study drug.
• • 9. Women must not be able to become pregnant (e.g. post-menopausal\*\*\*, surgically sterile or using effective birth control methods) for the duration of the study. Effective contraceptives are defined as having a failure rate of less than 1% per year when used consistently and correctly and, when applicable, in accordance with the product label, including: abstinence, hormonal contraception, intrauterine device in place for ≥ 3 months Appendix 1). Women of childbearing potential must have a negative pregnancy test at baseline, and be non-lactating. Women who are pregnant or are actively seeking to become pregnant, and women of reproductive potential who are not using effective contraceptives are excluded.
• Exclusion Criteria:
• 1. Laboratory Criteria at baseline:
• • ALT (alanine transaminase) ≥ 5 times upper limit of normal (ULN)
• • AST (aspartate aminotransferase) ≥ 3 times ULN
• • Bilirubin ≥ 1.5 times ULN
• • Estimated glomerular filtration rate (eGFR) \< 50 mL / min / 1.73 m2 based on Cystatin C, if not available eGFR can also be calculated based on creatinine clearance.
• • Platelet concentration of \< 100 x109 per L
• • Absolute neutrophil count of \< 1x109 per L
• • Haemoglobin \< 100 g/L (\<6.2 mmol/L)
• • Amylase \& lipase ≥ 2 times ULN (suspected pancreatitis)
• • Lactate ≥ 2 times ULN (suspected lactate acidosis)
• • 2. Moderate to severe hepatic impairment according to Child-Pugh classification (Class B or higher; score ≥ 7). Child-Pugh classification is based on bilirubin, albumin, International Normalized Ratio (INR) and presence of encephalopathy or ascites.
• • 3. Participation in any other investigational drug trial or using investigational drug (within 30 days prior to screening).
• • 4. Hypothyroidism unresponsive to thyroid hormone supplementation.
• • 5. Subjects using non-invasive ventilation (NIV, ≥22 h per day) or having a tracheostomy.
• • 6. Subjects taking edaravone within 30 days prior to screening. Edaravone is approved by the FDA, but remains an investigational product in Europe and Australia.
• • 7. Clinically significant history of unstable or severe cardiac (e.g. congestive heart failure, coronary insufficiency and arrhythmias), oncological, hepatic or renal disease, neuromuscular diseases, significant pulmonary disorder or other medically significant illness.
• • 8. Drug or alcohol abuse.
• • 9. Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the screening visit. This exclusion criterion is based on a prior psychiatric diagnosis that is unstable as determined by the subject's treating Psychiatrist.
• • 10. Presence of frontotemporal dementia which prevents informed consent.
• Lithium carbonate study-specific exclusion criteria:
• • 1. Patients heterozygous or homozygous for the A-allele of rs12608932 (UNC13A)
• • 2. Known allergy or hypersensitivity to lithium, or its excipients, or to the components of the placebo.
• • 3. Brain injury with posttraumatic epilepsy or neurologic deficit, excluding a concussion in the medical history. Brain infarction is an exclusion criterion, a transient ischemic attack is not.
• • 4. Addison disease.
• • 5. Patients with the following co-medication: antipsychotics, digoxin and calcium antagonists, carbamazepine, methyldopa, verapamil and diltiazem.
• • 6. Brugada Syndrome or family history of Brugada Syndrome.
• • 7. Plasma sodium \<120 mmol/L