In-Progress and Completed Trials
Clinical Studies
Clinical studies offer insight into what causes ALS and how the disease works.
Study of [11C]CPPC to Assess the Safety and Tolerability in Patients With ALS
Principal Investigator: Nicholas Maragakis, M.D.
Contact: Betsy Mosmiller | 410-502-0495
Route of Administration: Intravenous single dose injection
Length of Study: 6 weeks
This is a Phase 1 study of safety and tolerability of an investigational radiotracer drug called [5-cyano-N-(4-(4-[11C]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide] ([11C]CPPC). A radiotracer is a substance that chemically marks certain structures in the body. In this case, [11C]CPPC highlights structures expressing colony stimulating factor receptor (CSF1R), a receptor that is expressed on microglial cells. A safety and tolerability study is looking to see if there are any unanticipated, possibly harmful, effects of the use of the radiotracer in humans. However, ultimately, the investigators would like to know if this drug can be used to make better images of the brain for patients with amyotrophic lateral sclerosis (ALS), which could help doctors better understand the disease and help take care of patients with ALS. This study will use a radiotracer to look for a chemical receptor which ALS patients have more of in the brain. After receiving the radiotracer, participants' brains will be scanned with a positron emission tomography (PET) imaging machine.
CHAMPION
A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Multicenter Study with an Open-Label Extension to Evaluate the Efficacy and Safety of Ravulizumab in Patients with Amyotrophic Lateral Sclerosis (ALS)
Status: Completed
Principal Investigator: Jeffrey Rothstein, M.D., Ph.D.
Contact: Betsy Mosmiller | 410-502-0495
Ravulizumab (developed by Alexion Pharmaceuticals) is being investigated as a potential new therapy to slow progression of ALS. Ravulizumab is being developed to block complement activity in patients with ALS, which should help lower the immune reaction. The complement system is part of your immune system which fights against infections. In patients with ALS, abnormal complement activity is present, which may cause damage to the structures in the body that are responsible for neuromuscular transmission (how the brain sends signals to the muscles).
CENTAUR
AMX0035 in Patients with Amyotrophic Lateral Sclerosis
Status: Completed
Principal Investigator: Jeffrey Rothstein, M.D., Ph.D.
Contact: Betsy Mosmiller | 410-502-0495
AMX0035 is a combination therapy designed to reduce neuronal death through blockade of key cellular death pathways originating in the mitochondria and endoplasmic reticulum (ER). This clinical trial was designed to demonstrate that treatment is safe, tolerable, and able to slow decline in function as measured by the ALSFRS-R. The trial also assessed the effects of AMX0035 on muscle strength, vital capacity, and biomarkers of ALS including markers of neuronal death and neuroinflammation.
Assessment of Olfactory Dysfunction as a Potential Biomarker in Amyotrophic Lateral Sclerosis
Status: Completed
Principal Investigator: Nicholas J. Maragakis, M.D.
Contact: Betsy Mosmiller | 410-502-0495
Although there are several candidate biomarkers for ALS, none have been found to be applicable to therapy development or to predict disease progression at the time of diagnosis. Even the El Escorial criteria stage at the time of diagnosis inconsistently correlates with the disease’s progression. New biomarkers are necessary in order to shorten delay in diagnosis, initiate treatment sooner, and predict prognosis. The goal of this project was to test the possibility of using olfactory dysfunction (also known as hyposmia) as a biomarker of diagnosis or prognosis. Its ease to implement in clinic, lack of discomfort to the patient, and low cost make it an attractive candidate. Olfactory dysfunction has been found in patients with neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease, and frontotemporal dementia (FTD). Interestingly, olfactory impairment has been shown to predict the degree of cognitive impairment associated with PD. A cohort study found that worse baseline olfaction in patients with PD was associated with higher rates of cognitive decline. This project sought to conduct a pilot study to assess the potential use of olfactory dysfunction as a viable biomarker for ALS.
Answer ALS: Individualized Initiative for ALS Discovery
Status: Completed
Principal Investigator: Nicholas J. Maragakis, M.D.
Contact: Betsy Mosmiller | 410-502-0495
This initiative created a large repository of induced pluripotent stem cells (iPSC), bio-fluid samples (blood and spinal fluid (optional)), and cell lines for ALS gene identification. These were combined carefully with collected measures of the pattern of the symptoms people with ALS have and how these change over time. The clinical and biological samples from over 1000 patients and controls is available to the research public free of charge.
Methodology Study of Novel Electrophysiological, Physical, and Imaging Outcome Measures to Assess the Progression of Amyotrophic Lateral Sclerosis
Status: Completed
Principal Investigator: Nicholas J. Maragakis, M.D.
Contact: Betsy Mosmiller | 410-502-0495
This study looked at new methods of measuring ALS symptoms over time to see if these new approaches are better at detecting changes than the currently used methods. The methods that are found to be the most valuable in this study will be considered for use in future ALS clinical studies. The methods for measuring ALS symptoms that were used in this study include electrophysiological (i.e. the electrical properties of cells and tissues) tests, muscle strength tests, lung function tests, questionnaires about ALS status.
In addition, this study looked to find biomarkers linked to certain aspects of ALS that differ between individuals in order to help target future therapies to the patients’ most likely to benefit. Biomarkers are naturally occurring substances in the body. Examples of biomarkers are proteins, parts of proteins, or ribonucleic acid ([RNA], which tells the cells in your body which proteins to produce). Biomarkers can be found in your blood, spinal fluid, and tissue.
Understanding Clinical Phenotype and Collecting Biomarker Samples in C9ORF72 ALS
Status: Completed
Principal Investigator: Jeffrey Rothstein, M.D., Ph.D.
Contact: Betsy Mosmiller | 410-502-0495
This research study was performed to better understand a specific form of Amyotrophic Lateral Sclerosis (ALS) caused by a mutation (or abnormality) of the C9ORF72 gene. This mutation is the most common genetic cause of ALS, and is present in 40% of ALS patients with a family history of ALS and 5-10% of ALS patients without a family history of ALS.
Therapeutic Studies
HEALEY ALS PLATFORM TRIAL
Status: Active, Not Currently Enrolling
Route of Administration: Varies with Regime
Length of Study: 6 Months
Principal Investigator: Nicholas J. Maragakis, M.D.
Contact: Betsy Mosmiller ([email protected])
More information on clinicaltrials.gov: NCT04297683
The HEALEY ALS Platform Trial is a perpetual, multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS. This trial is designed as a perpetual platform trial. This means that there is a single master protocol dictating the conduct of the trial. In this trial, multiple investigational products for ALS will be tested simultaneously or sequentially. Each investigational product will be tested in a regimen. Each regimen consists of a placebo-controlled trial, meaning that the active investigational product and matching placebo will be tested in each regimen.
A Phase 1 Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB105 Administered Intrathecally to Adults with Amyotrophic Lateral Sclerosis with or Without Poly-CAG Expansion in the Ataxin-2 Gene
Status: Active, Enrolling
Route of Administration: Intrathecal (Lumbar Puncture)
Length of Study: ~ 6 Months
Principal Investigator: Jeffrey D. Rothstein, M.D., Ph.D.
Contact: Alpa Uchil, MPH, MSN, CRNP ( ([email protected])
More information on clinicaltrials.gov: NCT04494256
This research is being done to find out about the safety, tolerability and pharmacokinetics (PK) of the study drug BIIB105, administered intrathecally (into your spinal fluid) in adult subjects with ALS with or without a mutation in the Ataxin-2 Gene. PK looks at the level of the study drug in your body and what happens to this level over time from the moment that it is given to you up to the point at which it is completely eliminated from your body. It is studied by measuring the amount of study drug that gets into your blood, urine and cerebrospinal fluid after you take the study drug. Cerebrospinal fluid (CSF) is the fluid around the spinal cord. Subjects will be assigned to one of seven cohorts, depending on their ALS genetic status.
Himalaya/ ACT16970
A Phase 2, Multicenter , Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of SAR44320 in Adult Participants with Amyotrophic Lateral Sclerosis, Followed by an Open-Label Extension
Route of Administration: Oral
Length of Study: ~24 weeks + optional 1.5 year open label extension
Principal Investigator: Nicholas J. Maragakis, M.D.
This double-blinded study evaluates twice daily (BID) oral doses of SAR443820 compared to placebo in a 2:1 ratio. The double-blinded portion of this trial continues for 24 weeks. After this, participants will enter the open-label period in which all participants will receive SAR443820 20mg for up to 1.5 years. Patients who enroll in this trial are approved to continue taking their standard of care medications, but cannot begin a new ALS medication during the first 24 weeks.
SAR443820 is a drug being developed by Sanofi US Services Inc. to slow down the disease progression of ALS by acting on a protein inside cells (RIPK1) involved in the regulation of inflammation and cell death.
CALICO
A Randomized, Double-Blind, Placebo-Controlled Study to Assess Safety, Tolerability, and Pharmacokinetics Following Multiple Doses of ABBV-CLS-7262 in Subjects with Amyotrophic Lateral Sclerosis Followed by an Active Treatment Extension
Status: Active, Not Enrolling
Route of Administration: Oral
Length of Study: ~52 Weeks
Principal Investigator: Nicholas J. Maragakis, M.D.
ABBV-CLS-7262 is an investigational study drug targeting a key stress pathway shown to be overactive in people with ALS. The aim of this drug is to suppress the stress pathway and the harmful consequences associated with its overactivation. This is a two-part study: Part one is a 4-week, placebo-controlled, double-blind, randomized period. Participants will be randomly assigned to one of three groups. Two will get the study drug at different dosages, and the third will get a placebo.
Part two of this study, lasting approximately 48 weeks, is an active drug extension in which all participants will receive ABBV-CLS-7262 at the dosage they were assigned in part one. If the participant received placebo in part one, they will now receive ABBV-CLS-7262 at a dosage equal to the placebo.
ORAL EDARAVONE
A Phase 3b Multicenter, Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Oral Edaravone Administered for a Period of 48 Weeks in Subjects with Amyotrophic Lateral Sclerosis (ALS) (MT-1186-A02)
Status: Active, Not Enrolling
Route of Administration:Oral/Liquid
Length of Study: ~58 weeks
Principal Investigator: Jeffrey D. Rothstein M.D., Ph.D.
The intravenous form of edaravone has been approved by the FDA as a treatment for ALS since 2017. Its commercial name is Radicava. This study is to test if the oral version (a liquid solution you swallow) is safe and well tolerated in patients with ALS. Its effects will be compared in two different ways. One group will be given the study drug every day during the trial, and the other will be given the drug and a placebo on alternating cycles. (First cycle: 14 days of drug and 14 days of placebo. Second-twelfth cycles: 10 days of drug and 18 days of placebo). Neither you nor the study team will know to which group you are assigned.
A Phase 2a Study of TPN-101 in Patients With C9ORF72 ALS/FTD
Status: Active, Not Enrolling
Route of Administration: Oral
Length of Study: ~24 Weeks + UP TO 24 Weeks Optional Open Label Extension
Principal Investigator: Jeffrey D. Rothstein, M.D., Ph.D.
This is a Phase 2 study for ALS patients who carry the C9ORF72 gene mutation. Patients will receive investigational study drug TPN-101 once daily for 24 weeks followed by an open label extension.
The main outcome is to assess the safety and tolerability of TPN-101 in patients with C9ORF72 amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Other measures such as the pharmacokinetics of the study drug in the plasma and cerebrospinal fluid will also be assessed. The clinical effect of TPN-101 will be measures by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R).
Study of Safety, Tolerability, and Biological Activity of LAM-002A in C9ORF72-Associated Amyotrophic Lateral Sclerosis
Status: Active, Enrolling
Route of Administration: Oral
Length of Study: ~12 Weeks + UP TO 28 Weeks Optional Open Label Extension
Principal Investigator: Jeffrey D. Rothstein M.D., Ph.D.
This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled, biomarker- driven clinical trial to evaluate the safety, tolerability, and biological effect of LAM-002A in adults diagnosed with ALS who are confirmed to carry the Chromosome 9 Open Reading Frame 72 (C9ORF72) gene mutation (C9ALS). Participants will receive either standard of care plus LAM-002A or standard of care and placebo (randomized 2:1) for the first 12 weeks of the study (Core Study). LAM-002A will be administered as oral capsules 125 mg BID (250 mg total daily dose). The LAM-002A dose may be reduced to 100 mg BID (200 mg total daily dose) if adverse effects develop. Participants who complete the first 12 weeks on treatment will be eligible to receive active drug for the remainder of the study [Open Label Extension (OLE)] up to Week 24, with a Week 28 telephone phone call planned 28 days after the last dose of study drug.
BIIB100
A Phase 1, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB100 Administered Orally to Adult Participants with Amyotrophic Lateral Sclerosis.
Status: Completed
Principal Investigator: Nicholas J. Maragakis, M.D.
Contact: Betsy Mosmiller | 410-502-0495
Route of Administration: Oral
Length of Study: ~6 weeks
This is a first in human trial for this drug being studied for ALS. The main focus of this study is to show that BIIB100 will cause no harm to humans. In animal studies, BIIB100 was found to slow neurodegeneration and protect neurons from further degeneration. There will be 5 cohorts with 8 subjects in each cohort across 10 sites in the US. The first cohort will get the lowest dose and each additional cohort will get an ascending dose until the target dose is reached. Each person will get one oral dose of BIIB100, one time. 1 out of every 4 subjects will receive a placebo instead of BIIB100. This study requires a 4 day, 3 night stay in the hospital for drug administration and careful monitoring.
REFALS
Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients with ALS
Status: Completed
Principal Investigator: Nicholas J. Maragakis, M.D.
Contact: Betsy Mosmiller | 410-502-0495
Animal and human studies have shown that levosimendan may be useful to improve the muscle strength of the diaphragm and thereby the breathing function for patients with ALS. If ALS patients get increased breathing function, their overall well-being and function may be increased.
Levosimendan (Simdax®) is currently approved as a medication given through a vein for heart failure. It is approved by the regulatory authorities in 60 countries. Simdax® is not available on the market in the United States. In this study, levosimendan was tested for ALS, given as a capsule (to be taken orally). It is not approved by the FDA, but they gave permission for levosimendan to be used in this study.
A Phase 1 Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB078 Administered Intrathecally to Adults with C9ORF72-Associated Amyotrophic Lateral Sclerosis
Status: Completed
Principal Investigator: Jeffrey Rothstein, M.D., Ph.D.
Contact: Betsy Mosmiller | 410-502-0495
Route of Administration: Intrathecal
Length of Study: 6 months + optional open label extension
This research was done to find out about the safety, tolerability and pharmacokinetics (PK) of a range of the study drug BIIB078, administered intrathecally (into the spine) in adult subjects with ALS. PK looks at the level of the study drug in your body and what happens to this level over time from the moment that it is given to you up to the point at which it is completely eliminated from your body. It is studied by measuring the amount of study drug that gets into your blood, urine and cerebrospinal fluid after you take the study drug. Cerebrospinal fluid (CSF) is the fluid around the spinal cord.
This study was for patients who have a known mutation in the C9ORF72 gene. The study drug BIIB078, is an antisense therapy meant to specifically reduce the toxicity of the expanded C9ORF72 gene.
A Single-Ascending-Dose Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Patients with Amyotrophic Lateral Sclerosis
Status: Completed
Principal Investigator: Jeffrey Rothstein, M.D., Ph.D., Brett Morrison, M.D., Ph.D. and Andrea Markl Corse, M.D.
Contact: Betsy Mosmiller | 410-502-0495
GDC-0134 is a drug investigated by the Genentech company as a potential new therapy to prevent nerve cell death in patients with ALS. The purpose of this study was to evaluate the safety and pharmacokinetics of GDC-0134 in patients with Amyotrophic Lateral Sclerosis (ALS). This was a double-blind, placebo controlled study in which patients were randomly assigned to the study drug or a placebo.
A Phase 2 Pharmacodynamic Study of Ezogabine on Neuronal Excitability in Amyotrophic Lateral Sclerosis
Status: Completed
Principal Investigator: Nicholas J. Maragakis, M.D.
Contact: Betsy Mosmiller | 410-502-0495
A motor neuron is a type of cell in the nervous system that can make muscles move. One of the major disease features of ALS is the progressive death of motor neurons. Past research has shown that the motor neurons of ALS patients may be producing more electrical activity than motor neurons of people without ALS, and that this extra electrical activity tires the neurons and contributes to their death. This research study was done to find out whether the drug ezogabine would lower motor neuron activity in people with ALS. It was also done to determine whether the drug is tolerable and safe for patients with ALS.
About 120 participants with ALS and 72 healthy control volunteers (people without an ALS diagnosis) took part in this research study at about 12 centers across the United States.
Trial of Resistance and Endurance Exercise in Amyotrophic Lateral Sclerosis
Status: Completed
Principal Investigator: Nicholas J. Maragakis, M.D.
Contact: Betsy Mosmiller | 410-502-0495
ALS is a neurodegenerative disorder with no known cure. Exercise and activity, in some form, are part of nearly every patient’s daily life and the question about whether it is safe or beneficial to exercise is an often asked question by ALS patients—yet few data exist on this topic. This pilot trial was designed to be the first step in rigorously addressing the role of resistance, endurance, and range of motion exercises in ALS. We anticipate that the data gathered in this study will aid in the design of a larger efficacy study and eventually the inclusion of recommendations for exercise in an ALS practice parameter.