Clinical Trials and Studies at the Healey & AMG Center for ALS

Enrolling ALS Clinical Trials

These trials test potential new medications for ALS. Click on the individual trials listed below to learn more and reach out to the appropriate study coordinator. You can also download the Enrolling Clinical Trials Brochure to print or view later.

Trial of AMX0114 Phase 1

Sponsor: Amylyx Pharmaceuticals Full Trial Name: A Phase 1, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Antisense Oligonucleotide AMX0114 Administered to Adult Participants with Amyotrophic Lateral Sclerosis Trial Phase: 1 Trial Length: 25 weeks Participants: People 18 years or older with ALS. Drug to Placebo Ratio: 3:1 Target: CAPN2 RNA Science: AMX0114 is an investigational antisense oligonucleotide (ASO) medicine targeting the CAPN2 gene to reduce production of the Calpain-2 protein. There is evidence that calpain-2 is associated with processes known to cause neuronal injury and loss of axons which are attached to the motor neurons. By reducing the Calpain-2 protein this drug may slow disease progression. Administration: Lumbar puncture (needle inserted into spinal fluid in the lower spine to administer dose); 4 doses every 4 weeks with an additional lumbar puncture for collection at the end of the study Purpose: To evaluate the safety and tolerability of the study drug in ALS patients Principal Investigator: Dr. Sabrina Paganoni Enrollment Contacts: amx0114healey@mgb.org Lucy Lee, 617-643-7434 Anika Allen, 617-724-9196

Trial of BrainGate

Participants: People who have limited or no use of their hands, including people with ALS.

Full Trial Name: BrainGate: Feasibility Study of an Intracortical Neural Interface System for Persons With Tetraplegia

Patients who have weakness due to motor neuron disease such as amyotrophic lateral sclerosis (ALS) and have no or limited use of their hands are needed for an FDA regulated research study to evaluate a new technology which may allow an individual with quadriplegia to control a computer cursor and assistive devices, like a robotic arm, by thought. This study is invasive and requires surgery. Research sessions are run at participants’ residences, so to be eligible, participants must live within 3 hours drive of Boston, MA or Providence, RI. The clinical trial requires a commitment of 13 (thirteen) months. The study is being conducted by Dr. Leigh Hochberg at Massachusetts General Hospital.

Principal Investigator: Leigh Hochberg, MD, PhD
Enrollment Contacts: clinicaltrials@braingate.org, neurotechnology@mgh.harvard.edu

Trial of COYA-302 Phase 2

Sponsor: Coya Therapeutics

Full Trial Name: Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, 24-Week Study with Additional 24-Week Blinded Active Extension to Evaluate the Safety and Efficacy of COYA 302 for the Treatment of Amyotrophic Lateral Sclerosis (ALS)

Trial Phase: 2

Trial Length: 24-week placebo-controlled trial followed by 24-week extension

Participants: Adult participants (≥18 to ≤75 years of age) with sporadic or familial ALS

Drug to Placebo Ratio: 2:1

Target: Increase Regulatory T Cells (Tregs)

Science: Tregs which reduce inflammation are often present in fewer numbers in people with ALS. COYA 302 is a combination of interleukin-2 (IL-2) and a biosimilar candidate to abatacept. This investigational drug is expected to increase the function and number of Tregs while also directly reducing inflammation. Improving the efficacy of Tregs may reduce toxicity to the motor neurons and slow ALS progression.

Administration: Subcutaneous injection

1. Purpose: To study the safety and efficacy of COYA302 in participants with ALS

Principal Investigator: James Berry, MD, MPH

Enrollment Contacts: coya302healey@mgb.org
Sophie Cohen, 617-643-7828

Trial of Pridopidine Phase 3

Sponsor: Prilenia Therapeutics BV and Ferrer International, S.A.

Full Trial Name: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Pridopidine in Participants with Amyotrophic Lateral Sclerosis (ALS)

Phase: 3

Purpose of Trial: To evaluate if the investigational study drug (pridopidine) may slow disease progression and improve speech, breathing, and survival

Drug to Placebo Ratio: 3 drug to 2 placebo

Participants: Participants are aged 18–80, have been diagnosed with ALS, and have experienced first symptoms for no longer than 18 months.

Trial Length: 48-weeks placebo-controlled, followed by 48-week open label extension (OLE)

Target: Increase activation of the Sigma-1-Receptor (S1R)

Science: Pridopidine activates the Sigma-1 Receptor (S1R), a protein in nerve cells. By activating S1R, pridopidine may help protect nerve cells from damage and slow the neurodegeneration caused by ALS.

Administration: Hard gelatin capsule taken orally

Principal Investigator: Dr. Sabrina Paganoni, MD, PhD

Contact Information: mghpridopidinephase3healey@mgb.org
Julia Stein, 617-726-1398
Kimberly Lin, 617-724-3268

Trial of RAPA-501 Phase 2/3

Sponsor: Rapa Therapeutics, LLC Full Trial Name: Phase 2/3 Trial of Autologous Hybrid TREG/Th2 Cell Therapy (RAPA-501) for Amyotrophic Lateral Sclerosis Trial Phase: 2/3 Trial Length: Up to one year in person (5-8 visits); Two years of remote follow-up (8 visits) Drug to Placebo: Open Label (no placebo) Target: T-cells Science: In people with ALS, the body’s immune system becomes imbalanced, which is thought to contribute to the loss of motor neurons in the brain and spinal cord. Regulatory T-cells, a specific type of immune cell, reduce inflammation. Therefore, scientists believe that they could help to balance the immune system of people with ALS. The goal of this study is to utilize a modified version of Regulatory T-cells, called RAPA-501 cells, to reduce neuroinflammation and potentially slow ALS progression. This process involves: (1) harvesting T-cells from the participants own blood through a process called apheresis, (2) reprogramming the harvested T-cells in special cell culture conditions to become RAPA-501 cells, and (3) infusing the specialized RAPA-501 cells back into the participants bloodstream through an IV. Administration: (1) Apheresis (blood separation) to collect T-cells (2) Intravenous (IV) infusion of the specialized RAPA-501 cells Purpose: To learn more about the efficacy and safety of RAPA-501 cell therapy in people living with ALS Principal Investigator: James Berry, MD, MPH Enrollment Contacts:rapa501healey@mgb.org Megan Okoro, 617-643-6252 Kathryn Chew, 617-643-4968

Trial of Tofersen Phase 2

Full Trial Name: A Study to Evaluate the Biological Effects of Tofersen in Adults with Amyotrophic Lateral Sclerosis without Mutations in SOD1. Sponsor: Biogen Inc. Phase: 2 Drug to Placebo Ratio: Open label, no placebo Target: SOD1 protein Trial Length: Approximately 9 months, with the possibility to continue receiving tofersen for an indefinite period if the study doctor thinks it is helping you. Purpose: To evaluate the effect of tofersen on neurofilament light chain (NfL) in non-SOD1 ALS. Science: Tofersen is an FDA approved drug to treat SOD1-ALS, but it is not approved for the treatment of non-SOD1 ALS; therefore, it is an investigational product in this study. Tofersen is an antisense oligonucleotide that targets mutations in the SOD1 gene by reducing the production of toxic SOD1 proteins. Emerging data suggests that SOD1 is implicated in the pathogenesis of non-SOD1 ALS, specifically, misfolded wtSOD1 that is predicted to be neurotoxic. Given the demonstrated effects of tofersen in slowing SOD1-ALS, this study aims to test whether tofersen can also lower neurofilament in sporadic (non-SOD1) ALS population. Participants: People diagnosed with ALS without SOD1 or FUS mutations. Administration: Intrathecal injection via lumbar puncture. Principal Investigator: Suma Babu, MBBS, MPH Contact Information: tofersensporadichealey@mgb.org Miranda Durcan, 617-643-9550 Lucy Lee, 617-643-7434

Trial of Usnoflast Phase 2

Participants: Adults with ALS Drug to Placebo Ratio: 1:1:1 (Usnoflast : Usnoflast + Placebo: Placebo) Target: NLRP3 inflammasome Science: The study drug, Usnoflast, is a selective inhibitor that prevents the activation of the NLRP3 inflammasome pathway. This pathway is believed to contribute to ALS disease progression through activating proteins that lead to neuroinflammation and cell death. By targeting this pathway, the hope is to slow the loss of nerve cells and therefore disease progression. Administration: Participants will receive an oral dose of the study drug taken as 2 capsules twice a day. Participants will be asked to fast two hours before and after each dose. Lumbar Punctures: 3 optional Principal Investigator: Jennifer Morganroth, MD, MBA Contact Information: usnoflasthealey@mgb.org, (617) 724-3268 Kyle Molinari Shyanne Hill

Trial of VTx-002 Phase 1-2

Sponsor: VectorY Therapeutics B.V. Full Trial Name: A Phase 1/2 Study of the Safety and Tolerability of ICM VTx-002 in participants with ALS (PIONEER-ALS) Trial Phase: 1-2 Trial Length: Approximately 5 years. Year 1: 12 in-person visits and 4 remote visits. Years 2-5: 8 in-person (preferable) or remote visits Participants: People diagnosed with ALS without SOD1or FUS mutations Drug to Placebo Ratio: Open label, no placebo Target: TDP-43 protein clumps Science: Participants will receive a single injection into the intra-cisterna magna (at the base of the brain) of the disease-modifying gene therapy VTx-002. The goal of VTx-002 is to target clumps of TDP-43 protein, which are believed to contribute to cellular dysfunction and neuronal death. VTx-002 is delivered by a virus vector (harmless virus turned into a delivery tool that carries information into the cells). This study drug aims to break down TDP-43 clumps and restore their function to prevent disease progression. Administration: Intra-cisterna magna injection (at the base of the brain) performed by neurosurgeon Purpose: To assess the safety and tolerability of VTx-002 for the treatment of people with ALS Principal Investigator: Doreen Ho, MD Enrollment Contacts: pioneeralshealey@mgb.org Winifred Asigri, 617-724-5659 Megan Okoro, 617-643-6252

Enrolling Studies: Clinical Research to Understand ALS

These studies help researchers learn about changes to people with ALS over time. Click on the individual studies listed below to learn more and reach out to the appropriate study coordinator. You can also download two separate brochures, Biofluid Studies Brochure and Digital Observational & Biomarker Brochure to print or view later.

Study of ASSESS ALL ALS

Full Study Name: ASSESS ALL ALS – Longitudinal Biomarker Study for Symptomatic ALS and Healthy Control Participants Study Length: up to 2 years (7 in person or remote visits) Participants: People with ALS and healthy volunteers Biomarkers: Blood Purpose: To study people diagnosed with ALS and healthy participants to further our understanding of the disease and potential biomarkers of disease progression. The information collected in this study may contribute to future research and development of new treatments for ALS and similar neurological diseases. Principal Investigator: James Berry, MD, MPH Sponsor: National Institutes of Health and St. Joseph’s Hospital and Medical Center, Phoenix, AZ Enrollment Contact: mghassessallals@mgb.org Miranda Durcan, 617-643-9550 Read ASSESS ALL ALS Brochure

Study of ElectricALS

Full Trial Name: Electrical Impedance Myography via the Myolex mScan as an ALS Biomarker

Trial Length: 8-10 months

Participants: Diagnosed with ALS, 18+ years of age, symptom onset ≤ 36 months, Vital Capacity ≥ 50% of predicted capacity as measured by forced vital capacity, can identify a study partner for home visits

Purpose of Study: This study is being done to see how a device, the mScan, measures muscle changes over time in people living with ALS. This device uses Electrical Impedence Myography (EIM), which uses a very small, non-invasive (e.g. no needles), brief (about 6 seconds), and painless electrical current to measure the muscle tissue. We hope that this measurement can help with tracking disease progression and be used in the future to help understand how well treatments are working.

Study Assessments: EIM measurements will be taken with the mScan device at your regular clinic visits, 3-5 times over 8-10 months. Your study partner will also take mScan measurements twice a week at home. The ALS Functional Rating Scale-Revised (ALSFRS-R) will be completed weekly at home and then also at the in-person visits.

Principal Investigator: Sabrina Paganoni, MD, PhD

Enrollment Contacts: alsdigitalstudies@mgb.org
Lindy Feintuch, 617-724-0783
Sravan Mandepudi, 617-643-6036

Study of Longitudinal Microbiome in ALS

Enroll and participate from your home!

Full Study Name: Longitudinal Assessment of the Gut Microbiome in People with ALS

Study Length: Up to 5 years

Participants: People with ALS, asymptomatic ALS gene carriers, healthy volunteers

Biomarkers: Stool and blood samples

Purpose: To collect and analyze stool samples and observe the relationship between the gut microbiome and the progression of ALS over time. Information collected in this study will further our understanding of ALS and contribute towards the development of novel therapeutics.

Principal Investigator: James Berry, MD, MPH

Sponsor: National Institutes of Health and Brigham and Women’s Hospital

Enrollment Contacts: mgh-als-microbiome@mgb.org
Lada Filippov, 617-724-7048
Carolyn Dwyer, 617-724-7928

Study of Pison

Full Study Name: The Pison Digital Biomarker for ALS

Study Length: This study requires one in-person clinic visit at MGH, which will take around 3 hours.

Participants: People with ALS and healthy controls between the ages of 18 and 80. Participants must be able to weakly grip a handheld strength device and walk, either with or without an assistive device.

Purpose of Study: To demonstrate that Pison is capable of being used by a person living with ALS and that the Pison Digital Biomarker can be identified in extremities without clinical weakness.

Study Assessments: The study asks participants to review their medical history, medications, and demographics. Participants with ALS will also complete the ALS Functional Rating Scale-Revised (ALSFRS-R) and Rasch-built Overall ALS Disability Scale (ROADS). All participants will wear a monitoring device on each of their arms and legs. They will then complete a variety of physical assessments, including strength/grip tests, a walking test, and a reaction time test. A short neurological exam will also be conducted.

Principal Investigator: James Berry, MD, MPH

Enrollment Contacts: alsdigitalstudies@mgb.org
Sravan Mandepudi, 617-643-6036
Lindy Feintuch, 617-724-0783

Study of PREVENT ALL ALS

Full Study Name: PREVENT ALL ALS – Longitudinal Biomarker Study for Participants Who are At Risk for ALS

Study Length: up to 3 years (6 remote visits/3 yearly in-person visits)

Participants: People who are asymptomatic ALS gene carriers or have a family history of ALS

Biomarkers: Blood and optional cerebrospinal fluid collection

Purpose: To study people at risk for developing ALS and broaden our understanding of causes of underlying early disease changes. The information collected in this study may result in the development of treatments that target the earliest changes in ALS and lead to possible disease prevention.

Principal Investigator: James Berry, MD, MPH

Sponsor: National Institutes of Health and St. Joseph’s Hospital and Medical Center, Phoenix, AZ

Enrollment Contacts: mghpreventallals@mgb.org
Anika Allen, 617-724-9196
Lucy Sullivan, 617-726-1880

Read PREVENT Brochure

Study of Respiratory Comorbidity Detection Using Digital Devices

Full Study Name: Respiratory Comorbidity Detection Using Digital Devices (Empatica) Sponsor: ALS Association Study Length: 18 Months Participants: People living with ALS who qualify for breathing support and use assistive devices for mobility. We are also looking for volunteers who have not been diagnosed with ALS or have a relative with confirmed genetic ALS. Purpose of Study: We aim to improve monitoring of respiratory complications like pneumonia, pulmonary embolisms or deep vein thromboses in people living with ALS using smartwatch sensors (Empatica device). The study could help develop better detection and treatment methods for these respiratory complications related to ALS. Study Assessments: Participants will have visits every three months for a total of 7 in-person visits. At the visits, participants will undergo imaging, blood tests, ALS clinical exams, and symptom surveys. Principal Investigator: James Berry MD, MPH Enrollment Contacts: alsdigitalstudies@mgb.org Sravan Mandepudi, 617-643-6036 Lindy Feintuch, 617-724-0783

Study of Speech, Social Connectedness, and Well-Being Outcomes in ALS

Full Study Name: Speech, Social Connectedness, and Well-being Outcomes in ALS Study Length: 7 months Participants: People with ALS Purpose of Study: To understand the impact of ALS and associated speech impairments on social connectedness and quality of life. Study Assessments: The study asks each participant to use a smartphone for a few minutes a day and to complete surveys, and record your voice at two time points about 6 months apart. You will also meet with a researcher over video two times to complete surveys; and mobility, cognitive, and speech tasks. The smartphone will collect passive data for the first and last month of the study. Principal Investigator: Kathryn Connaghan, PhD Enrollment Contact: alsdigitalstudies@mgb.org Lindy Feintuch, 617-724-0783 Sravan Mandepudi, 617-643-6036

Study of Target ALS

Full Study Name: Target ALS Biomarker Study: Longitudinal Biofluids, Clinical Measures, and At-Home Measures Study Length: 16 months for ALS participants, 12 months for healthy volunteers Participants: ALS patients and healthy volunteers able to have lumbar punctures Biomarkers: Blood, spinal fluid, urine Purpose of Study: The goal of the study is to build a library of samples (blood, cerebral spinal fluid, and urine) and linked medical and genetic data. Collaborating researchers will have access to this information to advance their knowledge of ALS. Principal Investigator: James Berry, MD, MPH Sponsor: Target ALS Enrollment Contacts: targetals@mgb.org Lada Filippov, 617-724-7048 Carolyn Dwyer, 617-724-7928