Clinical Trials at the Healey & AMG Center for ALS

The HEALEY Platform Trial tests multiple regimens. Each regimen is being conducted to see if the specified investigational drug is a safe and effective treatment option for people diagnosed with ALS. 

Current Active Regimens

Regimen F: Trial of ABBV-CLS-762 (Now Enrolling)
Developed by Calico in collaboration with AbbVie, ABBV-CLS-7262 targets eIF2B, a key regulator of the integrated stress response (ISR), a pathway activated in people with ALS. In neurons exposed to cellular stressors, inhibition of the ISR by ABBV-CLS-7262 restores protein synthesis and dissolves pre-formed TDP-43 containing stress granules. This effect of ABBV-CLS-7262 is of clinical interest because TDP-43 containing stress granules are thought to lead to TDP-43 inclusions, a hallmark of ALS pathology.

Regimen G: Trial of DNL343 (Now Enrolling)
DNL343 is a novel investigational ALS therapy that targets eIF2B, a central regulator of the integrated stress response (ISR). The ISR appears to be overactive in ALS, leading to the formation of stress granules containing TDP-43. Buildup of TDP-43 is harmful and leads to neuronal degeneration. In the lab, inhibition of the ISR by DNL343 dissolves TDP-43 containing stress granules and decreases ISR biomarkers. The safety, pharmacokinetics, and pharmacodynamics of DNL343 have been characterized in both healthy participants and people with ALS, in a Phase 1 (N=47) and a Phase 1b (N=29) study, respectively, with dosing for up to 28 days. Results from both studies demonstrated that once-daily oral dosing with DNL343 was generally well tolerated and exhibited extensive Cerebrospinal Fluid (CSF) penetration. In addition, robust inhibition of biomarkers associated with the ISR pathway was observed in blood samples from study participants.

No Longer Enrolling

Regimen A: Trial of Zilucoplan 
Developed by UCB

Regimen B: Trial of Verdiperstat
Developed by Biohaven Pharmaceuticals

Regimen C: Trial of CNM-Au8
Developed by Clene Nanomedicine

Regimen D: Trial of Pridopidine
Developed by Prilenia Therapeutics

Regimen E: Trial of Trehalose (SLS-005)
Developed by Seelos Therapeutics

For participation at Massachusetts General Hospital:
Email: MGHsiteHealeyPlatform@mgh.harvard.edu
Phone: 617-643-3902

For participation at other sites, contact the Patient Navigator:
Email: HealeyALSplatform@mgh.harvard.edu
Phone: 833-425-8257

Full Trial Name: Neurodegenerative Alzheimer’s Disease and Amyotrophic Lateral Sclerosis (NADALS) Basket Proof of Concept Trial including Asymptomatic Individuals using Baricitinib

Trial Phase: Phase 1-2

Trial Length: Up to 28 weeks (Up to 7 in-person visits)

Drug to Placebo Ratio: No Placebo

Target: Type I interferon signaling

Science: Baricitinib aims to block type I interferon signaling, which is robustly active within the central nervous system of subsets of patients with Amyotrophic Lateral Sclerosis and Alzheimer’s Disease. Type 1 interferon signaling is an immune response that promotes inflammation which can lead to motor neurons dying and the progression of ALS symptoms. 

Administration: One 2 mg tablet once per day for the first 8 weeks of the trial, two 2 mg tablets once per day for the remaining 16 weeks. Tablets can be taken orally or crushed and administered through a G-tube

Purpose: In this study, the levels of baricitinib present in blood and cerebrospinal fluid (CSF) will be measured to determine safety and its effect on biomarkers related to ALS and AD. We hope these findings will help better evaluate the efficacy of baricitinib for the treatment of ALS. 

Principal Investigator: Doreen Ho, MD

Sponsor: Mark Albers, MD, PhD

Enrollment Contacts:

Kylie Graves, klgraves@mgh.harvard.edu, or 617-643-7912

Chloe Noll, cnoll@mgh.harvard.edu,or 617-724-7113

Full Trial Name: 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
Trial Phase: 1
Trial Length: 6-7 months (13 in-person visits)
Drug to Placebo Ratio: 2:1 or 3:1, open label extension
Target: ATXN2 protein

Science:  BIIB105 is an antisense oligonucleotide (ASO) medication that may reduce the amount of ATXN2 protein. By decreasing ATXN2, this may prevent the accumulation of TDP-43 protein, which is responsible for the death of motor neurons.

Administration: Lumbar punctures (needle inserted into spinal fluid in the lower spine to administer dose)

Purpose: To learn about the safety and tolerability of BIIB105 in adults with a diagnosis of Amyotrophic Lateral Sclerosis (ALS) and to look at the level and action of the study drug in the body and what happens to this level over time.

Principal Investigator: . Suma Babu, MBBS, MPH
Sponsor: Biogen MA, Inc.

Enrollment Contacts:
Erica Scirocco, escirocco@mgh.harvard.edu, or 617-726-1363
Munaf Hatem, mhatem@mgh.harvard.edu, or 617-643-3530

Full Trial Name: An open-label, adaptive design study in patients with ALS to characterize safety, tolerability and brain microglia response, as measured by TSPO binding, following multiple doses of BLZ945 using positron emission tomography (PET) with radioligand [11C]-PBR28

Trial Phase: 2

Trial Length: 6 months

Drug to Placebo Ratio: Open label (no placebo)

Target: Inhibitor of CSF-1R

Science: In people with ALS, immune cells in the brain called microglia are activated and cause neuroinflammation. The goal of this study is to reduce neuroinflammation through treatment of BLZ945. This will be evaluated using PBR28 PET imaging to measure microglial activation, as well as through collection of biomarkers of neuroinflammation and disease activity in participants with ALS.

Administration: Oral pill taken once per week or for the first four days of a two-week period

Purpose: To learn about the safety and tolerability of BLZ945 in adults with a diagnosis of Amyotrophic Lateral Sclerosis (ALS) and to help select the most appropriate doses for the planning of future research in patients with ALS.

Principal Investigator: Suma Babu, MD, MPH

Recruiting: 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

Sponsor: Ionis Pharmaceuticals

Full Trial Name: A Phase 1-3 Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION363 in Amyotrophic Lateral Sclerosis Patients with Fused in Sarcoma Mutations (FUS-ALS)

Trial Phase: 1-3

Trial Length: Up to 3 years and 11 months (up to 20 in-person visits)

Participants: People with FUS ALS

Drug to Placebo Ratio: 2:1 for 14 months, open label extension (OLE) for 20 months

Target: FUS RNA

Science: ION363 is an investigational antisense medicine targeting the FUS gene to reduce production of the FUS protein. There is evidence that mutations in the FUS gene can lead to rapid, progressive loss of motor neurons in patients with FUS-ALS, so this drug may reduce or prevent disease progression in FUS-ALS patients.

Administration: Lumbar puncture (needle inserted into spinal fluid in the lower spine to administer dose)

Purpose: To evaluate the efficacy of the study drug in functioning and survival in ALS patients with FUS mutations.

Full Trial Name: Phase I Trial of Autologous Hybrid TREG/Th2 Cell Therapy (RAPA-501) for Amyotrophic Lateral Sclerosis
Trial Phase: 1
Trial Length: Up to 1 year (10-30 in-person visits)
Drug to Placebo Ratio: Open Label (no placebo)
Target: T-cells

Science: In people with ALS, the body’s immune system becomes imbalanced and appears to hasten the loss of motor neurons in the brain and spinal cord. Regulatory T-cells help reduce inflammation and could lead to a more balanced immune system in people with ALS. The goal of this study is to reduce neuroinflammation, potentially slowing ALS progression, using specially prepared regulatory T-cells, called RAPA-501 cells. RAPA-501 cells are created through a series of steps by first taking the participant’s own blood though a specialized IV (apheresis), then isolating regulatory T-cells from the blood. Next, these regulatory T-cells are grown under special conditions in a petri dish, becoming RAPA-501 cells. The RAPA-501 cells are then returned to the participant through an intravenous infusion. Prior to the IV infusion of RAPA-501 cells, a low dose of chemotherapy is given to reduce the body’s immune response and potentially heighten the effects of the RAPA-501 cells.

Administration:

(1) Apheresis (blood separation) to collect T-cells

(2) Intravenous (IV) infusion of low-dose chemotherapy drugs (Cyclophosphamide and Pentostatin)

(3) Intravenous (IV) infusion of the specialized RAPA-501 cells

Purpose: The purpose of this study is to find out if RAPA-501 cell therapy is safe in people living with ALS. Two doses of RAPA-501 cells will be investigated for safety.

Principal Investigator: Dr. James Berry
Sponsor: Rapa Therapeutics, LLC
Enrollment Contacts: 
Jacqueline Topping, 617-643-6036 or jtopping@mgh.harvard.edu
Chloe Noll, cnoll@mgh.harvard.edu, or 617-724-7113

Sponsor: Sanofi US Services Inc

Full Trial Name: A Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of SAR443820 in adult participants with amyotrophic lateral sclerosis (ALS), followed by an open-label extension

Trial Phase: 2

Trial Length: 108 weeks

Drug to Placebo: 2:1, open label extension (OLE) for last 82 weeks

Target: RIPK1 receptor

Science: SAR44380 inhibits a receptor in your nervous system called RIPK1. When RIPK1 is activated, it results in inflammation and damage to your cells. Because SAR443820 works by blocking RIPK1, it may help reduce inflammation and damage to cells in your nervous system and interfere with the pathway causing ALS.

Administration: Oral pill taken twice daily

Purpose: To learn about the safety and efficacy of SAR443820 in adults with a diagnosis of Amyotrophic Lateral Sclerosis (ALS) and to look at the level and action of the study drug in the body and what happens to this level over time.

Principal Investigator: Dr. Doreen Ho

Enrollment Contacts: 
Amrita Iyer, 617-643-9550, aiyer2@mgh.harvard.edu
Chrysthie Moline, cmoline@bwh.harvard.edu, or 617-643-2499

Full Trial Name: ALS Sample Repository 

Study Length: 1 in-person visit  

Participants: People with ALS, PLS, other MND, healthy volunteers

Biomarkers: Blood, spinal fluid, and/or urine samples 

Purpose: To answer questions and support research related to cause, prevention, treatment, and hereditability of ALS. 

Principal Investigator: Dr. James D. Berry, MD, MPH 

Sponsor: Hollister Lindley Fund

Enrollment Contact: 
Ethan Riddell, eriddell@mgh.harvard.edu, 617-643-4803
Chrysthie Moline, cmoline@bwh.harvard.edu, 617-643-2499

+Amyotrophic Lateral Sclerosis
+Asymptomatic ALS Gene Carriers
+Healthy Volunteers

Full Trial Name: A Longitudinal Analysis of Biomarkers in Patients with ALS 

Trial Length: 2 ½ years (7 in-person visits) 

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

Biomarkers: Blood, urine, and cerebrospinal fluid 

Purpose: To test potential biomarkers over time, which can be used to further uncover ALS pathophysiology, discover disease biomarkers, and identify new therapeutic targets. The biomarkers may help diagnose ALS sooner, monitor ALS progression, and teach us about potential causes and treatments for ALS. The samples we collect will be used to compare and analyze changes in immune cells and other changes in plasma and gene expression.

Principal Investigator: James Berry, MD, MPH 

Sponsor: Holy Cross Hospital, Inc.

Enrollment Contact: Chloe Noll, 617-724-7113, cnoll@mgh.harvard.edu  or Jacqueline Topping, 617-643-6036 or jtopping@mgh.harvard.edu

+Amyotrophic Lateral Sclerosis
+Asymptomatic ALS Gene Carriers
+Healthy Volunteers

Enroll and participate from your home!

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

Study Length: 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 Contact:
Jacqueline Topping, 617-643-6036 or jtopping@mgh.harvard.edu
Ethan Riddell, eriddell@mgh.harvard.edu, 617-643-4803

Recruiting: Patients with Amyotrophic Lateral Sclerosis, Primary Lateral Sclerosis, Hereditary Spastic Paraplegia or Frontotemporal Dementia
Healthy Volunteers Who Are Known Carriers of ALS Gene

Full Trial Name: Glial Activation Measured by PBR28-PET in People with Neurodegenerative Diseases
The purpose of the study is to learn more about inflammation in the brains of people with Motor Neuron Disease (MND) using combined Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). Our study will examine whether particular cells, called microglia, are hyperactive in the nervous system of people with MND, such as those individuals with ALS.

Study participation involves two visits to MGH over a maximum of three months. Participants must be between the ages of 18 and 80, be medically safe to undergo an MRI scan and be able to safely lie flat for at least 90 minutes. Additionally, participants cannot be taking any immunosuppressive medications or have a diaphragm pacing system and cannot have a diagnosis of Parkinson’s disease, Alzheimer’s disease, unstable psychiatric disease, or renal failure. All participants will be reimbursed for parking and receive compensation of $150 upon completion of each MR-PET scan. There will be additional compensation of $100 for each lumbar puncture completed by individuals with MND.

Principal Investigator: Suma Babu, MD, MPH

Sponsors: Neurodegenerative Disease Pilot Study Grant, K23 NS 083715, Evan and Arlene Yegelwel Endowed Fund for Primary Lateral Sclerosis Research and Care, PET Imaging of inflammation and epigenetics in ALS (ALS ONE), Muscular Dystrophy Association, Sundry

Enrollment Contacts:
Henry Rutherford, hrutherford@bwh.harvard.edu or 617-643-6252
Jingqi Zhu, jzhu34@mgh.harvard.edu, or 617-643-2522

Full Trial Name: Feasibility and Sensitivity of a Symptom Monitoring Application in Real Time (SMART) for ALS 

Trial Length: 12 months 

Participants: People with ALS and healthy volunteers 

Purpose of Study: To determine the usefulness of a smartphone app in collecting research data and to learn more about disease progression. 

Study Assessments: The study asks each participant to use the smartphone application for a few minutes every day by answering a questionnaire/survey, recording your voice and/or performing an on-screen exercise. The study requires participants to download and use the smartphone application using their smartphone device running iOS 8 or higher, or Android 4.1 or higher. 

Principal Investigator: James Berry MD, MPH 
Sponsor: ALS Finding a Cure 
Enrollment Contacts:
 Amrita Iyer, aiyer2@mgh.harvard.edu, 617-643-9550 

Full Trial Name: A Phase 2a Trial to Evaluate the Safety, Tolerability, and Biological Activity of LAM-002A (apilimod dimesylate capsules) in C9ORF72-Associated ALS

Trial Phase: 2a

The aim of this Phase 2 research study is to find out if LAM-002A is a safe treatment option for patients with C9ORF72-associated ALS (C9ALS). During the study, participants will receive the LAM-002A drug orally in pill form. This is an open label extension trial, meaning that for the first 12 weeks, some participants will receive a placebo (which looks like the study drug, but has no active ingredients) instead of LAM-002A. Following the completion of weeks 1-12, all participants will be eligible to receive LAM-002A for the next 12 weeks of the trial. Participation in this study will involve blood draws, lumbar punctures, and several clinical measures of ALS, as research staff seek to understand how LAM-002A is processed by the body and if it impacts ALS progression. Our team is looking for patients with C9ALS and a slow vital capacity of ≥50% who are willing to complete 10 study visits and several phone calls over 28 weeks. Please reach out to the enrollment contact listed below: 

Principal Investigator: Suma Babu, MD, MPH
Sponsor: AI Therapeutics, Inc.
Enrollment Contact: Shea Golden, 617-724-3268 or sgolden3@mgh.harvard.edu
Allison Carey, 617-726-1559 or abcarey@mgh.harvard.edu

Full Trial Name: A Phase 2a Study of TPN-101 in Patients with C9ORF72 ALS/FTD (Amyotrophic Lateral Sclerosis and/or Frontotemporal Dementia) 

Trial Phase: 2 

Trial Length: 13-14 months (13 in-person visits) 

Participants: People with C9 ALS and/or FTD 

Drug to Placebo: 3:2 for 24 weeks, open label extension (OLE) for 24 weeks 

Target: Retrotransposon hL1 

Science: TPN-101 works to prevent hL1 expression, since hL1 may cause further ALS progression. HL1 is shown to be overexpressed in C9ALS causing DNA damage and neuroinflammation. TPN-101 may suppress hL1 expression to prevent progression. Ï

Administration: Gel capsule taken orally 

Purpose: To assess the safety and tolerability of the drug TPN-101 in patients with C9orf72 ALS and/or FTD. This study will also measure the levels and efficacy of the drug in your body over time. 

Principal Investigator: Dr. James D. Berry, MD, MPH 

Sponsor: Transposon Therapeutics, Inc. 

Enrollment Contact:
Jacqueline Topping, jtopping@mgh.harvard.edu , 617-643-6036

Full Trial Name: A Phase 1, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB067 Administered to Adult Subjects with Amyotrophic Lateral Sclerosis
Trial Phase: 3

We are doing this research study to find out about the safety and tolerability of the study drug BIIB067. The study is funded by Biogen MA Inc. This study is recruiting patients with SOD1-Amyotrophic Lateral Sclerosis (SOD1-ALS) with a forced vital capacity greater than or equal to 50% of predicted value. Participation in the study will last for approximately 31 weeks and will include an overnight stay at MGH in addition to in person visits. The study team can provide additional information on the number of required visits during your initial visit. There are additional inclusion/exclusion criteria that the study team will review with you in more detail.

Principal Investigator: Suma Babu, MD, MPH
Sponsor: Biogen MA Inc.
Enrollment Contact:
Shea Golden, 617-724-3268, sgolden3@mgh.harvard.edu
Munaf Hatem, mhatem@mgh.harvard.edu, 617-643-3530