Table 1.
List of clinical trials carried out on ALS using different omics approaches.
| Amyotrophic Lateral Sclerosis | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Clinical Trials Identifier | Date | Phase | Status | Treatment | Approach | Title | State | Phase | ||
| Start | Completion | Name | Drug | |||||||
| NCT01041222 | January 2010 | January 2012 | Completed | fALS diagnosis: SOD1 gene mutation carries | ISIS 333611 | ASO designed to inhibit SOD1 expression | Genomics | A Phase 1, Double-Blind, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of ISIS 333,611 Administered Intrathecally to Patients with Familial Amyotrophic Lateral Sclerosis Due to Superoxide Dismutase 1 Gene Mutations | United States | I |
| NCT00706147 | January 2009 | December 2014 | Completed | SOD1 genetic mutation | Arimoclomol | HSP response inductor | Genomics | Phase II/III Randomized, Placebo-Controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis (ALS). | United States | II-III |
| NCT04494256 | 28 September 2020 | Recruiting | Genetic diagnosis (SOD1, FUS, ATXN2) | BIIB105 | ASO is designed to bind ATXN2 mRNA and mediate its degradation | Genomics | 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. | United States | I | |
| NCT04632225 | 9 February 2021 | Active, not recruiting | ALS diagnosis according to the El Escorial Criteria | Engensis | Gene therapy using plasmid to deliver the HGF gene directly to nerve cells | Transcriptomics | A Phase 2a, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety of Engensis in Participants with Amyotrophic Lateral Sclerosis | United States | II | |
| NCT03359538 | 19 September 2017 | Active, not recruiting | ALS diagnosis according to the El Escorial Criteria | Rapamycin—Sirolimus | Immunomodulatory effects and improves protein degradation | Transcriptomics | Rapamycin (Sirolimus) Treatment for Amyotrophic Lateral Sclerosis | Italy | II | |
| NCT00875446 | 13 May 2009 | 9 September 2011 | Completed | ALS diagnosis according to the Gold Coast Criteria |
GSK1223249- Ozanezumab |
Monoclonal antibody targeting NOGO-A protein | Transcriptomics and metabolomics | A Single and Repeat Dose Escalation Study of the Safety, Pharmacokinetics and Pharmacodynamics of GSK1223249 in ALS Patients | United States | I |
| NCT03456882 | 18 November 2016 | 23 November 2020 | Completed | ALS diagnosis according to the El Escorial Criteria | RNS60 | Saline solution with charged oxygenated nanobubbles | Metabolomics and transcriptomics | The Effect of RNS60 on ALS Biomarkers. | Italy | II |
| NCT01854294 | August 2013 | April 2014 | Completed | ALS diagnosis according to the El Escorial Criteria | GM604 | Peptide | Transcriptomics | GM604 Phase 2A Randomized Double-blind Placebo Controlled Pilot Trial in Amyotrophic Lateral Disease (ALS) | United States | II |
| NCT03800524 | 22 February 2019 | Recruiting | ALS diagnosis according to the El Escorial Criteria | Tauroursodeoxycholic | Antiapoptotic and ER stress response damping effects | Transcriptomics | Safety and Efficacy of Tauroursodeoxycholic (TUDCA) as add-on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis (ALS) | Belgium, France and others | III | |
| NCT04505358 | 30 December 2021 | Not yet recruiting | ALS diagnosis according to the El Escorial Criteria | PU-AD— Icapamespib |
Brain permeable Hsp90 protein inhibitor | Genomics and transcriptome | A Randomized, Double-blind, Placebo-controlled Pilot Study to Evaluate the Biological Activity, Safety, and Pharmacokinetics of PU-AD in Subjects with Amyotrophic Lateral Sclerosis (ALS) | II | ||
| NCT03693781 | 10 April 2019 | Active, not recruiting | ALS diagnosis according to the El Escorial Criteria | Colchicine | Transcriptomics | Colchicine for Amyotrophic Lateral Sclerosis: A Phase II, Randomized, Double Blind, Placebo Controlled, Multicenter Clinical Trial | Italy | II | ||
| NCT01884571 | October 2013 | January 2016 | Completed | ALS diagnosis according to the El Escorial Criteria | Basiliximab, Methylprednisolone, Prednisone, Tacrolimus, Mycophenolate mofetil | Immunosuppression treatment | Transcriptomics | A Novel Immunosuppression Intervention for the Treatment of Amyotrophic Lateral Sclerosis (ALS) | United States | II |
| NCT02525471 | October 2015 | 21 June 2017 | Completed | ALS diagnosis according to the El Escorial Criteria | RNS60 | Saline solution with charged oxygenated nanobubbles | Transcriptomics | A Pilot Study of RNS60 in Amyotrophic Lateral Sclerosis (ALS) | United States | I |
| NCT02469896 | November 2015 | 11 July 2018 | Completed | ALS diagnosis according to the El Escorial Criteria | Tocilizumab | ASO designed to inhibit interleukin 6 (IL-6) |
Transcriptomics | A Phase 2 Randomized, Placebo Controlled Trial of Tocilizumab in ALS Subjects | United States | II |
| NCT05193994 | 18 January 2022 | Not yet recruiting | ALS diagnosis according to the Gold Coast Criteria | Triumeq | Combined treatment of: dolutegravir, abacavir, lamivudine | Genomics and transcriptomics | Randomised Double-Blind Placebo-Controlled Phase 3 Trial of Triumeq in Amyotrophic Lateral Sclerosis | Australia | III | |
| NCT04788745 | 29 June 2021 | Recruiting | ALS diagnosis according to the El Escorial Criteria | Trimetazidine Dihydrochloride | Transcriptomics | Targeting Metabolic Flexibility in ALS (MetFlex); Safety and Tolerability of Trimetazidine for the Treatment of ALS | Australia, United Kindom and others | II | ||
| NCT04840823 | 26 March 2021 | Recruiting | ALS diagnosis according to the El Escorial Criteria | Enoxacin | Quinolone/fluoroquinolone antibiotic | Transcriptomics | A Randomized, Double-blind, Parallel Group, Single Centre, Phase 1b/2 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Three Orally Administered Doses of Enoxacin (200 mg Twice Daily, 400 mg Twice Daily and 600 mg Twice Daily) in Adults with Amyotrophic Lateral Sclerosis | Canada | I-II | |
| NCT02437110 | 1 April 2019 | Recruiting | ALS diagnosis according to the El Escorial Criteria | Darunavir, Ritonavir, Dolutegravir, Tenofovir alafenamide (TAF) | Darunavir and Ritonavir = protease inhibitor; Dolutegravir = integrase inhibitor; TAF = nucleoside reverse transcriptase inhibitor | Transcriptomics | HERV-K Suppression Using Antiretroviral Therapy in Volunteers with Amyotrophic Lateral Sclerosis (ALS) | United States | I | |
| NCT04066244 | 30 December 2019 | Recruiting | ALS diagnosis according to the El Escorial Criteria | BLZ945 | CSF-1 Inhibitor | Genomics Metabolomics and transcriptomics | An Open-label, Adaptive Design Study in Patients with Amyotrophic Lateral Sclerosis (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 the Radioligand [11C]-PBR28 | United States | II | |
| NCT03626012 | 10 September 2018 | 17 November 2021 | Completed |
C9Orf72 genetic mutation |
BIIB078 | ASO designed to target C9Orf72 mRNA | Genomics and metabolomics | 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 | United States, Belgium and others | I |
| NCT04288856 | 28 April 2020 | Active, not recruiting |
C9Orf72 genetic mutation |
BIIB078 | ASO designed to target C9Orf72 mRNA | Genomics and metabolomics | An Extension Study to Assess the Long-Term Safety, Tolerability, Pharmacokinetics, and Effect on Disease Progression of BIIB078 Administered to Previously Treated Adults with C9ORF72-Associated Amyotrophic Lateral Sclerosis | United States | I | |
| NCT05163886 | 23 December 2021 | Recruiting |
C9Orf72 genetic mutation |
LAM-002A | PIKfyve kinase inhibitor that activates the transcription factor EB (TFEB) | Genomics and transcriptome | A Phase IIa Trial to Evaluate the Safety, Tolerability, and Biological Activity of LAM-002A (Apilimod Dimesylate Capsules) in C9ORF72-Associated Amyotrophic Lateral Sclerosis | United States | II | |
| NCT05053035 | 2 September 2021 | Recruiting |
C9Orf72 genetic mutation |
LAM-002A | PIKfyve kinase inhibitor that activates the transcription factor EB (TFEB) | Genomics and transcriptome | A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AL001 in C9orf72-Associated Amyotrophic Lateral Sclerosis | United States | II | |
| NCT04993755 | 1 October 2021 | Recruiting |
C9Orf72 genetic mutation |
TPN-101, censavudine |
Inhibitor of the reverse transcriptase enzyme | Genomics and metabolomics | A Phase 2a Study of TPN-101 in Patients with Amyotrophic Lateral Sclerosis (ALS) and/or Frontotemporal Dementia (FTD) Associated with Hexanucleotide Repeat Expansion in the C9Orf72 Gene (C9ORF72 ALS/FTD) | United States | II | |
| NCT04931862 | 28 June 2021 | Recruiting |
C9Orf72 genetic mutation |
WVE-004 | ASO is designed to mediate the degradation of C9ORF72 mRNAs | Genomics | A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-004 Administered Intrathecally to Patients with C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD) | Australia | I-II | |
| NCT02623699 | 20 January 2016 | 16 July 2021 | Completed | SOD1 genetic mutation | BIIB067—Tofersen | ASO designed to degrade SOD1 mRNA to prevent protein synthesis and reduce levels of harmful proteins. | Genomics and metabolomics | A Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB067 Administered to Adult Subjects with Amyotrophic Lateral Sclerosis and Confirmed Superoxide Dismutase 1 Mutation | United States | III |
| NCT03070119 | 8 March 2017 | Active, not recruiting | SOD1 genetic mutation | BIIB067—Tofersen | ASO designed to degrade SOD1 mRNA to prevent protein synthesis and reduce levels of harmful proteins. | Genomics | An Extension Study to Assess the Long-Term Safety, Tolerability, Pharmacokinetics, and Effect on Disease Progression of BIIB067 Administered to Previously Treated Adults with Amyotrophic Lateral Sclerosis Caused by Superoxide Dismutase 1 Mutation | United States | III | |
| NCT04856982 | 17 May 2021 | Recruiting | SOD1 genetic mutation | BIIB067—Tofersen | ASO designed to degrade SOD1 mRNA to prevent protein synthesis and reduce levels of harmful proteins. | Genomics and metabolomics | A Phase 3 Randomized, Placebo-Controlled Trial with a Longitudinal Natural History Run-In and Open-Label Extension to Evaluate BIIB067 Initiated in Clinically Presymptomatic Adults with a Confirmed Superoxide Dismutase 1 Mutation | United States | III | |
| NCT01083667 | November 2009 | December 2014 | Completed | SOD1 genetic mutation | Pyrimethamine – Daraprim |
Genomics and metabolomics | Phase I/II Study of SOD1 Inhibition by Pyrimethamine in Familial ALS | United States, Germany and others | I-II | |
| NCT04768972 | 14 June 2021 | Recruiting |
FUS genetic mutation |
ION363—JaciFUS en | ASO designed to reduce the production of a mutated neurotoxic form of the FUS protein | Genomics and metabolomics | A Phase 1–3 Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION363 in Amyotrophic Lateral Sclerosis Patients with FUS ed in Sarcoma Mutations (FUS -ALS) | United States | III | |
| NCT03707795 | 21 August 2017 | 10 January 2019 | Completed |
FUS genetic mutation and fALS diagnosis |
Betamethasone | Corticosteroid, reducing inflammation and changing the body’s immune response | Genomics and metabolomics | Treatment of FUS -Related ALS With Betamethasone—The TRANSLATE Study | United States | Early I |
| NCT05189106 | 1 February 2022 | Not yet recruiting |
ALS diagnosis according to the El Escorial Criteria | Baricitinib— Olumiant |
Immunosuppressant—JAK inhibitors | Genomics, proteomics and metabolomics |
Neurodegenerative Alzheimer’s Disease and Amyotrophic Lateral Sclerosis (NADALS) Basket Proof of Concept Trial Including Asymptomatic Individuals Using Baricitinib | United States | I-II | |
| NCT04220021 | 10 January 2020 | Recruiting |
C9Orf72 genetic mutation |
Metformin | Genomics and metabolomics | A Single-Center, Open Label Study to Assess the Safety and Tolerability of Metformin in Subjects with C9orf72 Amyotrophic Lateral Sclerosis Over 24 Weeks of Treatment | United States | II | ||
| NCT02590276 | 8 October 2015 | 27 October 2020 | Completed |
C9Orf72 genetic mutation |
Genomics, Metabolomics and transcriptomics | Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis | France | Not Applicable | ||
| NCT03984708 | 27 January 2020 | Recruiting | ALS diagnosis according to the El Escorial Criteria | Metabolomics, lipidpomics and transcriptomics | New Therapeutic Strategy in ALS Based on Metabolic Status and Associated Metabolic Pathways. | France | Not Applicable | |||
| NCT01984957 | January 2013 | January 2015 | Completed | ALS diagnosis according to the El Escorial Criteria | Transcriptomics | Differential Study of Muscle Transcriptome in Patients with Neuromuscular Disease and Control Subjects | France | Not Applicable | ||
| NCT02670226 | 29 March 2016 | 9 December 2019 | Completed | ALS diagnosis according to the El Escorial Criteria | Metabolomics and transcriptomics | Metabolomics and Transcriptomics Approaches to Identify Muscular Biomarkers in Amyotrophic Lateral Sclerosis | France | Not Applicable | ||
| NCT03851302 | 28 October 2019 | Recruiting | ALS diagnosis according to the El Escorial Criteria | Transcriptomics | Effects of Remote Ischemic Conditioning on Hand Use in Individuals with Spinal Cord Injury and Amyotrophic Lateral Sclerosis: A Preliminary Study | United States | Not Applicable | |||
| NCT03618966 | 1 November 2014 | 1 May 2016 | Completed | ALS diagnosis according to the El Escorial Criteria | Transcriptomics | Neuromuscular Magnetic Stimulation Counteracts Muscle Decline in ALS Patients | II | |||
| NCT03367650 | 13 May 2014 | Recruiting | ALS diagnosis according to the El Escorial Criteria | Genomics | Epidemiology and Genetics of the Amyotrophic Lateral Sclerosis in the French West Indies | France | Not Applicable | |||
| NCT03573466 | 10 April 2019 | Active, not recruiting |
SOD1- C9Orf72 genetic mutation |
Genomics | Presymptomatic Neuromuscular Junction Defects and Compensatory Mechanisms in Amyotrophic Lateral Sclerosis (ALS) | France | Not Applicable | |||
The search for clinical trials in the ClinicalTrials.gov database was carried out using “Amyotrophic Lateral Sclerosis” and “mutation”, “mutational”, “gene expression”, “genotype”, “gene”, “transcriptome”, “transcriptomics”, “C9Orf72”, “SOD1”, “FUS”, “TARDBP”, “DNA”, “RNA”, “sequencing” as keywords. The names of genes are in italics.