Tofersen for ALS
(ATLAS Trial)
Recruiting in Palo Alto (17 mi)
+66 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Biogen
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing a medication called tofersen in adults who have a genetic mutation that can lead to ALS, a serious nerve disease. These individuals show early signs of nerve damage. Tofersen works by lowering harmful proteins in the body to protect nerves and potentially delay or prevent the disease.
Do I need to stop my current medications to join the trial?
Yes, you may need to stop certain medications. If you are taking riluzole, edaravone, or sodium phenylbutyrate/taurursodiol, you must discontinue them for at least 5 half-lives before screening. You also cannot use off-label ALS treatments or other investigational drugs within a specified period before the study.
What data supports the idea that Tofersen for ALS is an effective drug?
The available research shows that Tofersen, also known as Qalsody, is effective for treating ALS in adults with a specific genetic mutation. It was approved in the USA for this purpose in April 2023. Tofersen works by targeting and reducing a harmful protein linked to ALS. Unlike other treatments like riluzole and edaravone, which only help with symptoms, Tofersen addresses a key cause of the disease. This makes it the first gene therapy for ALS, offering a new way to manage the condition.
12345What safety data exists for Tofersen in ALS treatment?
Tofersen, also known as Qalsody, has been studied in various clinical trials, including a phase III study (VALOR) and a phase 1-2 trial, for its safety and efficacy in treating ALS associated with SOD1 mutations. It was approved by the US FDA on April 25, 2023, for adults with SOD1 ALS, indicating that safety data was sufficient for regulatory approval. Additionally, it has been used in an expanded access program, suggesting ongoing evaluation of its safety profile in clinical practice.
12346Eligibility Criteria
This trial is for adults who carry a specific gene mutation (SOD1) linked to ALS but don't yet show symptoms. They must have low neurofilament levels and not be on certain ALS treatments or other clinical trials. People with severe mental health issues, active infections like HIV or hepatitis, or those at risk of bleeding complications can't participate.Inclusion Criteria
I do not show any symptoms of ALS.
I do not show any symptoms of ALS.
My ALS is due to a specific SOD1 mutation confirmed by experts.
+2 more
Exclusion Criteria
I have stopped my ALS medications for enough time before screening.
History of systemic hypersensitivity reaction to tofersen, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study
I haven't taken any experimental drugs or treatments recently.
+10 more
Participant Groups
The study tests Tofersen's effectiveness in delaying the onset of ALS symptoms in people with an SOD1 mutation. Participants will either receive Tofersen or a placebo without knowing which one they're getting to compare outcomes fairly.
4Treatment groups
Experimental Treatment
Active Control
Group I: Part D: Open-Label TreatmentExperimental Treatment1 Intervention
Participants from Part A who develop clinically manifest ALS prior to randomization in Part B may be eligible to participate in Part D. During Part D, participants will receive tofersen100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years.
Group II: Part C: Open-Label ExtensionExperimental Treatment2 Interventions
Participants from Part B who develop clinically manifest ALS may be eligible to participate in Part C. During Part C, participants who received placebo in Part B will receive tofersen 100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter up to the final maintenance dost visit. Participants who received tofersen during Part B will receive tofersen 100 mg on Days 1, 29, and every 28 days thereafter up to the final maintenance dost visit, with a dose of placebo on Day 15 to maintain the study blind. The combined duration of Part B and Part C is up to approximately 5.6 years.
Group III: Part B: Randomized, Double-Blind, Placebo-ControlledExperimental Treatment2 Interventions
Participants from Part A who meet the protocol-defined NfL threshold and remain presymptomatic may be eligible to participate in Part B. During Part B, participants will receive tofersen 100 milligram (mg) or placebo via intrathecal (IT) injection on Days 1, 15, 29, and every 28 days thereafter for up to approximately 5.6 years.
Group IV: Part A: Natural History Run-inActive Control1 Intervention
Participants enrolled in Part A will undergo blood draws approximately once every 28 days to assess neurofilament light chain (NfL) levels.
BIIB067 (Tofersen) is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Qalsody for:
- Amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene
🇪🇺 Approved in European Union as Qalsody for:
- Amyotrophic lateral sclerosis (ALS) caused by a defective superoxide dismutase 1 (SOD1) protein
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Columbia University Medical CenterNew York, NY
Montreal Neurological Hospital and InstituteMontréal, Canada
Research SiteCalgary, Canada
Research SiteMontréal, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
BiogenLead Sponsor
References
Tofersen: First Approval. [2023]Tofersen (Qalsody™) is an antisense oligonucleotide being developed by Biogen for the treatment of amyotrophic lateral sclerosis (ALS). On 25 April 2023, tofersen was approved in the USA for the treatment of ALS in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This article summarizes the milestones in the development of tofersen leading to this first approval for ALS.
Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. [2022]Label="BACKGROUND">The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated with mutations in SOD1 (SOD1 ALS).
Breaking barriers with tofersen: Enhancing therapeutic opportunities in amyotrophic lateral sclerosis. [2023]Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects adults, characterized by muscle weakness resulting from the specific death of motor neurons in the spinal cord and brain. The pathogenesis of ALS is associated with the accumulation of mutant superoxide dismutase 1 (SOD1) proteins and neurofilaments in motor neurons, highlighting the critical need for disease-modifying treatments. Current therapies, such as riluzole and edaravone, provide only symptomatic relief. Recently, tofersen gained approval from the US FDA under the brand name Qalsody as the first and only gene therapy for ALS, addressing a significant pathological aspect of the disease.
Neurofilament light-chain response during therapy with antisense oligonucleotide tofersen in SOD1-related ALS: Treatment experience in clinical practice. [2023]In amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1-ALS), the antisense oligonucleotide tofersen had been investigated in a phase III study (VALOR) and subsequently introduced in an expanded access program. In this study we assess neurofilament light chain (NfL) before and during tofersen treatment.
Design of a Randomized, Placebo-Controlled, Phase 3 Trial of Tofersen Initiated in Clinically Presymptomatic SOD1 Variant Carriers: the ATLAS Study. [2022]Despite extensive research, amyotrophic lateral sclerosis (ALS) remains a progressive and invariably fatal neurodegenerative disease. Limited knowledge of the underlying causes of ALS has made it difficult to target upstream biological mechanisms of disease, and therapeutic interventions are usually administered relatively late in the course of disease. Genetic forms of ALS offer a unique opportunity for therapeutic development, as genetic associations may reveal potential insights into disease etiology. Genetic ALS may also be amenable to investigating earlier intervention given the possibility of identifying clinically presymptomatic, at-risk individuals with causative genetic variants. There is increasing evidence for a presymptomatic phase of ALS, with biomarker data from the Pre-Symptomatic Familial ALS (Pre-fALS) study showing that an elevation in blood neurofilament light chain (NfL) precedes phenoconversion to clinically manifest disease. Tofersen is an investigational antisense oligonucleotide designed to reduce synthesis of superoxide dismutase 1 (SOD1) protein through degradation of SOD1 mRNA. Informed by Pre-fALS and the tofersen clinical development program, the ATLAS study (NCT04856982) is designed to evaluate the impact of initiating tofersen in presymptomatic carriers of SOD1 variants associated with high or complete penetrance and rapid disease progression who also have biomarker evidence of disease activity (elevated plasma NfL). The ATLAS study will investigate whether tofersen can delay the emergence of clinically manifest ALS. To our knowledge, ATLAS is the first interventional trial in presymptomatic ALS and has the potential to yield important insights into the design and conduct of presymptomatic trials, identification, and monitoring of at-risk individuals, and future treatment paradigms in ALS.
Phase 1-2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. [2022]Label="BACKGROUND">Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to SOD1 mutations.
Characterization of the novel HLA-B*07:385 allele by next-generation sequencing. [2021]B*07:385 differs from B*07:02:01:01 by one nucleotide substitution at position 660 in exon 4.
A novel DRB3 allele (DRB3*0208), a new allelic variant of DRB1*1502 (DRB1*15023) and two new DQB1 (DQB1*03012 and DQB1*0614) alleles. [2019]Four novel HLA Class II alleles were identified using CANTYPE reverse hybridization assay. The initial unusual SSO hybridization patterns were confirmed by cloning and sequencing analysis. DRB3*0208 allele is identical to DRB3*0202 except for three nucleotide substitutions (GAT-->AGC) changing codon 57 from Asp to Ser. This polymorphism has so far been undetected in DRB3 alleles. DRB1*15023 differs from DRB1*15021 by a single silent nucleotide substitution (AAC-->AAT, both encoding for Asn) at codon 33. This polymorphism has not, until now, been identified in DRB alleles. Compared with DQB1*03011, the novel DQB1*03012 contains a single silent nucleotide substitution (GCA-->GCG, both encoding for Ala) at codon 38. Finally, DQB1*0614 allele is identical to DQB1*0603 except for a single nucleotide substitution (TAC-->TTC), changing codon 9 from Tyr to Phe. Polymorphisms observed here in the DQB1*03012 and DQB1*0614 alleles are present in several of the known DQB1 alleles. DRB3*0208, DQB1*03012 and DQB1*0614 may have arisen from gene conversion, but the DRB1*15023 most likely was generated by a point mutation event. DQB1*0614 was detected in three related subjects, while each of the other three new alleles has only been detected once.
Characterization of the novel HLA-C*06:283 allele by next-generation sequencing. [2021]C*06:283 differs from C*06:02:01:01 by one nucleotide substitution at position 764 in exon 4.
A Novel c.796 A>C Mutation in the ABO*B.01 Allele Responsible for CisAB Phenotype. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Individuals with the CisAB phenotype are rare in the Chinese population. In the present study, we investigated the sequence of the ABO gene and family members of a newborn suspected to have the CisAB phenotype.
[Study of the molecular basis for an individual with Bel variant due to deletion of B glycosyltransferase gene]. [2017]To explore the molecular basis of an individual with Bel variant of the ABO blood group.