What side effects are associated with this type of intervention?

Common treatments for ALS, including investigational drugs like BIIB105, often aim to slow disease progression. Known side effects of similar treatments can include gastrointestinal issues (nausea, diarrhea), fatigue, and potential liver enzyme abnormalities. Specific investigational drugs like zilucoplan and verdiperstat have shown side effects such as injection site reactions and gastrointestinal disturbances. It is important for patients to discuss potential side effects with their healthcare provider to manage and mitigate these risks effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Amyotrophic Lateral Sclerosis (ALS), primarily aimed at slowing disease progression and managing symptoms. Riluzole, approved in 1995, was the first drug shown to extend survival. Edaravone, approved in 2017, has been shown to slow the decline in daily functioning. These treatments are somewhat similar to BIIB105, which is currently being studied for its potential to slow ALS progression by targeting specific genetic mutations and disease mechanisms.

What other types of research exist?

Promising novel alternatives to BIIB105 for ALS patients include Tofersen, an antisense oligonucleotide targeting SOD1 mutations, and AMX0035, a combination of sodium phenylbutyrate and taurursodiol, which has shown potential in slowing disease progression. Additionally, Reldesemtiv, a fast skeletal muscle troponin activator, is being investigated for its ability to improve muscle function in ALS patients.

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Monoclonal Antibodies

BIIB105 for ALS (ALSpire Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by Biogen

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Confirmed intermediate cytosine-adenine-guanine/cytosine-adenine-adenine (CAG/CAA) repeat expansion in the ataxin-2 (ATXN2) gene as defined by at least 1 allele carrying 30 to 33 CAG/CAA repeats

In participants in Cohorts C2 and D2, confirmed intermediate cytosine-adenine-guanine/cytosine-adenine-adenine (CAG/CAA) repeat expansion in the ataxin-2 gene or RNA (ATXN2) gene as defined by at least 1 allele carrying 30 to 33 CAG/CAA repeats.

Must not have

Current hepatitis C infection

Female participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to day 1184

Summary

This trial is testing BIIB105, a new drug for adults with ALS. The drug aims to lower a protein that may worsen ALS, and it is given through an injection into the spinal fluid.

Who is the study for?

This trial is for adults with ALS, including those with a specific ATXN2 gene mutation. Participants must understand the study and give informed consent, have stable doses of certain ALS medications before starting, and meet criteria for diagnosing ALS. They need an informant/caregiver and should not have certain genetic mutations or history of substance abuse.

What is being tested?

The ALSpire Study tests BIIB105's safety and effects on ALS progression over two parts: a 6-month phase where participants are randomly given either BIIB105 or placebo, followed by up to three years where all receive BIIB105. The study looks at how the body processes the drug and its impact on clinical function.

What are the potential side effects?

Specific side effects aren't listed here but generally include reactions related to drug tolerance in organs, potential infusion-related issues, changes in blood parameters that will be closely monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My genetic test shows 30-33 repeats in the ATXN2 gene.

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I have a specific genetic mutation in the ATXN2 gene.

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I don't have, nor does my family, mutations in the SOD1 or FUS genes.

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I don't have, nor does my family, mutations in the SOD1 or FUS genes.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently infected with hepatitis C.

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I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

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My diabetes is not well-managed, with an HbA1c level of 8% or higher.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to day 1184

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to day 1184

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to day 1184 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Part 2: Number of Participants with AEs and SAEs

Secondary study objectives

Integrated Parts 1 and 2: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score

Integrated Parts 1 and 2: Change From Baseline in Muscle Strength, as Measured by Handheld Dynamometry (HHD)

Continuous Positive Airway Pressure

Trial Design

9Treatment groups

Experimental Treatment

Placebo Group

Group I: Part 2: Cohorts D1, D2: Open-LabelExperimental Treatment1 Intervention

Participants who complete Cohorts D1 and D2 will have a blinded Loading Dose Period, during which those who received placebo in Part 1 will receive BIIB105 Dose 4, IT, as 3 loading doses on Day 1 and two later days, while those who received BIIB105 in Part 1 will receive 2 loading doses of BIIB105 Dose 4, IT, on Days 1 and one later day, and placebo on Day 15. After the blinded Loading Dose Period, participants will receive BIIB105 Dose 4 up to thirty-eight maintenance doses, on up to thirty-eight later days.

Group II: Part 2: Cohorts A-C2: Open-LabelExperimental Treatment1 Intervention

Participants who complete Cohorts A, B, C1, and C2 will receive BIIB105 Dose 3, IT, as 3 loading doses on Day 1 and two later days, followed up to thirty-eight maintenance doses, on up to thirty-eight later days.

Group III: Part 1: Cohort D2Experimental Treatment1 Intervention

Participants with polyQ-ALS will receive BIIB105 Dose 4, IT, as 3 loading doses on Day 1 and two later days, followed by five maintenance doses on five later days.

Group IV: Part 1: Cohort D1Experimental Treatment1 Intervention

Participants with ALS will receive BIIB105 Dose 4, IT, as 3 loading doses on Day 1 and two later days, followed by five maintenance doses on five later days.

Group V: Part 1: Cohort C2Experimental Treatment1 Intervention

Participants with polyQ-ALS will receive BIIB105 Dose 3, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.

Group VI: Part 1: Cohort C1Experimental Treatment1 Intervention

Participants with ALS will receive BIIB105 Dose 3, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.

Group VII: Part 1: Cohort BExperimental Treatment1 Intervention

Participants with ALS will receive BIIB105 Dose 2, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.

Group VIII: Part 1: Cohort AExperimental Treatment1 Intervention

Participants with ALS will receive BIIB105 Dose 1, intrathecally (IT), as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.

Group IX: Part 1: Cohorts A-D2: PlaceboPlacebo Group1 Intervention

Participants with ALS and polyQ-ALS for Cohorts A, B, C1 and C2 will receive matching placebo to BIIB105 as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days, and participants with ALS and polyQ-ALS for Cohorts D1 and D2 will receive matching placebo to BIIB105 as 3 loading doses on Day 1 and two later days, followed by five maintenance doses on five later days.

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The investigational drug BIIB105, like other treatments for ALS, aims to slow disease progression by targeting specific pathways involved in neurodegeneration. BIIB105 is designed to reduce the production of toxic proteins that contribute to motor neuron death. Similar treatments, such as sodium phenylbutyrate-taurursodiol (PB-TURSO), work by reducing neuronal cell death through different mechanisms, including reducing oxidative stress and mitochondrial dysfunction. These mechanisms are crucial for ALS patients as they help preserve motor neuron function, potentially slowing the decline in muscle strength and respiratory function, thereby improving quality of life and extending survival.