Amyotrophic Lateral SclerosisPhase 1/2ALSpireNCT04494256
A Study to Assess the Safety, Tolerability, and Effect on Disease Progression of BIIB105 in Participants With Amyotrophic Lateral Sclerosis (ALS) and Participants With the ALS Ataxin-2 (ATXN2) Genetic Mutation
A Phase 1/2 study testing BIIB105 in people with Amyotrophic Lateral Sclerosis, run by Biogen at 17 sites in 4 countries.
Trial summary
The ALSpire Study is a clinical trial evaluating the investigational drug BIIB105 in adults living with amyotrophic lateral sclerosis (ALS). The ALSpire Study consists of two parts: Part 1: 6-month placebo-controlled study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- BIIB105
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 99 participants
- Where
- 17 sitesin 4 countries
- Study dates
- 28 Sep 2020to 13 Aug 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Part 1:
- Ability of the participant to understand the purpose and risks of the study and indicate informed consent, and the ability of the participant or the participant's legally authorized representative, to provide signed and dated informed consent and authorization to use protected health information in accordance with national and local privacy regulations.
- No known presence or family history of mutations in the superoxide dismutase 1 (SOD1) or fused in sarcoma (FUS) genes.
- Participants in Cohorts A, B, C1 and D1, must meet the laboratory-supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology El Escorial criteria (revised according to the Airlie House Conference 1998 [Brooks 2000]). Participants in Cohort C2 and D2, must meet any of the prior conditions, but may also only meet clinically possible criteria for diagnosing ALS, or exhibit weakness attributable to ALS in the presence of ataxin-2 protein (ATXN2) intermediate repeats.
- In participants in Cohorts C2 and D2, 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.
- Slow vital capacity (SVC) criteria:
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- In participants in Cohorts A, B, C1, and D1, SVC ≥60% of predicted value as adjusted for sex, age, and height (from the sitting position).
- In participants in Cohort C2 and D2, SVC ≥50% of predicted value as adjusted for sex, age, and height (from the sitting position).
- If taking riluzole, participant must be on a stable dose for ≥30 days prior to Day 1 and expected to remain at that dose until the final study visit, unless the Investigator determines that it should be discontinued for medical reasons, in which case it may not be restarted during the study.
- Participants taking concomitant edaravone at study entry must be on a stable dose for ≥60 days prior to the first dose of study treatment (Day 1). Participants taking concomitant edaravone must be willing to continue with the same dose regimen throughout the study, unless the Investigator determines that edaravone should be discontinued for medical reasons, in which case it may not be restarted during the study. Edaravone may not be administered on dosing days of this study.
- Screening values of coagulation parameters including platelet count, international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) should be within normal ranges.
- Has an informant/caregiver who, in the Investigator's judgment, has frequent and sufficient contact with the participant as to be able to provide accurate information about the participant's cognitive and functional abilities at screening.
- Part 2:
- Ability of the participant to understand the purpose and risks of the study and indicate informed consent, and the ability of the participant or the participant's legally authorized representative to provide signed and dated informed consent and authorization to use protected health information in accordance with national and local privacy regulations
- Participants must have completed Study NCT04494256 Part 1 through Week 25 (Day 175 Visit for Cohorts A, B, C1, C2; Day 176 Visit for Cohorts D1, D2). This inclusion criterion does not apply to a participant if Part 1 was terminated by the Sponsor before the participant reached Week 25.
- Participants from Cohorts A, B, C1, and C2 must have a washout of ≥16 weeks between the last dose of study treatment received in Study NCT04494256 Part 1 and the first dose of BIIB105 received in Study NCT04494256 Part 2. Participants from Cohorts D1 and D2 do not require a washout period.
- If taking riluzole, participant must be on a stable dose for ≥30 days prior to Day 1 and expected to remain at that dose until the final study visit, unless the Investigator determines that it should be discontinued for medical reasons, in which case it may not be restarted during the study.
- Participants taking concomitant edaravone at study entry must be on a stable dose for ≥60 days prior to the first dose of study treatment (Day 1). Participants taking concomitant edaravone must be willing to continue with the same dose regimen throughout the study, unless the Investigator determines that edaravone should be discontinued for medical reasons, in which case it may not be restarted during the study. Edaravone may not be administered on dosing days of this study.
- Screening values of coagulation parameters including platelet count, INR, PT, and aPTT should be within normal ranges.
Who cannot join
- Part 1:
- History or positive test result at Screening for human immunodeficiency virus (HIV).
- Current hepatitis C infection.
- Current hepatitis B infection.
- History of alcohol or substance abuse ≤6 months of Screening that would limit participation in the study, as determined by the Investigator.
- Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system during the study period.
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- Presence of tracheostomy.
- In participants from Cohorts A, B, C1, and D1, history of myocardial infarction, as determined by the Investigator.
- In participants from Cohorts A, B, C1, and D1, poorly controlled type 1 or 2 diabetes mellitus defined as hemoglobin A1c (HbA1c) ≥8% during Screening.
- In participants in Cohorts A, B, and C1, prescreening ALSFRS-R slope >-0.4 points/month, where prescreening ALSFRS-R slope is defined as: (ALSFRS-R score at Screening - 48) / (months from date of symptom onset to date of Screening). This criterion is not applicable for Cohorts C2, D1, and D2.
- Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs) or biological agent within 1 month or 5 half-lives of study agent, whichever is longer, before Screening.
- Treatment with an approved disease-modifying therapy for ALS other than riluzole or edaravone within 1 month or 5 half-lives of therapy, whichever is longer, before completion of screening.
- Treatment with an antiplatelet or anticoagulant therapy that cannot safely be interrupted for lumbar puncture (LP) according to local standard of care and/or institutional guidelines, in the opinion of the Investigator or Prescriber.
- Female participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study.
- Part 2:
- History or positive test result at Screening for HIV. If participants from Cohorts D1 and D2 who would seamlessly roll from Part 1 into Part 2 test positive for HIV during screening for Part 2 but are clinically asymptomatic, they may enroll in Part 2 at the discretion of the Investigator.
- Current hepatitis C infection. If participants from Cohorts D1 and D2 who would seamlessly roll from Part 1 into Part 2 test positive for hepatitis C during screening for Part 2 but are clinically asymptomatic, they may enroll in Part 2 at the discretion of the Investigator.
- Current hepatitis B infection. If participants from Cohorts D1 and D2 who would seamlessly roll from Part 1 into Part 2 test positive for hepatitis B during screening for Part 2 but are clinically asymptomatic, they may enroll in Part 2 at the discretion of the Investigator.
- History of alcohol or substance abuse ≤ 6 months of Screening that would limit participation in the study, as determined by the Investigator.
- Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system during the study period.
- In participants from Cohorts A, B, C1, and D1, history of myocardial infarction, as determined by the Investigator.
- In participants from Cohorts A, B, C1, and D1, poorly controlled type 1 or 2 diabetes mellitus defined as HbA1c ≥8% during Screening.
- Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs; excluding BIIB105) or biological agent within 1 month or 5 half-lives of study agent, whichever is longer, before Screening.
- Treatment with an antiplatelet or anticoagulant therapy that cannot safely be interrupted for LP according to local standard of care and/or institutional guidelines, in the opinion of the Investigator or Prescriber.
- Female participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study.
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
17 sites in 4 countries.
17 sites in 4 countries
United States14 sites
The Emory Clinic
Atlanta, Georgia, 30322
University of Colorado Hospital - Neuroscience Center -Anschutz Medical Campus
Aurora, Colorado, 80045
ALS Clinic - Department of Neurology, Neuromuscular Division, Johns Hopkins University, School of Medicine
Baltimore, Maryland, 21218
Massachusetts General Hospital
Boston, Massachusetts, 02114
Houston Methodist Neurological Institute
Houston, Texas, 77030
Mayo Clinic Florida
Jacksonville, Florida, 32224
University of California San Diego Medical Center
La Jolla, California, 92037
Orlando Health
Orlando, Florida, 32806
Stanford Neuromuscular Research Center
Palo Alto, California, 94305
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Barrow Neurological Institute
Phoenix, Arizona, 85013
University of Utah
Salt Lake City, Utah, 84132
Washington University, School of Medicine
St Louis, Missouri, 63110
Georgetown University
Washington D.C., District of Columbia, 20007-2113
Canada1 site
Montreal Neurological Institute-Hospital
Montreal, Quebec, H3A 2B4
About this study
Official title: A Phase 1/2 Multiple-Ascending-Dose Study With a Long-Term Open-Label Extension to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Effect on Disease Progression of BIIB105 Administered Intrathecally to Adults With Amyotrophic Lateral Sclerosis With or Without Poly-CAG Expansion in the ATXN2 Gene
The ALSpire Study is a clinical trial evaluating the investigational drug BIIB105 in adults living with amyotrophic lateral sclerosis (ALS).
The ALSpire Study consists of two parts:
Read more
- Part 1: 6-month placebo-controlled study. During Part 1, participants are randomly assigned to receive either BIIB105 or placebo in a 3:1 or 2:1 ratio (depending on the participant's assigned Cohort).
- Part 2: up to 3-year long-term open-label extension. During Part 2, all participants receive BIIB105.
The objectives of the study are to evaluate:
- The safety and tolerability of BIIB105 in people with ALS
- What the body does to BIIB105 (also called "pharmacokinetics")
- What BIIB105 does to the body (also called "pharmacodynamics")
- Whether BIIB105 can slow the worsening of clinical function
Read the detailed description
About BIIB105:
- BIIB105 is an investigational drug designed to reduce the levels of a protein called ATXN2. It is administered intrathecally (via a procedure called lumbar puncture).
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- BIIB105, Placebo
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIIB105Drug
Administered as specified in the treatment arm.
PlaceboDrug
Administered as specified in the treatment arm.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Cohort A | Experimental | 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. Receives: Drug: BIIB105 |
| Part 1: Cohort B | Experimental | 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. Receives: Drug: BIIB105 |
| Part 1: Cohort C1 | Experimental | 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. Receives: Drug: BIIB105 |
| Part 1: Cohort D1 | Experimental | 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. Receives: Drug: BIIB105 |
| Part 1: Cohort C2 | Experimental | 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. Receives: Drug: BIIB105 |
| Part 1: Cohort D2 | Experimental | 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. Receives: Drug: BIIB105 |
| Part 1: Cohorts A-D2: Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
| Part 2: Cohorts A-C2: Open-Label | Experimental | 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. Receives: Drug: BIIB105 |
| Part 2: Cohorts D1, D2: Open-Label | Experimental | 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. Receives: Drug: BIIB105 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. A TEAE/TESAE was defined as any AE/SAE with an onset date that is on or after the first dose of study drug or any pre-existing condition that has worsened in severity after the first dose of study drug.
Measured: From first dose of the study drug in Part 1 up to end of follow up period in Part 1 (up to Day 260)
Part 2: Number of Participants With TEAEs and TESAEs
An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. A TEAE/TESAE was defined as any AE/SAE with an onset date that is on or after the first dose of study drug or any pre-existing condition that has worsened in severity after the first dose of study drug.
Measured: From first dose of the study in Part 2 up to end of follow up period in Part 2 (up to Day 1184)
Secondary outcomes (17)
Part 1: Serum Concentrations of BIIB105
Measured: Pre-dose and 1, 2, 4, 6 hours post-dose on days 1, 15, 29, 57, 85,113, 141, 169 and on days 2, 8, 92, and 176
Part 1: CSF Concentrations of BIIB105
Measured: Pre-dose on Days 1, 15, 29, 57, 85, 113, 141, 169, and on days 92, 130, 175, and 176
Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf)
AUCinf is the area under the serum concentration-time profile from time 0 extrapolated to infinite time. AUCinf was reported following dose 1 as planned.
Measured: Day 1
Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast)
AUClast was reported following dose 1 as planned.
Measured: Day 1
Part 1: Maximum Observed Serum Concentration (Cmax)
Measured: Days 1, 15, 29, 57, 85, 113, 141 and 169
Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax)
Measured: Days 1, 15, 29, 57, 85, 113, 141 and 169
Part 1: Elimination Half-Life (t1/2) in Serum
Elimination half-life (t1/2) was reported following dose 1 as planned.
Measured: Day 1
Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline
Plasma NfL ratio to baseline was reported in terms of geometric mean ratio.
Measured: Days 29, 57, 85, 113, 130 (For cohorts A, B, C1 and C2)/141 (For cohorts D1 and D2), 169 (For cohorts A, B, C1 and C2)/175 (For cohorts D1 and D2) and 241
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105
Measured: Predose on Days 1,15,29,57,85 and on Days 1,15,29,57,85,113,141,169.176,197,210,225,253,281,309,337,365,393,420,448,476,504,532,560,588,616,644,672,700,726,728
Integrated Part 1 and Part 2: Serum Concentration of BIIB105
Measured: Up to Day 176
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline
Plasma NfL ratio to baseline was reported in terms of geometric mean ratio.
Measured: Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449, 477, 505, 533, 561, 589, 617, 645, 673, 701
Integrated Part 1 and Part 2: Change From Baseline in Percent Predicted Slow Vital Capacity (SVC)
Vital capacity was measured by means of the slow vital capacity (SVC) test using a facemask with the participant sitting upright. SVC was determined by performing at least 3 trials. If the difference between the two highest values of the three trials was ≥10%, then up to 5 trials were performed. The highest percent predicted SVC value at each visit was used for the analysis. Here, baseline is defined as Part 1 day 1 value prior to the study drug. As specified in SAP, change from baseline at Week 40 (Day 281) in least square means and corresponding standard errors was summarized using the analysis of covariance (ANCOVA) model. Negative change from baseline indicates decrease in lung function.
Measured: Baseline, Day 281
Integrated Part 1 and Part 2: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score
The ALSFRS-R is a questionnaire that measured degree of impairment in 4 functional domains: respiratory function, bulbar function, gross motor skills, and fine motor skills. Each domain consists of 3 items, each scored from 0 to 4, with higher scores representing better function. Each domain score can have maximum score of 12 calculated as the sum of scores of 3 items for that domain and the total possible score for ALSFRS-R is 48. The total score is the sum of the 4 functional domain scores or all individual item scores if no missing item scores are present. Here, baseline is defined as Part 1 day 1 value prior to the study drug Negative change from baseline indicates disease progression. As specified in SAP change from baseline at Week 40 (Day 281) in least square means and corresponding standard errors was summarized using the ANCOVA model.
Measured: Baseline, Day 281
Integrated Part 1 and Part 2: Change From Baseline in Muscle Strength as Measured by Handheld Dynamometry (HHD) Megascore
Quantitative muscle strength was evaluated using HHD, which tested the isometric strength of multiple muscles using standard participant positioning. Approximately 8 muscle groups were examined (per each side) in both upper and lower extremities. The muscle strength values were normalized to Z scores as (post-baseline measurements -mean)/SD and averaged to provide HHD overall megascore. The overall megascore was created by averaging Z scores, if no more than 14 (≤ 14) measures are missing. A Z-score (also called a standard score) is a way to describe how far and in what direction a data point is from the mean of the dataset (in this case, positive values indicate strength and negative values indicate weakness). A Z-score of 0 indicates the population mean, and a positive score indicates muscle strength. A negative change from baseline indicated decreased muscle strength.
Measured: Baseline, Day 281
Integrated Part 1 and Part 2: Time to Death or Permanent Ventilation
Time to death or permanent ventilation is defined as the time from first dose to death or permanent ventilation ( ≥ 22 hours of mechanical ventilation [invasive or noninvasive] per day for ≥ 21 consecutive days), whichever comes first. Participants who did not meet the endpoint definition were censored on the date of participant's last contact in Part 1 or Part 2. Time to death or permanent ventilation data was summarized using Kaplan-Meier curves based on randomization in Part 1.
Measured: Baseline up to Day 1184
Integrated Parts 1 and 2: Time to Death
Time to death was defined as the time from first dose to death.
Measured: Baseline up to Day 1184
Integrated Part 1 and Part 2: Time to Death, Incorporating Post-Study Withdrawal or Study Completion Vital Status Data
Measured: Up to Day 1184
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2020
- Study start28 Sep 2020
- Primary completion13 Aug 2024
- Study completion13 Aug 2024
Why it stopped: Sponsor's decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04494256
- Sponsor's protocol ID
- 275AS101
- Other IDs
- 2020-000207-36
- Acronym
- ALSpire
- Status last verified
- Sep 2025
- First submitted
- 30 Jul 2020
- Last updated
- 9 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
Publications
Kim G, Nakayama L, Blum JA, Akiyama T, Boeynaems S, Chakraborty M, Couthouis J, Tassoni-Tsuchida E, Rodriguez CM, Bassik MC, Gitler AD. Genome-wide CRISPR screen reveals v-ATPase as a drug target to lower levels of ALS protein ataxin-2. Cell Rep. 2022 Oct 25;41(4):111508. doi: 10.1016/j.celrep.2022.111508.
PubMed 36288714
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Multiple-Ascending-Dose Study With a Long-Term Open-Label Extension to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Effect on Disease Progression of BIIB105 Administered Intrathecally to Adults With Amyotrophic Lateral Sclerosis With or Without Poly-CAG Expansion in the ATXN2 Gene
- ClinicalTrials.gov ID
- NCT04494256
- Acronym / sponsor ID
- ALSpire / 275AS101
- Conditions
- Amyotrophic Lateral Sclerosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision
- Enrolment
- 99 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 28 Sep 2020 (actual)
- Primary completion
- 13 Aug 2024 (actual)
- Study completion
- 13 Aug 2024 (actual)
- First posted
- 31 Jul 2020 (actual)
- Results
- Posted 9 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The ALSpire Study is a clinical trial evaluating the investigational drug BIIB105 in adults living with amyotrophic lateral sclerosis (ALS).
The ALSpire Study consists of two parts:
- Part 1: 6-month placebo-controlled study. During Part 1, participants are randomly assigned to receive either BIIB105 or placebo in a 3:1 or 2:1 ratio (depending on the participant's assigned Cohort).
- Part 2: up to 3-year long-term open-label extension. During Part 2, all participants receive BIIB105.
The objectives of the study are to evaluate:
- The safety and tolerability of BIIB105 in people with ALS
- What the body does to BIIB105 (also called "pharmacokinetics")
- What BIIB105 does to the body (also called "pharmacodynamics")
- Whether BIIB105 can slow the worsening of clinical function
Detailed description
About BIIB105:
- BIIB105 is an investigational drug designed to reduce the levels of a protein called ATXN2. It is administered intrathecally (via a procedure called lumbar puncture).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Part 1: Cohort A | Experimental | Drug: BIIB105Participants 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. |
| Part 1: Cohort B | Experimental | Drug: BIIB105Participants 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. |
| Part 1: Cohort C1 | Experimental | Drug: BIIB105Participants 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. |
| Part 1: Cohort D1 | Experimental | Drug: BIIB105Participants 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. |
| Part 1: Cohort C2 | Experimental | Drug: BIIB105Participants 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. |
| Part 1: Cohort D2 | Experimental | Drug: BIIB105Participants 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. |
| Part 1: Cohorts A-D2: Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
| Part 2: Cohorts A-C2: Open-Label | Experimental | Drug: BIIB105Participants 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. |
| Part 2: Cohorts D1, D2: Open-Label | Experimental | Drug: BIIB105Participants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Ability of the participant to understand the purpose and risks of the study and indicate informed consent, and the ability of the participant or the participant's legally authorized representative, to provide signed and dated informed consent and authorization to use protected health information in accordance with national and local privacy regulations.
- No known presence or family history of mutations in the superoxide dismutase 1 (SOD1) or fused in sarcoma (FUS) genes.
- Participants in Cohorts A, B, C1 and D1, must meet the laboratory-supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology El Escorial criteria (revised according to the Airlie House Conference 1998 [Brooks 2000]). Participants in Cohort C2 and D2, must meet any of the prior conditions, but may also only meet clinically possible criteria for diagnosing ALS, or exhibit weakness attributable to ALS in the presence of ataxin-2 protein (ATXN2) intermediate repeats.
- In participants in Cohorts C2 and D2, 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.
- Slow vital capacity (SVC) criteria:
Key exclusion criteria (26 listed)
- History or positive test result at Screening for human immunodeficiency virus (HIV).
- Current hepatitis C infection.
- Current hepatitis B infection.
- History of alcohol or substance abuse ≤6 months of Screening that would limit participation in the study, as determined by the Investigator.
- Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system during the study period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIIB105Administered as specified in the treatment arm. | Drug | Part 1: Cohort A, Part 1: Cohort B, Part 1: Cohort C1, Part 1: Cohort C2, Part 1: Cohort D1, Part 1: Cohort D2, Part 2: Cohorts A-C2: Open-Label, Part 2: Cohorts D1, D2: Open-Label |
| PlaceboAdministered as specified in the treatment arm. | Drug | Part 1: Cohorts A-D2: Placebo |
Primary outcome
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Time frame: From first dose of the study drug in Part 1 up to end of follow up period in Part 1 (up to Day 260)
An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. A TEAE/TESAE was defined as any AE/SAE with an onset date that is on or after the first dose of study drug or any pre-existing condition that has worsened in severity after the first dose of study drug.
Part 2: Number of Participants With TEAEs and TESAEs
Time frame: From first dose of the study in Part 2 up to end of follow up period in Part 2 (up to Day 1184)
An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. A TEAE/TESAE was defined as any AE/SAE with an onset date that is on or after the first dose of study drug or any pre-existing condition that has worsened in severity after the first dose of study drug.
17 secondary outcomes
Part 1: Serum Concentrations of BIIB105
Time frame: Pre-dose and 1, 2, 4, 6 hours post-dose on days 1, 15, 29, 57, 85,113, 141, 169 and on days 2, 8, 92, and 176
Part 1: CSF Concentrations of BIIB105
Time frame: Pre-dose on Days 1, 15, 29, 57, 85, 113, 141, 169, and on days 92, 130, 175, and 176
Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf)
Time frame: Day 1
Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast)
Time frame: Day 1
Part 1: Maximum Observed Serum Concentration (Cmax)
Time frame: Days 1, 15, 29, 57, 85, 113, 141 and 169
Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax)
Time frame: Days 1, 15, 29, 57, 85, 113, 141 and 169
Part 1: Elimination Half-Life (t1/2) in Serum
Time frame: Day 1
Part 1: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline
Time frame: Days 29, 57, 85, 113, 130 (For cohorts A, B, C1 and C2)/141 (For cohorts D1 and D2), 169 (For cohorts A, B, C1 and C2)/175 (For cohorts D1 and D2) and 241
Integrated Part 1 and Part 2: CSF PK Concentration of BIIB105
Time frame: Predose on Days 1,15,29,57,85 and on Days 1,15,29,57,85,113,141,169.176,197,210,225,253,281,309,337,365,393,420,448,476,504,532,560,588,616,644,672,700,726,728
Integrated Part 1 and Part 2: Serum Concentration of BIIB105
Time frame: Up to Day 176
Integrated Part 1 and Part 2: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline
Time frame: Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449, 477, 505, 533, 561, 589, 617, 645, 673, 701
Integrated Part 1 and Part 2: Change From Baseline in Percent Predicted Slow Vital Capacity (SVC)
Time frame: Baseline, Day 281
Integrated Part 1 and Part 2: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score
Time frame: Baseline, Day 281
Integrated Part 1 and Part 2: Change From Baseline in Muscle Strength as Measured by Handheld Dynamometry (HHD) Megascore
Time frame: Baseline, Day 281
Integrated Part 1 and Part 2: Time to Death or Permanent Ventilation
Time frame: Baseline up to Day 1184
Integrated Parts 1 and 2: Time to Death
Time frame: Baseline up to Day 1184
Integrated Part 1 and Part 2: Time to Death, Incorporating Post-Study Withdrawal or Study Completion Vital Status Data
Time frame: Up to Day 1184
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36288714Kim G, Nakayama L, Blum JA, Akiyama T, Boeynaems S, Chakraborty M, Couthouis J, Tassoni-Tsuchida E, Rodriguez CM, Bassik MC, Gitler AD. Genome-wide CRISPR screen reveals v-ATPase as a drug target to lower levels of ALS protein ataxin-2. Cell Rep. 2022 Oct 25;41(4):111508. doi: 10.1016/j.celrep.2022.111508.
- Biogen Trial LinkLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Biogen
17 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BIIB105 in people with Amyotrophic Lateral Sclerosis, run by Biogen at 17 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Canada, Italy, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) (time frame: From first dose of the study drug in Part 1 up to end of follow up period in Part 1 (up to Day 260)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04494256, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2025; AzTrials last refreshed its copy on 30 Oct 2026.