Amyotrophic Lateral SclerosisPhase 1/2HORIZONNCT07855211
A Study to Learn About the Safety of BIIB147 and Its Effects in Adults With Amyotrophic Lateral Sclerosis (ALS)
A Phase 1/2 study testing BIIB147 in people with Amyotrophic Lateral Sclerosis, run by Biogen at 2 sites in United States.
Trial summary
In this study, researchers will learn more about the effects of BIIB147, in participants with amyotrophic lateral sclerosis, also known as ALS. ALS is a rare disease that damages the motor neurons in the brain and spinal cord that help control the movement of muscles in the body. 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?
- BIIB147
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 2 sitesUnited States
- Study dates
- 7 Oct 2026to 23 Jan 2034
- Phase
- Phase 1/2
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
- MAD Period
- Participants must have a diagnosis of ALS consistent with the Gold Coast criteria.
- No pathogenic variants, likely pathogenic variants, or variants of uncertain significance in the superoxide dismutase 1 (SOD1) or fused in sarcoma (FUS) genes (confirmed by central genetic testing).
- Greater than or equal to (≥) 50% of predicted value for slow vital capacity (SVC) 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 end of study (EOS)/early termination (ET), unless the Investigator determines that it should be discontinued for medical reasons, in which case it may not be restarted during the study.
- OLE
- Participants must have completed Study 303AS101 MAD period; all pre-dose assessments for the end of MAD treatment period visit (Day 113 for Cohorts A, B, C, and Day 169 for Cohort D) must be completed prior to dosing in OLE.
Who cannot join
- MAD Period
- History or positive test result at screening for human immunodeficiency virus (HIV). The requirement for testing at screening may be omitted if it is not permitted by local regulations.
- History of confounding neuromuscular or neurological disorder that is expected to have a progressive (i.e., worsening) course during the study, and/or is expected to be associated with elevations in NfL, in the opinion of the Investigator.
- Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system during the study period.
- Requires permanent ventilation (using > 22 hours per day [h/day] invasive or non-invasive ventilation)
- History of a deep venous thrombosis or pulmonary embolism ≤2 years of screening, or since the date of ALS diagnosis, whichever is longer.
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- Treatment with an approved ALS disease-modifying therapy other than riluzole or edaravone, or another investigational drug (including investigational drugs for ALS through compassionate use programs), biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer, before completion of Screening.
- Current enrollment or a plan to enroll in any interventional clinical study. Participation in a noninterventional study focused on ALS natural history may be allowed at the discretion of the Investigator and after consultation with the Sponsor.
- OLE
- Any new condition or worsening of an existing condition that, according to the Investigator, would make the participant unsuitable for inclusion, could interfere with the assessment of safety, or would compromise the ability of the participant to undergo study procedures.
- Clinically significant abnormalities (based on most recent assessments in MAD period) in hematology, blood chemistry parameters, or 12-lead electrocardiogram (ECG) prior to first OLE visit that would make the participant unsuitable for inclusion as assessed by the Investigator.
- Note: Other protocol-defined Inclusion/Exclusion criteria do apply.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Global Biogen Clinical Trial Center contact
United States2 sites, 2 recruiting
- Recruiting
Austin Neuromuscular Center_Austin
Austin, Texas, 78759
512-920-0140
Yessar Hussain
- Recruiting
Washington University School of Medicine_St. Louis
St Louis, Missouri, 63110
314-362-6981
Sean Smith
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled MAD Study With Open-Label Extension to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of BIIB147 Administered Intrathecally to Adult Participants With ALS
In this study, researchers will learn more about the effects of BIIB147, in participants with amyotrophic lateral sclerosis, also known as ALS. ALS is a rare disease that damages the motor neurons in the brain and spinal cord that help control the movement of muscles in the body. It is a progressive disease, which means that it gets worse with time. Over time, this causes increasing problems with speaking, swallowing, moving the arms and legs, and breathing. In the case of ALS, this eventually leads to death from patients not being able to breathe.
This is a "first-in-human" study. This means that this study drug will be given to people for the very first time in this study. These studies are important because they help researchers learn about the safety of the study drug, how the body processes it, and what dose might be appropriate before testing it in larger groups.
Read more
The main goal of the study is to learn about the safety of BIIB147 in adult participants with ALS. The main question researchers want to answer is:
- How many participants have adverse events and serious adverse events during the study? Adverse events are health problems that may or may not be caused by the study drug.
- Researchers will also learn more about:
- How much BIIB147 gets into the blood?
- What is the highest amount of BIIB147 found in the blood?
- How long does it take BIIB147 to reach its highest amount in the blood?
- How much neurofilament light chain (NfL) protein is found in the blood?
- How longer-term treatment with BIIB147 affects disease worsening and the participants' overall survival?
This study will be done as follows:
- Participants will join the study after signing an informed consent form, also known as an ICF.
- Participants will be screened to check if they can join the study. The screening period will be up to 4 weeks.
- Participants will be randomly assigned to get either the study drug BIIB147 or a placebo during the main treatment period. A placebo is something that looks like the study drug but does not contain any medicine. A placebo is also given the same as the study drug.
- Neither the participants nor the researchers will know if participants are getting the study drug or the placebo.
- BIIB147 or the placebo will be given through a lumbar puncture. This is done using a thin needle that is put into the lower part of the spine.
- During the main treatment period, participants will have regular clinic visits and phone calls. At the visits, the study doctor will do tests to check the participants' overall health, including their brain and nerve function. The participants' breathing function, tongue strength, and muscle strength will also be checked. They will also measure the participants' height, weight, and vital signs and collect blood and urine samples. Participants will also complete questionnaires or answer questions about how they are feeling and about their daily lives.
- After finishing treatment in the main part of the study, some participants who qualify may be able to join a "long-term extension" part of the study. This may last up to 6 years or more. During this part of the study, all participants will get BIIB147.
- After the long-term extension is done, participants will join a follow-up safety period. If participants do not enter the long-term extension, they will go directly into the follow-up safety period once the treatment period is done.
- Each participant will be in the study for up to 8 years or more.
Read the detailed description
The primary objectives of this study are to evaluate the safety and tolerability of BIIB147 during the MAD Period and the long-term safety and tolerability of BIIB147 during the Open Label Extension (OLE) and the Integrated MAD and OLE Periods.
The secondary objectives of MAD Period are to evaluate the pharmacokinetics (PK) profile of total active BIIB147 related species in serum and cerebrospinal fluid (CSF), and to evaluate the impact of BIIB147 on neurodegeneration. The secondary objective for the OLE is to evaluate the long-term PK profile of total active BIIB147 related species in serum and CSF. The secondary objectives of the Integrated MAD Period and OLE are to evaluate the long-term impact of BIIB147 on neurodegeneration, on clinical outcomes of disease progression and survival for participants with earlier initiation of BIIB147 (i.e., start of MAD), compared with delayed initiation of BIIB147 (i.e., at start of the OLE), and long-term PK profile of total active BIIB147 related species in serum and CSF.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- BIIB147, 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.
BIIB147Drug
Administered intrathecally (IT)
PlaceboDrug
Administered IT
| Study group | Role | What they receive |
|---|---|---|
| MAD: Cohort A | Experimental | Participants will either receive Dose A of BIIB147 or a placebo for 12 weeks. Receives: Drug: BIIB147; Drug: Placebo |
| MAD: Cohort B | Experimental | Participants will either receive Dose B of BIIB147 or a placebo for 12 weeks. Receives: Drug: BIIB147; Drug: Placebo |
| MAD: Cohort C | Experimental | Participants will either receive Dose C of BIIB147 or a placebo for 12 weeks. Receives: Drug: BIIB147; Drug: Placebo |
| MAD: Cohort D | Experimental | Participants will either receive Dose D of BIIB147 or a placebo for 20 weeks. Receives: Drug: BIIB147; Drug: Placebo |
| OLE | Experimental | Participants from Cohorts A-D who complete the MAD period will enter a 4-week blinded loading-dose period. During this period, participants randomized to BIIB147 in the MAD period will receive placebo, followed by BIIB147, while participants randomized to placebo during the MAD period will receive BIIB147. Upon completion of the blinded loading-dose period, all participants will enter the open-label maintenance dose period and receive BIIB147 for up to 340 weeks. Receives: Drug: BIIB147; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
MAD, OLE, Integrated MAD and OLE Periods: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measured: Up to Week 416
Secondary outcomes (16)
MAD, OLE, Integrated MAD and OLE Periods: Serum Concentrations of Total Active BIIB147 Related Species
Measured: Pre-dose and at multiple time points post-dose [MAD: Up to Week 16 (Cohorts A, B, and C) and Up to Week 24 (Cohort D); OLE and Integrated MAD and OLE: Up to Week 340
MAD, OLE, Integrated MAD and OLE Periods: Cerebrospinal Fluid (CSF) Concentrations of Total Active BIIB147 Related Species
Measured: Pre-dose at multiple timepoints [MAD: Up to Week 16 (Cohorts A, B, and C) and Up to Week 24 (Cohort D); OLE and Integrated MAD and OLE: Up to Week 340]
MAD Period: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf) of BIIB147
Measured: Pre-dose and at multiple time points post-dose [Up to Week 16 (Cohorts A, B, and C) and Up to Week 24 (Cohort D)]
MAD Period: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUC0-last) of BIIB147
Measured: Pre-dose and at multiple time points post-dose [Up to Week 16 (Cohorts A, B, and C) and Up to Week 24 (Cohort D)]
MAD Period: Maximum Observed Serum Concentration (Cmax) of BIIB147
Measured: Pre-dose and at multiple time points post-dose [Up to Week 16 (Cohorts A, B, and C) and Up to Week 24 (Cohort D)]
MAD Period: Time to Reach Maximum Observed Serum Concentration (Tmax) of BIIB147
Measured: Pre-dose and at multiple time points post-dose [Up to Week 16 (Cohorts A, B, and C) and Up to Week 24 (Cohort D)]
MAD Period: Elimination Half-Life (t1/2) of BIIB147
Measured: Pre-dose and at multiple time points post-dose [Up to Week 16 (Cohorts A, B, and C) and Up to Week 24 (Cohort D)]
MAD, Integrated MAD and OLE Periods: Change From Baseline in Plasma Concentration of Neurofilament Light Chain (NfL)
Measured: Baseline, Week 16 (Cohorts A, B, and C), Week 24 (Cohort D), and Up to Week 340 (Integrated MAD and OLE)
Integrated MAD and OLE Period: Change From Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score
Measured: Baseline, Up to Week 340
Integrated MAD and OLE Period: Change From Baseline in Percent Predicted Slow Vital Capacity (SVC)
Measured: Baseline, Up to Week 340
Integrated MAD and OLE Period: Change From Baseline in Muscle Strength as Measured by Handheld Dynamometry (HHD)
Measured: Baseline, Up to Week 340
Integrated MAD and OLE Period: Change From Baseline in Bulbar Strength as Measured by Iowa Oral Pressure Instrument (IOPI)
Measured: Baseline, Up to Week 340
Integrated MAD and OLE Period: Change From Baseline in Rasch Overall Amyotrophic Lateral Sclerosis (ALS) Disability (ROADS).
Measured: Baseline, Up to Week 340
Integrated MAD and OLE Period: Change From Baseline in Weight
Measured: Baseline, Up to Week 340
Integrated MAD and OLE Period: Time to Death or Permanent Ventilation
Permanent ventilation is defined as ≥ 22 hours of mechanical ventilation [invasive or noninvasive] per day for ≥ 21 consecutive days.
Measured: Up to Week 416
Integrated MAD and OLE Period: Time to Death
Measured: Up to Week 416
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2026
- Study start7 Oct 2026
- Primary completion23 Jan 2034 (estimated)
- Study completion23 Jan 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 69 participants (estimated)
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
- NCT07855211
- Sponsor's protocol ID
- 303AS101
- Other IDs
- 2026-527124-27
- Acronym
- HORIZON
- Status last verified
- Oct 2026
- First submitted
- 28 Sep 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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/