Amyotrophic Lateral SclerosisPhase 1NCT03626012
A Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB078 in Adults With C9ORF72-Associated Amyotrophic Lateral Sclerosis
A Phase 1 study testing BIIB078 in people with Amyotrophic Lateral Sclerosis, run by Biogen at 21 sites in 6 countries.
Trial summary
The primary objective of this study is to evaluate the safety and tolerability of BIIB078 in adults with C9ORF72-Amyotrophic Lateral Sclerosis (ALS). The secondary objectives of this study are to evaluate the pharmacokinetic profile of BIIB078 and to evaluate the effects of BIIB078 on clinical function. 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?
- BIIB078
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 21 sitesin 6 countries
- Study dates
- 10 Sep 2018to 17 Nov 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Ability of the participant to understand the purpose and risks of the study, to provide signed and dated informed consent, and to authorize the use of confidential health information in accordance with national and local participant privacy regulations; or, in the event of the participant's physical incapacity to sign, to confirm that understanding and consent orally to a legally authorized representative (LAR) for the express purpose of having said informed consent and authorization signed on his/her behalf.
- All participants of childbearing potential must agree to practice highly effective contraception during the study and be willing and able to continue contraception for 5 months after their last dose of study treatment.
- Must meet the possible, laboratory-supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology El Escorial criteria and have documentation of a clinical genetic test demonstrating the presence of a pathogenic mutation in C9ORF72.
- Slow vital capacity (SVC) ≥ 50% of predicted value as adjusted for sex, age, and height (from the sitting position).
- Participants taking concomitant riluzole at study entry must be on a stable dose for ≥ 30 days prior to the first dose of study treatment (Day 1).
- 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).
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- ALS Cognitive Behavioral Screen (ALS-CBS) score ≥ 11 for the cognitive portion; ≥ 33 for the behavioral portion.
- Medically able to undergo the study procedures, and to adhere to the visit schedule at the time of study entry, as determined by the Investigator.
- 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.
Who cannot join
- History of drug abuse or alcoholism ≤ 6 months of Screening that would limit participation in the study, as determined by the Investigator.
- Tracheostomy.
- Prescreening ALSFRS-R slope less than 0.4 points/month, where prescreening ALSFRS-R slope is defined as follows: (48 - ALSFRS-R score at Screening) / (months from date of symptom onset to date of Screening).
- History of or positive test result at Screening for human immunodeficiency virus. .
- History of, or positive test result at Screening for, hepatitis C virus antibody.
- Treatment with another investigational drug or biological agent within 1 month of Screening or 5 half-lives of study agent, whichever is longer.
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- 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.
- Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system during the study period.
- Female participants who are pregnant or currently breastfeeding.
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
21 sites in 6 countries.
21 sites in 6 countries
United States12 sites
Research Site
Atlanta, Georgia, 30322
Research Site
Baltimore, Maryland, 21287
Research Site
Boston, Massachusetts, 02114
Research Site
Jacksonville, Florida, 32224
Research Site
Knoxville, Tennessee, 37920
Research Site
La Jolla, California, 92037-0886
Research Site
Lincoln, Nebraska, 68506-2960
Research Site
Los Angeles, California, 90048
Research Site
Miami, Florida, 33136
Research Site
New York, New York, 10032
Research Site
Palo Alto, California, 94303
Research Site
St Louis, Missouri, 63110
Canada3 sites
Research Site
Calgary, Alberta, T2N 1N4
Research Site
Montreal, Quebec, H3A 2B4
Research Site
Toronto, Ontario, M4N 3M5
United Kingdom3 sites
Research Site
London, Greater London, SE5 9RS
Research Site
London, NW1 2PG
Research Site
Sheffield, South Yorkshire, S10 2HQ
About this study
Official title: 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
The primary objective of this study is to evaluate the safety and tolerability of BIIB078 in adults with C9ORF72-Amyotrophic Lateral Sclerosis (ALS). The secondary objectives of this study are to evaluate the pharmacokinetic profile of BIIB078 and to evaluate the effects of BIIB078 on clinical function. As the first-in-human study, the study enrolls a small number of participants in each cohort. Every participant in a cohort is treated with the same dose or placebo. The study is designed to evaluate and confirm the safety of each dose before enrolling and exposing new participants to a higher dose in the next cohort.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- BIIB078, 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.
BIIB078Drug
Administered as specified in the treatment arm.
PlaceboDrug
Administered as specified in the treatment arm.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: BIIB078 First Dosage | Experimental | BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days. Receives: Drug: BIIB078 |
| Cohort 2: BIIB078 Second Dosage | Experimental | BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days. Receives: Drug: BIIB078 |
| Cohort 3: BIIB078 Third Dosage | Experimental | BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days. Receives: Drug: BIIB078 |
| Cohort 4: BIIB078 Fourth Dosage | Experimental | BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by five maintenance doses on five later days. Receives: Drug: BIIB078 |
| Cohort 5: BIIB078 Fifth Dosage | Experimental | BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by five maintenance doses on five later days. Receives: Drug: BIIB078 |
| Cohort 6: BIIB078 Sixth Dosage | Experimental | BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by five maintenance doses on five later days. Receives: Drug: BIIB078 |
| Cohorts 1-6: Placebo | Placebo comparator | Matching placebo will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days (Cohorts 1 through 3) and five maintenance doses on five later days (Cohorts 4 through 6). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, places participant at immediate risk of death, requires initial or prolonged inpatient hospitalization, results in persistent or significant disability/incapacity, results in congenital anomaly, is a medically important event.
Measured: Baseline through End of Study (Approximately Day 323)
Secondary outcomes (10)
Serum BIIB078 Concentration
Measured: Baseline and at multiple time points up to Day 260
Area Under the Concentration-Time Curve (AUC) from Time 0 to Infinity (AUCinf)
Measured: Baseline and at multiple time points up to Day 260
AUC from Time 0 to Time of the Last Measurable Concentration (AUClast)
Measured: Baseline and at multiple time points up to Day 260
Maximum Observed Concentration (Cmax)
Measured: Baseline and at multiple time points up to Day 260
Time to Reach Cmax (Tmax)
Measured: Baseline and at multiple time points up to Day 260
Terminal Elimination Half-Life (t 1/2)
Measured: Baseline and at multiple time points up to Day 260
Change from Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Scores
The ALSFRS-R has been demonstrated to predict survival. The ALSFRS-R measures 4 functional domains, including respiratory, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48 [Cedarbaum 1999], with higher scores representing better function.
Measured: Baseline up to Day 323
Change from Baseline in Percent of Predicted Slow Vital Capacity (SVC)
Measured: Baseline up to Day 260
Change from Baseline in Muscle Strength
Quantitative muscle strength will be evaluated using hand-held dynamometry (HHD), which tests isometric strength of multiple muscles using standard participant positioning. Approximately 8 muscle groups will be examined (per each side) in both upper and lower extremities.
Measured: Baseline up to Day 260
Change from Baseline in Bulbar Strength
Bulbar strength will be measured by the Iowa Oral Pressure Instrument (IOPI). The IOPI is a commercially available tongue pressure measurement system composed of an air-filled bulb connected to a pressure transducer. The bulb can be placed in different positions in the mouth in order to assess different aspects of tongue weakness.
Measured: Baseline up to Day 260
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2018
- Study start10 Sep 2018
- Primary completion17 Nov 2021
- Study completion17 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 106 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
- NCT03626012
- Sponsor's protocol ID
- 245AS101
- Other IDs
- 2017-000294-36, 2017
- Status last verified
- Jan 2022
- First submitted
- 7 Aug 2018
- Last updated
- 14 Jan 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
van den Berg LH, Rothstein JD, Shaw PJ, Babu S, Benatar M, Bucelli RC, Genge A, Glass JD, Hardiman O, Libri V, Mobach T, Oskarsson B, Pattee GL, Ravits J, Shaw CE, Weber M, Zinman L, Jafar-Nejad P, Rigo F, Lin L, Ferguson TA, Gotter AL, Graham D, Monine M, Inra J, Sinks S, Eraly S, Garafalo S, Fradette S. Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in adults with C9orf72-associated amyotrophic lateral sclerosis: a phase 1, randomised, double blinded, placebo-controlled, multiple ascending dose study. Lancet Neurol. 2024 Sep;23(9):901-912. doi: 10.1016/S1474-4422(24)00216-3. Epub 2024 Jul 23.
PubMed 39059407
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03626012
- Acronym / sponsor ID
- 245AS101
- Conditions
- Amyotrophic Lateral Sclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 10 Sep 2018 (actual)
- Primary completion
- 17 Nov 2021 (actual)
- Study completion
- 17 Nov 2021 (actual)
- First posted
- 10 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the safety and tolerability of BIIB078 in adults with C9ORF72-Amyotrophic Lateral Sclerosis (ALS). The secondary objectives of this study are to evaluate the pharmacokinetic profile of BIIB078 and to evaluate the effects of BIIB078 on clinical function. As the first-in-human study, the study enrolls a small number of participants in each cohort. Every participant in a cohort is treated with the same dose or placebo. The study is designed to evaluate and confirm the safety of each dose before enrolling and exposing new participants to a higher dose in the next cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: BIIB078 First Dosage | Experimental | Drug: BIIB078BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days. |
| Cohort 2: BIIB078 Second Dosage | Experimental | Drug: BIIB078BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days. |
| Cohort 3: BIIB078 Third Dosage | Experimental | Drug: BIIB078BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days. |
| Cohort 4: BIIB078 Fourth Dosage | Experimental | Drug: BIIB078BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by five maintenance doses on five later days. |
| Cohort 5: BIIB078 Fifth Dosage | Experimental | Drug: BIIB078BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by five maintenance doses on five later days. |
| Cohort 6: BIIB078 Sixth Dosage | Experimental | Drug: BIIB078BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by five maintenance doses on five later days. |
| Cohorts 1-6: Placebo | Placebo comparator | Drug: PlaceboMatching placebo will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days (Cohorts 1 through 3) and five maintenance doses on five later days (Cohorts 4 through 6). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Ability of the participant to understand the purpose and risks of the study, to provide signed and dated informed consent, and to authorize the use of confidential health information in accordance with national and local participant privacy regulations; or, in the event of the participant's physical incapacity to sign, to confirm that understanding and consent orally to a legally authorized representative (LAR) for the express purpose of having said informed consent and authorization signed on his/her behalf.
- All participants of childbearing potential must agree to practice highly effective contraception during the study and be willing and able to continue contraception for 5 months after their last dose of study treatment.
- Must meet the possible, laboratory-supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology El Escorial criteria and have documentation of a clinical genetic test demonstrating the presence of a pathogenic mutation in C9ORF72.
- Slow vital capacity (SVC) ≥ 50% of predicted value as adjusted for sex, age, and height (from the sitting position).
- Participants taking concomitant riluzole at study entry must be on a stable dose for ≥ 30 days prior to the first dose of study treatment (Day 1).
Key exclusion criteria (10 listed)
- History of drug abuse or alcoholism ≤ 6 months of Screening that would limit participation in the study, as determined by the Investigator.
- Tracheostomy.
- Prescreening ALSFRS-R slope less than 0.4 points/month, where prescreening ALSFRS-R slope is defined as follows: (48 - ALSFRS-R score at Screening) / (months from date of symptom onset to date of Screening).
- History of or positive test result at Screening for human immunodeficiency virus. .
- History of, or positive test result at Screening for, hepatitis C virus antibody.
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 |
|---|---|---|
| BIIB078Administered as specified in the treatment arm. | Drug | Cohort 1: BIIB078 First Dosage, Cohort 2: BIIB078 Second Dosage, Cohort 3: BIIB078 Third Dosage, Cohort 4: BIIB078 Fourth Dosage, Cohort 5: BIIB078 Fifth Dosage, Cohort 6: BIIB078 Sixth Dosage |
| PlaceboAdministered as specified in the treatment arm. | Drug | Cohorts 1-6: Placebo |
Primary outcome
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline through End of Study (Approximately Day 323)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, places participant at immediate risk of death, requires initial or prolonged inpatient hospitalization, results in persistent or significant disability/incapacity, results in congenital anomaly, is a medically important event.
10 secondary outcomes
Serum BIIB078 Concentration
Time frame: Baseline and at multiple time points up to Day 260
Area Under the Concentration-Time Curve (AUC) from Time 0 to Infinity (AUCinf)
Time frame: Baseline and at multiple time points up to Day 260
AUC from Time 0 to Time of the Last Measurable Concentration (AUClast)
Time frame: Baseline and at multiple time points up to Day 260
Maximum Observed Concentration (Cmax)
Time frame: Baseline and at multiple time points up to Day 260
Time to Reach Cmax (Tmax)
Time frame: Baseline and at multiple time points up to Day 260
Terminal Elimination Half-Life (t 1/2)
Time frame: Baseline and at multiple time points up to Day 260
Change from Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Scores
Time frame: Baseline up to Day 323
Change from Baseline in Percent of Predicted Slow Vital Capacity (SVC)
Time frame: Baseline up to Day 260
Change from Baseline in Muscle Strength
Time frame: Baseline up to Day 260
Change from Baseline in Bulbar Strength
Time frame: Baseline up to Day 260
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2022.
- Derived from this study: PubMed 39059407van den Berg LH, Rothstein JD, Shaw PJ, Babu S, Benatar M, Bucelli RC, Genge A, Glass JD, Hardiman O, Libri V, Mobach T, Oskarsson B, Pattee GL, Ravits J, Shaw CE, Weber M, Zinman L, Jafar-Nejad P, Rigo F, Lin L, Ferguson TA, Gotter AL, Graham D, Monine M, Inra J, Sinks S, Eraly S, Garafalo S, Fradette S. Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in adults with C9orf72-associated amyotrophic lateral sclerosis: a phase 1, randomised, double blinded, placebo-controlled, multiple ascending dose study. Lancet Neurol. 2024 Sep;23(9):901-912. doi: 10.1016/S1474-4422(24)00216-3. Epub 2024 Jul 23.
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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
21 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BIIB078 in people with Amyotrophic Lateral Sclerosis, run by Biogen at 21 sites in 6 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 10 inclusion and 10 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: finished, as of the sponsor's last update on 14 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Canada, United Kingdom, Ireland, Netherlands and 1 more country. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Baseline through End of Study (Approximately Day 323)). 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 NCT03626012, 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 14 Jan 2022.