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 PolyCAG Expansion in the ATXN2 Gene
- Conditions
- Amyotrophic lateral sclerosis (ALS)neurodegenerative disease10029317
- Registration Number
- NL-OMON52649
- Lead Sponsor
- Biogen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
Key Inclusion Criteria:
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.
- All women of childbearing potential and all men must ensure that highly
effective contraception is used during the study and for at least 6 months for
female participants and 8 months for male participants after their last dose of
study treatment.
- No known presence or family history of mutations in the the 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 Federati 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 cytosineadenine-
uanine/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.
- Slow vital capacity (SVC) criteria:
- 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 Cohorts 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 (Day1).
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 <br
Key Exclusion Criteria:
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.
- 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 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 symptomatic,
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; exc
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Part 1: Number of Participants with Adverse Events (AEs) and Serious<br /><br>Adverse Events (SAEs)<br /><br>Part 2: Number of Participants with AEs and SAEs</p><br>
- Secondary Outcome Measures
Name Time Method