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

Completed

Conditions: Amyotrophic lateral sclerosis
neurodegenerative disease
10029317

Registration Number: NL-OMON55647

Lead Sponsor: Biogen

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 3

Inclusion Criteria

- 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).
- 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.

Exclusion Criteria

- 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 point/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.
- 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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Number of Participants with adverse and serious adverse events.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>* Serum BIIB078 concentrations<br /><br>* Serum PK parameters:<br /><br>* Area under the concentration-time curve (AUC) from time 0 to infinity<br /><br>* AUC from time 0 to time of the last measurable concentration<br /><br>* Maximum observed concentration (Cmax)<br /><br>* Time to reach Cmax<br /><br>* Terminal elimination half-life (t)<br /><br>An additional secondary objective is to evaluate the effects of BIIB078 on<br /><br>clinical function.<br /><br>The additional secondary endpoints that relate to this objective are as follows:<br /><br> Change from baseline in ALSFRS-R scores<br /><br>* Change from baseline in percent of predicted slow vital capacity<br /><br>* Change from baseline in muscle strength, as measured by hand-held dynamometry<br /><br>* Change from baseline in bulbar strength, as measured by the Iowa Oral<br /><br>Pressure Instrument</p><br>