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

Withdrawn

Conditions: Amyotrophic lateral sclerosis
neurodegenerative disease
10029317

Registration Number: NL-OMON46750

Lead Sponsor: Biogen

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 3

Inclusion Criteria

1. Ability of the subject or his/her legally authorized representative (e.g., spouse) to
understand the purpose and risks of the study, and provide signed and dated informed
consent and authorization to use confidential health information in accordance with
national and local subject privacy regulations.
2. Age >= 18 years old at the time of informed consent.
3. All subjects 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. In addition, subjects should not donate
sperm or eggs for the duration of the study and for at least 5 months after their last dose
of study treatment.
4. 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.
5. Slow vital capacity (SVC) >= 50% of predicted value as adjusted for sex, age, and height (from the sitting position).
6. Subjects 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). Subjects taking concomitant riluzole must be willing to continue with the same dose regimen throughout the study, unless the Investigator determines that riluzole should be discontinued for medical reasons, in which case it may not be restarted during the study.
7. Subjects 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). Subjects 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.
8. ALS Cognitive Behavioral Screen (ALS-CBS) score >= 11 for the cognitive portion;
>= 33 for the behavioral portion.
9. 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.
10. 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. Coagulation tests may be repeated once at the
local laboratory if, in the opinion of the Investigator, values of the initial tests are out of
range but not clinically significant. Subjects with nonclinically significant and stable
out-of-range values may be eligible to enroll in the study at the discretion of the
Investigator, and after a consultation with the Sponsor.
11. Has an informant/caregiver who, in the Investigator*s judgment, has frequent and
sufficient contact with the subject as to be able to provide accurate information about the
subject*s cognitive and functional abilities at Screening. An informant/caregiver should
be available at Screening, and the participation of the informant/caregiver for the duration of the study is encouraged.

Exclusion Criteria

Medical History
1. History of drug abuse or alcoholism <= 6 months of Screening that would limit
participation in the study, as determined by the Investigator.
2. Tracheostomy.
3. History of a deep venous thrombosis or pulmonary embolism since the date of ALS
diagnosis or <= 2 years of Screening, whichever duration is greater.
4. Ongoing medical condition (e.g., wasting or cachexia, severe anemia) that would, in the opinion of the Investigator, interfere with the conduct or assessments of the study.
5. Significant cognitive impairment or unstable psychiatric illness, including psychosis,
suicidal ideation, suicide attempt, or untreated major depression <= 90 days of Screening,
which in the opinion of the Investigator would interfere with the study procedures.
6. History of allergies to substances that will be used for the LP (e.g., anesthetics, if used per institutional practice).
7. Presence of risk of bleeding that could place a subject at an increased risk for
intraoperative or postoperative bleeding. These could include, but are not limited to,
anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand*s disease, liver disease).
8. Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter.
9. Presence of an implanted intravenous port/catheter.
10. Clinically significant abnormalities in hematology or blood chemistry parameters, as
determined by the Investigator, which would render the subject unsuitable for enrollment.
11. Clinically significant, as determined by the Investigator, 12-lead electrocardiogram
(ECG) abnormalities, including corrected QT interval using Fridericia*s correction
method of >450 ms for males and >470 ms for females.
12. Alanine aminotransferase , aspartate aminotransferase , or total bilirubin levels >= 2 times the upper limit of normal. Patients with previously established Gilbert*s syndrome and elevated levels of bilirubin consistent with such syndrome are allowed in the study.
Infections
13. History of or positive test result at Screening for human immunodeficiency virus. The
requirement for testing at Screening may be omitted if it is not permitted by local
regulations.
14. History of, or positive test result at Screening for, hepatitis C virus antibody.
15. Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]). Subjects with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive hepatitis B surface
antibody immunoglobulin G, and positive HBcAb) or vaccination (defined as positive
hepatitis B surface antibody [HBsAb]) are eligible to participate in the study.
16. Presence of an untreated or inadequately treated active infection requiring systemic
antiviral or antimicrobial therapy at any time during the screening period.
Medications
17. Treatment with another investigational drug (including investigational drugs for ALS
through compassionate use programs) or biological agent within 1 month of Screening or 5 half-lives of study agent, whichever is longer.
18. Treatment with antiplatelet or anticoagulant therapy <= 14 days before Screening (with the excepti

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Incidence of adverse and serious adverse events.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Serum BIIB078 concentration<br /><br>- Serum PK parameters:<br /><br>- Area under the concentration-time curve (AUC) from time 0 to infinity (AUC)<br /><br>- AUC from time 0 to time of the last measurable concentration (AUClast)<br /><br>- Maximum observed concentration (Cmax)<br /><br>- Time to reach Cmax (Tmax)<br /><br>- Terminal elimination half-life (t)</p><br>