A Study to Evaluate the Safety, Tolerability and Metabolism of BIIB105 in Subjects with Amyotrophic Lateral Sclerosis

Overview

About this study

The primary objective is to evaluate the safety and tolerability of BIIB105 in participants with amyotrophic lateral sclerosis (ALS) or poly-CAG expansion (polyQ)-ALS. The secondary objective is to assess the pharmacokinetic (PK) profile of BIIB105 in serum of participants with ALS or poly-CAG expansion (polyQ)-ALS.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Aged 18 years or older at the time of informed consent or participant meets the minimum age of consent in accordance with national regulations (whichever is higher).
  • Ability of the participant and/or his/her legally authorized representative (e.g., parent, spouse, or legal guardian), as appropriate and applicable, to understand the purpose and risks of the study, to provide informed consent, and to authorize the use of confidential 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 superoxide 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 Federation 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 cytosine-adenine-guanine/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 (Day 1).

  • 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 or positive test result at Screening for HIV. The requirement for testing at Screening may be omitted if it is not permitted by local regulations.
  • Current hepatitis C infection (defined as positive HCV antibody and detectable HCV RNA). Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study.
  • Current hepatitis B infection (defined as positive for HBsAg and/or total anti-HBc). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive anti-HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study.
  • 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.
  • Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening Period.
  • History of a deep venous thrombosis or pulmonary embolism ≤ 2 years of Screening, or since the date of ALS diagnosis, whichever is longer.
  • 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.
  • 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.
  • Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression ≤ 90 days of Screening that in the opinion of the Investigator would interfere with the study procedures.
  • History of allergies to anesthetics that will be used for the LP procedure per institutional practice.
  • Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally and could place a participant 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).
  • Presence or anticipated need of an implanted shunt for the drainage of CSF or an implanted CNS catheter at any time during the study.
  • Presence or anticipated need of an implanted intravenous port/catheter at any time during the study.
  • Clinically significant abnormalities in hematology or blood chemistry parameters, as determined by the Investigator that would render the participant unsuitable for enrollment.
  • Clinically significant, as determined by the Investigator, 12-lead ECG abnormalities, including corrected QT interval using Fridericia’s correction method of > 450 msec for males and > 460 msec for females.
  • Prescreening ALSFRS-R slope > -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) in participants from Cohorts A, B, C1, and D1
  • 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 antiplatelet or anticoagulant therapy that cannot safely be interrupted for 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.
  • 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.
  • Inability to comply with study requirements.
  • Other unspecified reasons that, in the opinion of the Investigator or the Sponsor, make the participant unsuitable for enrollment.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Bjorn Oskarsson, M.D.

Contact us for the latest status

Contact information:

Clinical Studies Unit

(904) 953-2255

More information

Publications

Publications are currently not available

Study Results Summary

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Supplemental Study Information

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