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Long-Term Evaluation of BIIB067

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ClinicalTrials.gov Identifier: NCT03070119
Recruitment Status : Enrolling by invitation
First Posted : March 3, 2017
Last Update Posted : March 26, 2019
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Biogen

Brief Summary:
The primary objective of the study is to evaluate the long-term safety and tolerability of BIIB067 in participants with amyotrophic lateral sclerosis (ALS) and confirmed superoxide dismutase 1 (SOD1) mutation. The secondary objectives are to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles and effects on disease progression of BIIB067 administered to participants with ALS and confirmed SOD1 mutation.

Condition or disease Intervention/treatment Phase
ALS Caused by Superoxide Dismutase 1 (SOD1) Mutation Drug: BIIB067 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Extension Study to Assess the Long-Term Safety, Tolerability, Pharmacokinetics, and Effect on Disease Progression of BIIB067 Administered to Previously Treated Adults With Amyotrophic Lateral Sclerosis Caused by Superoxide Dismutase 1 Mutation
Actual Study Start Date : March 8, 2017
Estimated Primary Completion Date : February 26, 2021
Estimated Study Completion Date : February 26, 2021


Arm Intervention/treatment
Experimental: BIIB067
Participants who have completed Parts A, B, or C of study 233AS101 will be placed in this arm.
Drug: BIIB067
Participants will receive a loading dose regimen followed by maintenance dosing.




Primary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 248 ]
    An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.


Secondary Outcome Measures :
  1. PK Parameter of BIIB067 in Plasma: Maximum Observed Concentration (Cmax) [ Time Frame: Up to Week 248 ]
  2. PK Parameter of BIIB067 in Plasma: Time to Reach Maximum Observed Concentration (Tmax) [ Time Frame: Up to Week 248 ]
  3. PK Parameter of BIIB067 in Plasma: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUCinf) [ Time Frame: Up to Week 248 ]
  4. PK Parameter of BIIB067 in Plasma: Area Under the Concentration-Time Curve from Time 0 to Time of the Last Measurable Concentration (AUClast) [ Time Frame: Up to Week 248 ]
  5. PK Parameter of BIIB067 in Plasma: Apparent Terminal Elimination Half-Life (t½) [ Time Frame: Up to Week 248 ]
  6. PK Parameter of BIIB067 in CSF: t½ [ Time Frame: Up to Week 248 ]
  7. Change from Baseline in ALS Functional Rating Scale - Revised (ALSFRS-R) Score [ Time Frame: Up to Week 248 ]
    The ALSFRS-R measures 4 functional domains, including respiratory, bulbar function, gross motor skills, and fine motor skills. There are 12 questions, each scored from 0 to 4, for a total possible score of 48, with higher scores representing better function

  8. Change from Baseline in Slow Vital Capacity (SVC) [ Time Frame: Up to Week 248 ]
    Vital capacity will be measured by means of an SVC test, administered in the upright position. Upright SVC will be determined by performing 3 to 5 measures, in accordance with criteria established by the American Thoracic Society and the European Respiratory Society.

  9. Change from Baseline in Handheld Dynamometry (HHD) Score [ Time Frame: Up to Week 248 ]
    Quantitative muscle strength will be evaluated using 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.

  10. Overall Survival [ Time Frame: Up to Week 248 ]
    Overall survival is defined as the time from randomization until death due to any cause.

  11. Ventilation Assistance-Free Survival (VAFS) [ Time Frame: Up to Week 248 ]

    VAFS is defined as the time to the earliest occurrence of one of the following events: death, first use of noninvasive ventilation (NIV) for ≥22 hours per day for

    • 10 consecutive days, first use of permanent assisted ventilation (PAV) for ≥22 hours per day for
    • 7 consecutive days.

  12. PD Parameter of BIIB067 in CSF: Change from Baseline in Total SOD1 [ Time Frame: Up to Week 248 ]
  13. PD Parameter of BIIB067 in CSF: Change from Baseline in Total Phosphorylated Axonal Neurofilament Heavy Chain (p-NHF) [ Time Frame: Up to Week 248 ]
  14. PD Parameter of BIIB067 in Plasma: Change from Baseline in Total p-NFH [ Time Frame: Up to Week 248 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Must have diagnosis of SOD1-ALS, and must have completed the End of Study Visit for either Parts A, B, or C of Study 233AS101 (NCT02623699) (i.e., were not withdrawn).
  • If taking riluzole, must be receiving a stable dose for ≥30 days prior to Day 1 and expected to remain at that dose until the final study visit.
  • For participants of childbearing potential must agree to practice effective contraception during the study and be willing and able to continue contraception for 5 months after their last dose of study treatment.
  • 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.
  • Participants from Study 233AS101 Parts A and B must have a washout ≥16 weeks between the last dose of study treatment received in Study 233AS101 and the first dose of BIIB067 received in the current Study 233AS102.
  • If taking edaravone, participant must have initiated edaravone ≥60 days (2 treatment cycles) prior to Day 1. Edaravone may not be administered on dosing days during this study.

Key Exclusion Criteria:

  • History of allergies to a broad range of anesthetics.
  • 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 bleeding during or after a Lumbar Puncture (LP) procedure. These risks 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 of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter.
  • Prior or current treatment with small interfering ribonucleic acid (RNA), stem cell therapy, or gene therapy.
  • Treatment with another investigational drug, biological agent (excluding BIIB067), or device within 1 month or 5 half-lives of study agent, whichever is longer.
  • Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system (DPS) during the study period.
  • Female participants who are pregnant or currently breastfeeding.
  • Current enrollment in any other interventional study.
  • Current or recent (within 1 month) use, or anticipated need, in the opinion of the Investigator, of copper (II) (diacetyl-bis(N4-methylthiosemicarbazone)) or pyrimethamine.
  • Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]). Participants 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 anti-HBs) are eligible to participate in the study.
  • Presence of an implanted intravenous port/catheter.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03070119


Locations
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United States, Arizona
Barrow Neurological Institute
Phoenix, Arizona, United States, 85013
United States, California
University of California San Diego Medical Center
La Jolla, California, United States, 92093-0949
California Pacific Medical Center
San Francisco, California, United States, 94118
United States, Florida
Bioclinica Orlando
Orlando, Florida, United States, 32806
United States, Georgia
The Emory Clinic
Atlanta, Georgia, United States, 30322
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospita
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, Tennessee
New Orleans Center for Clinical Research
Knoxville, Tennessee, United States, 37920
Belgium
UZ Leuven
Leuven, Belgium, 3000
Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Montreal Neurological Institute Clinical Research Unit
Montreal, Quebec, Canada, H3A2B4
Germany
Universitaetsklinikum Ulm
Ulm, Baden Wuerttemberg, Germany, 89081
United Kingdom
Sheffield Institute for Translational Neuroscience
Sheffield, South Yorkshire, United Kingdom, S102HQ
Sponsors and Collaborators
Biogen
Ionis Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Director Biogen

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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT03070119     History of Changes
Other Study ID Numbers: 233AS102
2016-003225-41 ( EudraCT Number )
First Posted: March 3, 2017    Key Record Dates
Last Update Posted: March 26, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Amyotrophic Lateral Sclerosis
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Superoxide Dismutase
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs