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A Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB105 in Participants With Amyotrophic Lateral Sclerosis With or Without Poly-cytosine-adenine-guanine (CAG) Expansion in the Ataxin-2 Gene

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ClinicalTrials.gov Identifier: NCT04494256
Recruitment Status : Recruiting
First Posted : July 31, 2020
Last Update Posted : November 13, 2020
Sponsor:
Information provided by (Responsible Party):
Biogen

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: BIIB105 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1 Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB105 Administered Intrathecally to Adults With Amyotrophic Lateral Sclerosis With or Without Poly-CAG Expansion in the Ataxin-2 Gene
Actual Study Start Date : September 28, 2020
Estimated Primary Completion Date : February 28, 2023
Estimated Study Completion Date : February 28, 2023


Arm Intervention/treatment
Experimental: Cohort A
Participants with ALS will receive BIIB105 Dose 1, intrathecally (IT), as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.
Drug: BIIB105
Administered as specified in the treatment arm.

Experimental: Cohort B
Participants with ALS will receive BIIB105 Dose 2, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.
Drug: BIIB105
Administered as specified in the treatment arm.

Experimental: Cohort C1
Participants with ALS will receive BIIB105 Dose 3, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.
Drug: BIIB105
Administered as specified in the treatment arm.

Experimental: Cohort C2
Participants with polyQ-ALS will receive BIIB105 Dose 3, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.
Drug: BIIB105
Administered as specified in the treatment arm.

Experimental: Cohort D1
Participants with ALS will receive BIIB105 Dose 4, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.
Drug: BIIB105
Administered as specified in the treatment arm.

Experimental: Cohort D2
Participants with polyQ-ALS will receive BIIB105 Dose 4, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.
Drug: BIIB105
Administered as specified in the treatment arm.

Placebo Comparator: Cohorts A-D2
Participants with ALS and polyQ-ALS will receive matching placebo to BIIB105 as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.
Drug: Placebo
Administered as specified in the treatment arm.




Primary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Day 175 ]
    An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event.


Secondary Outcome Measures :
  1. Serum Concentration of BIIB105 [ Time Frame: Predose and at multiple timepoints upto 6 hours postdose, from Day 1 up to Day 92 ]
  2. Area Under the Concentration-Time Curve from Time Zero to Infinity (AUCinf) [ Time Frame: Predose and at multiple timepoints upto 6 hours postdose, from Day 1 up to Day 92 ]
  3. Area Under the Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast) [ Time Frame: Predose and at multiple timepoints upto 6 hours postdose, from Day 1 up to Day 92 ]
  4. Maximum Observed Concentration (Cmax) [ Time Frame: Predose and at multiple timepoints upto 6 hours postdose, from Day 1 up to Day 92 ]
  5. Time to Reach Maximum Observed Concentration (Tmax) [ Time Frame: Predose and at multiple timepoints upto 6 hours postdose, from Day 1 up to Day 92 ]
  6. Elimination Half-Life (t1/2) [ Time Frame: Predose and at multiple timepoints upto 6 hours postdose, from Day 1 up to Day 92 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • 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.

Key Exclusion Criteria

  • History or positive test result at Screening for 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.
  • Prescreening Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) slope > -0.4 points/month, where prescreening ALSFRS-R slope is defined as: (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 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.

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): NCT04494256


Contacts
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Contact: US Biogen Clinical Trial Center 866-633-4636 clinicaltrials@biogen.com
Contact: Global Biogen Clinical Trial Center clinicaltrials@biogen.com

Locations
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United States, California
Research Site Recruiting
La Jolla, California, United States, 92093
United States, Georgia
Research Site Recruiting
Atlanta, Georgia, United States, 30322
United States, Maryland
Research Site Recruiting
Baltimore, Maryland, United States, 21218
United States, Missouri
Research Site Recruiting
Saint Louis, Missouri, United States, 63110
United States, Pennsylvania
Research Site Recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen
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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT04494256    
Other Study ID Numbers: 275AS101
2020-000207-36 ( EudraCT Number )
First Posted: July 31, 2020    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/
URL: http://www.biogenclinicaldatarequest.com/

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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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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases