A Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB078 in Adults With C9ORF72-Associated Amyotrophic Lateral Sclerosis

• ClinicalTrials.gov Identifier: NCT03626012
• Recruitment Status: Active, not recruiting
• First Posted: August 10, 2018
• Last Update Posted: October 3, 2019
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Study Description

Brief Summary:

The primary objective of this study is to evaluate the safety and tolerability of BIIB078 in adults with C9ORF72-ALS. The secondary objective of this study is to evaluate the pharmacokinetic profile of BIIB078. As the first-in-human study, the study enrolls a small number of patients in each cohort. Every patient in a cohort is treated with the same dose or placebo. The study is designed to evaluate and confirm the safety of each dose before enrolling and exposing new patients to a higher dose in the next cohort. Therefore, proceeding from cohort to cohort, the recruitment status of "Active, not recruiting" may change. Please contact clinicaltrials@biogen.com for further information

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: BIIB078; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: September 10, 2018
• Estimated Primary Completion Date: September 27, 2021
• Estimated Study Completion Date: September 27, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1: BIIB078 First Dosage; BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.	Drug: BIIB078; Administered as specified in the treatment arm.
Experimental: Cohort 2: BIIB078 Second Dosage; BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.	Drug: BIIB078; Administered as specified in the treatment arm.
Experimental: Cohort 3: BIIB078 Third Dosage; BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.	Drug: BIIB078; Administered as specified in the treatment arm.
Experimental: Cohort 4: BIIB078 Fourth Dosage; BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.	Drug: BIIB078; Administered as specified in the treatment arm.
Experimental: Cohort 5: BIIB078 Fifth Dosage; BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.	Drug: BIIB078; Administered as specified in the treatment arm.
Experimental: Cohort 6: BIIB078 Sixth Dosage; BIIB078 will be administered as a loading regimen of 3 doses, on Day 1 and two later days, followed by two maintenance doses on two later days.	Drug: BIIB078; Administered as specified in the treatment arm.
Placebo Comparator: Cohorts 1-6: Placebo; Matching placebo will be administered as a loading regimen of 3 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.

Outcome Measures

Primary Outcome Measures :

1. Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline through End of Study (Approximately Day 239) ]
   An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, places participant at immediate risk of death, requires initial or prolonged inpatient hospitalization, results in persistent or significant disability/incapacity, results in congenital anomaly, is a medically important event.

Secondary Outcome Measures :

1. Serum BIIB078 Concentration [ Time Frame: Baseline and at multiple time points up to Day 176 ]
2. Area Under the Concentration-Time Curve (AUC) from Time 0 to Infinity (AUCinf) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
3. AUC from Time 0 to Time of the Last Measurable Concentration (AUClast) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
4. Maximum Observed Concentration (Cmax) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
5. Time to Reach Cmax (Tmax) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
6. Terminal Elimination Half-Life (t 1/2) [ Time Frame: Baseline and at multiple time points up to Day 176 ]

Eligibility Criteria

• 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 subject 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 subject privacy regulations; or, in the event of the subject'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 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.
• 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).
• 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 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 subject as to be able to provide accurate information about the subject's cognitive and functional abilities at Screening.

Key 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.
• 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 anti-platelet or anticoagulant therapy ≤ 14 days before Screening (with the exception of aspirin ≤ 325 mg/day) or anticipated use during the study.
• Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system during the study period.
• Female subjects who are pregnant or currently breastfeeding.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

United States, California

Research Site

La Jolla, California, United States, 92037

Research Site

Los Angeles, California, United States, 90048

Research Site

Palo Alto, California, United States, 94303

United States, Florida

Research Site

Jacksonville, Florida, United States, 32224

Research Site

Miami, Florida, United States, 33136

United States, Georgia

Research Site

Atlanta, Georgia, United States, 30322

United States, Maryland

Research Site

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Research Site

Boston, Massachusetts, United States, 02114

United States, Missouri

Research Site

Saint Louis, Missouri, United States, 63110

United States, Nebraska

Research Site

Lincoln, Nebraska, United States, 68506-2960

United States, New York

Research Site

New York, New York, United States, 10032

United States, Tennessee

Research Site

Knoxville, Tennessee, United States, 37920

Canada, Quebec

Research Site

Montreal, Quebec, Canada, H3A 2B4

Netherlands

Research Site

Utrecht, Netherlands, 3508 GA

Research Site

Utrecht, Netherlands, 3584 CX

United Kingdom

Research Site

London, United Kingdom, SE5 9RS

Research Site

Sheffield, United Kingdom, S10 2HQ

Sponsors and Collaborators

Biogen

Investigators

• Study Director: Medical Director; Biogen

More Information

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT03626012 History of Changes
• Other Study ID Numbers: 245AS101; 2017-000294-36 ( EudraCT Number )
• First Posted: August 10, 2018
• Last Update Posted: October 3, 2019
• Last Verified: September 2019

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

Additional relevant MeSH terms:

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