|Study 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.|
|UK Chief Investigator||Professor Dame Pamela Shaw|
|Research summary||This is a Phase 1, double blind, multi-centre clinical research study. This means that it is the first time the study drug, BIIB078, will be tested in humans. The main purpose of this study is to find out about the safety, tolerability, and pharmacokinetics (how the study drug is processed by the body) of the study drug when given as repeated doses in adult patients with C9ORF72-associated amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease affecting nerve cells in the brain and spinal cord.
Patients who have been diagnosed with ALS, have the C9ORF72 gene mutation, and are currently showing signs of weakness due to ALS can be invited to be part of this study.
The study drug will be administered “intrathecally”, meaning that the study drug is given to participants by a procedure called a lumbar puncture (LP), using a thin needle that is inserted through the lower back into the fluid-filled space below the end of the spinal cord.
To find out how well the study drug works, it will be compared to placebo. A placebo looks like the study drug but does not contain any active ingredients.
Participants will be assigned to 1 of 4 groups.
• Cohort 1: 5 milligrams (mg) study drug or placebo
• Cohort 2: 20 mg study drug or placebo
• Cohort 3: 60 mg study drug or placebo
• Cohort 4: 120 mg study drug or placebo (this dose level will not be evaluated in the UK)
Participants within each group will be randomised in a 3:1 (active: placebo) ratio overall to receive BIIB078 or placebo.
Approximately 59 participants in about 20 study centres worldwide will take part to ensure approximately 44 participants complete the treatment period. The study will last approximately 40 weeks and participants will visit the study centre up to 13 times.
|Inclusion/exclusion criteria||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 authorised representative (LAR) for the express purpose of having said informed consent and authorisation signed on his/her behalf.
- All participants 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).
- Participants 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).
- 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).
- 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 normalised 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 judgement, 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.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
- History of drug abuse or alcoholism < = 6 months of Screening that would limit participation in the study, as determined by the Investigator.
- History of, or positive test result at Screening for HIV or Hepatitis C.
- Treatment with another investigational drug or biological agent within 1 month of Screening or 5 halflives 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 participants who are pregnant or currently breastfeeding.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
|Current status||Active – recruiting|
King's College Hospital, London
University College London Hospitals NHS Foundation Trust
|Recruitment group(s)||Patients with MND and confirmed presence of a pathogenic mutation in C9ORF72.
|Recruitment target(s)||59 patients globally.|
|Key dates||Actual opening date: 05 August 2019.
Recruitment planned end date: 04 November 2020.
|Funder(s)||Biogen Idec Ltd|
|Sponsor||Biogen Idec Ltd|
|Study design||Interventional, randomised controlled trial|
|Intervention (if applicable)||Drug: BIIB078
|Phase (if applicable)||Phase 1|
|Outcome measures||Primary Outcome Measure:
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:
Serum BIIB078 Concentration [ Time Frame: Baseline and at multiple time points up to Day 176 ]
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 ]
AUC from Time 0 to Time of the Last Measurable Concentration (AUClast) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
Maximum Observed Concentration (Cmax) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
Time to Reach Cmax (Tmax) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
Terminal Elimination Half-Life (t 1/2) [ Time Frame: Baseline and at multiple time points up to Day 176 ]
|Publications / Results reports||Links will be provided when papers are published.|
|Participant Information Sheet|