Primary objective: To stu dy the safety and tolerability of BIIB078 in adults with C9ORF72-ALS.Secondary objective: To evaluate the pharmacokinetics (PK) profile of BIIB078 and to evaluate the effects of BIIB078 on clinical function.
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Number of Participants with adverse and serious adverse events.
Secondary outcome
* Serum BIIB078 concentrations
* Serum PK parameters:
* Area under the concentration-time curve (AUC) from time 0 to infinity
* AUC from time 0 to time of the last measurable concentration
* Maximum observed concentration (Cmax)
* Time to reach Cmax
* Terminal elimination half-life (t*)
An additional secondary objective is to evaluate the effects of BIIB078 on
clinical function.
The additional secondary endpoints that relate to this objective are as follows:
* Change from baseline in ALSFRS-R scores
* Change from baseline in percent of predicted slow vital capacity
* Change from baseline in muscle strength, as measured by hand-held dynamometry
* Change from baseline in bulbar strength, as measured by the Iowa Oral
Pressure Instrument
Background summary
Amyotrophic lateral sclerosi s is a disease that causes motor nerve cells to
gradually break down and die. In most patients, the cause of ALS is not known,
and doctors describe patients in this group as *sporadic ALS* patients. In a
separate small group of ALS patients (C9ORF72 ALS patients), the disease is
caused by a genetic mutation in the C9ORF72 gene. The mutation of the C9ORF72
gene leads to the production of abnormal C9ORF72 gene products that are likely
to be toxic to cells and could possibly lead to nerve cell death.
Study objective
Primary objective: To stu dy the safety and tolerability of BIIB078 in adults
with C9ORF72-ALS.
Secondary objective: To evaluate the pharmacokinetics (PK) profile of BIIB078
and to evaluate the effects of BIIB078 on clinical function.
Study design
This is a Phase 1, randomized, double-blind, placebo-controlled, MAD evaluation
of the safety, tolerability, and PK of BIIB078, administered via an lumbar
puncture to approximately 72 subjects with C9ORF72-ALS. Up to 6 dose levels of
BIIB078 will be administered 5 times, over approximately 3 months for cohorts 1
through 3, and up to 8 times over approximately 6 months for Cohorts 4, 5 and
6.
Intervention
Subjects within each of the 5 cohorts will be randomized in a 3:1
(active:placebo) ratio overall to receive BIIB078 or placebo. The first
dose level was administered to 8 subjects (6 active and 2 placebo).
Dose levels 2 and 3 were each administered to 12 subjects (9 active and
3 placebo). The fourth and fifth dose levels will each be administered to
approximately 20 subjects (15 active and 5 placebo). Subjects who
withdraw may be replaced in a cohort at the discretion of the Sponsor.
The following doses of BIIB078 are planned:
Cohort 1: 5 mg
Cohort 2: 10 mg
Cohort 3: 20 mg
Cohort 4: 35 mg
Cohort 5: 60 mg
Cohort 6: 90 mg
Study burden and risks
Given the severity of the disease and the high unmet medical need in ALS, this
study will be an evaluation of BIIB078 in subjec ts
with C9ORF72-ALS. The proposed MAD study design will minimize the number of
patients who are exposed to sub-therapeutic
doses and/or dosing durations. For each subject, a review of all available
safety and tolerability data will be performed after the first
dose is administered, and subjects will only continue with the multiple dosing
regimen if no safety concerns are noted.
Innovation House, Norden Road 70
Maidenhead Berkshire SL6 4AY
GB
Innovation House, Norden Road 70
Maidenhead Berkshire SL6 4AY
GB
Listed location countries
Age
Inclusion criteria
- Ability of the participant 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 participant privacy regulations; or, in the event of
the participant'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 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 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 of drug abuse or alcoholism * 6 months of Screening that would limit
participation in the study, as determined by the Investigator.
- Tracheostomy.
- Prescreening ALSFRS-R slope less than 0.4 point/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).
- 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 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.
- 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.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-000294-36-NL |
| CCMO | NL69083.000.19 |