This is an interventional clinical trial which involves individuals with ALS and a known SOD1 genetic mutation. The trial intends to add to medical knowledge by evaluating the safety, tolerability and pharmacokinetics (PKs) of BIIB067 as an investigational therapy.
Pharmacokinetics looks at the level of the investigational therapy in the body and what happens to this level from the time that it is given to the time that it is eliminated from the body.
The investigational therapy is delivered five times during the treatment period and an overnight stay is required in hospital following administration of the first dose.
Participation lasts approximately 31 weeks, and includes:
• A screening period (1-3 visits)
• A treatment / placebo period (5 visits to receive doses of the investigational therapy)
• A follow-up period (8 visits and approximately 10 telephone calls)
Participants will be randomly assigned (by chance) to receive either the investigational therapy or placebo (an inactive substance). Three out of every four participants will receive the investigational therapy, and one out of every four participants will receive the placebo. The clinical trial is “double blind,” which means that neither you nor the study doctor (and his/her staff) will know which one you have been assigned to receive.
|Study title||Single and Multiple Dose Study of BIIB067 in Adults With Amyotrophic Lateral Sclerosis (ALS)|
|UK Chief Investigator||Professor Dame Pamela Shaw|
|Research summary||Amyotrophic lateral sclerosis (ALS), is a rapidly progressive, invariably fatal neurological disease that attacks the nerve cells (neurons) responsible for controlling voluntary muscles (muscle action we are able to control, such as those in the arms, legs, and face).
Although the majority of patients suffer from sporadic ALS (without family history), approximately 2%, have an inherited, or familial, form of ALS caused by a variety of genetic mutations known as superoxide dismutase 1 mutations (SOD1-ALS).
BIIB067 is an investigational drug which reduces the levels of the toxic protein that causes the genetic mutation. The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of BIIB067, in adults with SOD1-ALS.
The study is randomised (participants are randomly allocated to treatment), double-blind (neither the participant nor study team will know which treatment is being given) and placebo-controlled (the study drug will be compared with an inactive “placebo”). It consists of 2-parts, A (single ascending dose) and B (multiple ascending dose) and BIIB067 will be administered by intrathecal bolus injection (via an injection into the spinal canal) to up to approximately 72 adults with either sporadic ALS (Part A only) or SOD1-ALS (Parts A and B).
Approximately 17 sites are planned in the United States, Canada, and Western Europe.
This study is sponsored by Biogen Idec Research Limited.
|Inclusion/exclusion criteria||Key Inclusion Criteria:
- Weakness attributable to ALS and documented SOD1 mutation at Screening Visit 2.
- A forced vital capacity (FVC) ≥50% of predicted value as adjusted for sex, age, and height (from the sitting position). Participants with stable FVC <50% but ≥45%, whose FVC has not declined by more than 5% in the last 6 months may be considered for inclusion, at the discretion of the Investigator.
- 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.
- 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.
Key Exclusion Criteria:
- History of or positive test result for human immunodeficiency virus.
- History of, or positive test result at Screening, for hepatitis C virus antibody.
- 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.
- Treatment with another investigational drug, biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering ribonucleic acid, stem cell therapy, or gene therapy is allowed.
- 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 or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system (DPS) during the study period.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
|Current status||Active – recruiting|
|Contact details||If you think you might be interested please contact Neurologist Professor Christopher McDermott via the study nurse on 0114 2222264 or email@example.com|
|Recruitment group(s)||Patients with MND|
|Recruitment target(s)||84 participants worldwide|
|Key dates||Study start date: 31 January 2016 (global)
Target study completion date: 02 February 2019 (global)
|Study design||Interventional (clinical trial)|
|Intervention (if applicable)||Drug: BIIB067
|Phase (if applicable)||Phase 1 (first-in-human)|
|Outcome measures||Primary Outcome Measures:
- Number of participants experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Number of participants with clinically significant laboratory assessment abnormalities
- Number of participants with clinically significant vital sign abnormalities
- Number of participants with clinically significant physical examination abnormalities
- Number of participants with clinically significant neurological examination abnormalities
- Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities
- PK parameter of BIIB067 in plasma: Maximum observed concentration (Cmax)
- PK parameter of BIIB067 in plasma: Time to reach maximum observed concentration (Tmax)
- PK parameter of BIIB067 in plasma: Area under the concentration-time curve from time zero to infinity (AUCinf)
- PK parameter of BIIB067 in plasma: Area under the concentration-time curve from time zero to the time of the last measurable concentration (AUClast)
- PK parameter of BIIB067 in plasma: Apparent terminal elimination half-life (t1/2)
- PK parameters of BIIB067 in CSF levels: Terminal elimination half-life (t1/2)
Secondary Outcome Measures:
- Change from baseline in CSF levels of SOD1 protein. [ Time Frame: up to day 169 ]
Part A: up to day 57; Part B: up to day 169
|Publications / Results reports|
|Participant Information Sheet|