Amyotrophic Lateral Sclerosis
Conditions
Brief summary
This is a Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RAG-17 in Subjects with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) Gene Mutation
Detailed description
The study is a phase 1, randomized, double-blind, placebo controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RAG-17 in patients with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) gene mutation. The dose levels will be evaluated sequentially across separate cohorts using a rules-based design, wherein participants will receive RAG-17 or placebo at a ratio of 3:1.
Interventions
DRUGRAG-17
RAG-17 is a therapeutic small interfering RNA (siRNA).
DRUGPlacebo
Placebo will be administered via intrathecal injection
Sponsors
Ractigen Therapeutics.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntarily consents to participate in this study and provides written informed consent prior to the start of any study specific procedures. 2. ≥ 18 years of age at the time of informed consent. 3. Diagnosis of possible, laboratory supported probable, probable, or definite ALS according to the World Federation of Neurology El Escorial. 4. Documented SOD1 mutation. 5. Forced vital capacity (FVC) ≥50% of predicted value as adjusted for sex, age, and height (measured seated). 6. If taking riluzole or edaravone, subject must be on a stable dose or ≥30 days prior to Day 1 and expected to remain at that dose until the final study visit.
Exclusion criteria
1. Documented p.F21C SOD1 mutation. 2. 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. 3. Current enrollment in any other interventional study. 4. History of or positive test result for human immunodeficiency virus, hepatitis C virus antibody or hepatitis B virus. 5. Pregnant or currently breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events(AEs) | Before treatment and within 57 days after treatment | Assesment of Safety and Tolerability: Incidence and severity of treatment-emergent Adverse Events(AEs) and Serious Adverse Events(SAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Pharmacokinetic (PK) Parameter: AUC0-inf | Before treatment and within 48 hours after treatment | Area Under the Plasma Concentration-Time Curve from Time 0 Extrapolated to Infinity |
| Plasma Pharmacokinetic (PK) Parameter: Cmax | Before treatment and within 48 hours after treatment | Peak Plasma Concentration |
| Plasma Pharmacokinetic (PK) Parameter: Tmax | Before treatment and within 48 hours after treatment | Time to reach Cmax. If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value |
| Plasma Pharmacokinetic (PK) Parameter: λz | Before treatment and within 48 hours after treatment | Elimination Rate Constant |
| Plasma Pharmacokinetic (PK) Parameter: T½ | Before treatment and within 48 hours after treatment | Apparent Terminal Elimination Half-life of Study Drug |
| Plasma Pharmacokinetic (PK) Parameter: AUC0-last | Before treatment and within 48 hours after treatment | Area Under the Plasma Concentration-Time Curve from Time 0 to the Last Measurable Non-zero Concentration |
| Plasma Pharmacokinetic (PK) Parameter: Vz/F | Before treatment and within 48 hours after treatment | Apparent Volume of Distribution |
| Plasma Pharmacokinetic (PK) Parameter: MRT | Before treatment and within 48 hours after treatment | Mean Residence Time |
| CSF Pharmacokinetic (PK) Parameter: Concentration | Before treatment and within 29 days after treatment | Concentration in Cerebrospinal Fluid(CSF) |
| CSF Pharmacokinetic (PK) Parameter: T½ | Before treatment and within 29 days after treatment | Half-life in Cerebrospinal Fluid(CSF) |
| Plasma Pharmacokinetic (PK) Parameter: CL/F | Before treatment and within 48 hours after treatment | Apparent Clearance |
Countries
China
Contacts
Primary ContactLong-Cheng Li
Outcome results
None listed