Study of Safety, Tolerability, and Biological Activity of LAM-002A in C9ORF72-Associated Amyotrophic Lateral Sclerosis
- Conditions
- Amyotrophic Lateral SclerosisALS
- Registration Number
- NCT05163886
- Lead Sponsor
- OrphAI Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br> 1. Diagnosis of C9ORF72-associated ALS with BOTH of the following:<br><br> 1. Documentation of a clinical genetic test demonstrating the presence of a<br> pathogenic repeat expansion in C9ORF72. If there is a strong clinical suspicion<br> for C9ALS based on C9-positive family history and El Escorial Criteria<br> consistent with a diagnosis of ALS, clinical testing for the C9ORF72 repeat<br> expansion may be performed with study screening labs at the discretion of the<br> Site Investigator (SI), medical monitor, and study sponsor.<br><br> AND<br><br> 2. Must meet possible, laboratory-supported probable, probable, or definite<br> criteria for diagnosing ALS by revised El Escorial criteria (Brooks 2000).<br><br> 2. Age 18 or older<br><br> 3. Capable of providing informed consent at the Screening Visit and complying with<br> study procedures throughout the study, in the SI's opinion, and at the discretion of<br> the medical monitor and study sponsor.<br><br> 4. In the case that a participant lacks the ability to provide informed consent.<br> Informed consent will be sought from the participant's surrogate representative.<br><br> 5. Able to safely swallow study drug capsule at screening and throughout study. May use<br> thickened substances to assist in swallowing drug.<br><br> 6. Vital Capacity greater than and equal to 50% of predicted at the time of the<br> Screening Visit measured by Slow Vital Capacity (SVC), or, if required due to<br> COVID-19 pandemic-related restrictions and with Sponsor approval, Forced Vital<br> Capacity (FVC) measured in-person or via telemedicine.<br><br> 7. Participants must either not take or be on a stable dose of riluzole (as either a<br> tablet or oral suspension) for greater than 30 days prior to the Screening Visit.<br> Riluzole-naïve participants are permitted in the study.<br><br> 8. Participants must either not take edaravone or have completed at least one 14-day<br> cycle with plan for continuation of edaravone prior to the Screening Visit.<br> Participants must be off cycle and at least 2 days after the last dose<br> administration of edaravone at the time of study visit. Edaravone-naïve participants<br> are permitted in the study.<br><br> 9. Participants must be able to complete all study procedures, including the lumbar<br> punctures (LP) at the time of the Screening Visit, in the SI's opinion.<br><br> 10. Geographically accessible to the site.<br><br>Exclusion Criteria:<br><br> 1. Clinically significant unstable medical condition (other than ALS) that would pose a<br> risk to the participant, according to the SI's judgment [e.g., cardiovascular<br> instability, systemic infection, or clinically significant laboratory abnormality or<br> electrocardiogram (ECG) changes].<br><br> 1. Gastrointestinal disease (e.g., gastric, or intestinal bypass surgery,<br> jejunostomy tube, pancreatic enzyme insufficiency, malabsorption syndrome,<br> symptomatic inflammatory bowel disease, chronic diarrheal illness, bowel<br> obstruction) that might interfere with drug absorption or with interpretation<br> of gastrointestinal AEs. Gastrostomy tube placement is allowed prophylactically<br> or to supplement nutrition/hydration but may not be used for study drug<br> administration.<br><br> 2. Hepatic profile showing any of the following:<br><br> i. Serum alanine aminotransferase (ALT) greater than 5 × upper limit of normal<br> (ULN).<br><br> ii. Serum aspartate aminotransferase (AST) greater than 5 × ULN.<br><br> iii. Serum bilirubin greater than 1.5 × ULN.<br><br> c. Renal profile showing an estimated creatinine clearance (eClCR) less than 30<br> mL/minute (with eClCR to be calculated by the method at the laboratory performing<br> the serum creatinine test).<br><br> 2. Presence of a neurodegenerative cognitive or motor syndrome (e.g., Alzheimer's<br> disease, Parkinson's disease) not related to the C9ORF72 repeat expansion.<br><br> 3. Presence of unstable psychiatric disease or substance abuse that would impair<br> ability of the participant to provide informed consent, in the SI's opinion.<br><br> 4. Active cancer or history of cancer, except for the following: basal cell carcinoma<br> or successfully treated squamous cell carcinoma of the skin, cervical carcinoma in<br> situ, prostatic carcinoma in situ, or other malignancies curatively treated and with<br> no evidence of disease recurrence for at least 3 years. Active cancer includes<br> cancers with current disease manifestations or therapy that could adversely affect<br> subject safety and longevity, create the potential for drug-drug interactions, or<br> compromise the interpretation of study results.<br><br> 5. Prior solid organ transplantation.<br><br> 6. Ongoing immunosuppressive therapy including systemic or enteric corticosteroids at<br> screening or for the duration of the trial, at the discretion of the site<br> investigator and medical monitor.<br><br> 7. Use within 5 days prior to randomization or for the duration of the trial of a<br> strong inhibitor or inducer of cytochrome P450 (CYP) 3A4 or expected requirement for<br> chronic use of a strong inhibitor or inducer of CYP3A4 during study therapy.<br><br> 8. Use within 5 days prior to randomization or for the duration of the trial of drug<br> that is a moderate-to-strong substrate of CYP2C9 (including warfarin, tolbutamide,<br> phenytoin, glimepiride) or expected requirement for chronic use of such drugs during<br> study therapy, at the discretion of the site investigator and medical monitor.<br><br> 9. Use of investigational treatments for ALS (off-label use or active participation in<br> a clinical trial) within 5 half-lives (if known) or 30 days (whichever is longer)<br> prior to the Screening Visit.<br><br> 10. Exposure at any time to any gene therapies under investigation for the treatment of<br> ALS (off-label use or investigational).<br><br> 11. If female, breastfeeding, known to be pregnant, planning to become pregnant during<br> the study, or of child-bearing potential and unwilling to use effective<br> contraception for the duration of the trial and for 3 months after discontinuing<br> treatment.<br><br> 12. If male of reproductive capacity, unwilling to use effective contraception for the<br> duration of the trial and for 3 months after discontinuing study treatment.<br><br> 13. Anything that would place the participant at increased risk or preclude the<br> participant's full compliance with or completion of the study, in the SI's opinion.<br><br> 14. If a participant is being re-screened, the disqualifying condition has not been<br> resolved, or the mandatory wash-out duration has not occurred.<br><br> 15. Contraindication to undergoing a lumbar puncture (LP) in the SI's opinion.<br> Participants undergoing the LP must not be currently taking anticoagulation and<br> antiplatelet medications such as warfarin and clopidogrel bisulfate (Plavix™), that<br> would be a contraindication to LP; aspirin and non-steroidal anti-inflammatories are<br> allowed.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety of LAM-002A: occurrence of TEAEs;Tolerability of LAM-002A: completion of core study treatment;Plasma Pharmacokinetics of LAM-002A;CSF Pharmacokinetics of LAM-002A
- Secondary Outcome Measures
Name Time Method Changes in biomarkers;Tolerability of LAM-002A: completion of open-label study treatment