Study of Safety, Tolerability, and Biological Activity of LAM-002A in C9ORF72-Associated Amyotrophic Lateral Sclerosis
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT05163886|
Recruitment Status : Recruiting
First Posted : December 20, 2021
Last Update Posted : December 27, 2021
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis ALS||Drug: LAM-002A Other: Placebo||Phase 2|
This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled, biomarker- driven clinical trial to evaluate the safety, tolerability, and biological effect of LAM-002A in adults diagnosed with ALS who are confirmed to carry the Chromosome 9 Open Reading Frame 72 (C9ORF72) gene mutation (C9ALS).
Informed consent will be obtained prior to the conduct of any study-related procedures. Study eligibility will be assessed at the screening visit and during the screening period. Participants must satisfy the inclusion and exclusion criteria for the study.
Participants will receive either standard of care plus LAM-002A or standard of care and placebo (randomized 2:1) for the first 12 weeks of the study (Core Study). LAM-002A will be administered as oral capsules 125 mg BID (250 mg total daily dose). The LAM-002A dose may be reduced to 100 mg BID (200 mg total daily dose) if adverse effects develop.
Participants who complete the first 12 weeks on treatment will be eligible to receive active drug (LAM-002A capsules at maximum tolerated dose of 125 or 100 mg BID) for the remainder of the study [Open Label Extension (OLE)] up to Week 24, with a Week 28 telephone phone call planned 28 days after the last dose of study drug. After the start of treatment on Week 1, participants will be followed at Weeks 2, 4, 8, 12, 16, 20, 24, and 28. Participants can withdraw from the study at any time.
The study will employ an interim analysis by an independent Data Safety Monitoring Board (DSMB) for safety and clinical efficacy. The DSMB will be responsible for reviewing the interim safety and futility analyses and recommending study continuation, termination, or study design adaptation.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Double-blind, placebo-controlled|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase IIa Trial to Evaluate the Safety, Tolerability, and Biological Activity of LAM-002A (Apilimod Dimesylate Capsules) in C9ORF72-Associated Amyotrophic Lateral Sclerosis|
|Estimated Study Start Date :||December 23, 2021|
|Estimated Primary Completion Date :||September 16, 2022|
|Estimated Study Completion Date :||September 16, 2022|
LAM-002A will be administered orally in five 25 mg capsules twice a day (250 mg total daily dose).
LAM-002A (apilimod dimesylate) is formulated in capsules containing 25 mg of apilimod dimesylate. The capsule is Swedish orange, size 0.
Placebo Comparator: Placebo
Placebo matching LAM-002A will be administered orally in 5 capsules twice a day.
Microcrystalline cellulose in Swedish orange, size 0 capsules.
- Safety of LAM-002A: occurrence of TEAEs [ Time Frame: 28 Weeks ]The occurrence of serious and non-serious treatment-emergent adverse events (TEAEs) and clinically significant treatment-emergent abnormalities in clinical and laboratory values.
- Tolerability of LAM-002A: completion of core study treatment [ Time Frame: 12 Weeks ]The percentage of participants who complete 12 weeks on study treatment during the Core Study.
- Plasma Pharmacokinetics of LAM-002A [ Time Frame: 24 Weeks ]The levels of LAM-002 and metabolites in plasma levels.
- CSF Pharmacokinetics of LAM-002A [ Time Frame: 24 Weeks ]The levels of LAM-002 and metabolites in cerebral spinal fluid (CSF) levels.
- Changes in biomarkers [ Time Frame: 24 Weeks ]Changes in plasma and CSF levels of a LAM-002A-induced biomarker.
- Tolerability of LAM-002A: completion of open-label study treatment [ Time Frame: 12 Weeks ]Secondary measures of tolerability will consider completion of 12 weeks on open-label study treatment during the OLE.
- Changes in ALSFRS-R [ Time Frame: 28 Weeks ]Change in Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) total and domain scores. Score ranges from 0-48 with the higher the score indicating better function.
- Changes in Vital Capacity [ Time Frame: 24 Weeks ]Change in vital capacity (VC).
- Permanent assisted ventilation-free survival [ Time Frame: 24 Weeks ]Change in percent of ventilation-free survival summaries.
- Changes in ALS-CBS [ Time Frame: 24 Weeks ]Change in Amyotrophic Lateral Sclerosis Cognitive Behavioral Scale (ALS-CBS). Comprised of two sub-scores. The cognitive sub-score is rated 0-20 with the higher the score the better patient cognitive function. The caregiver sub-score is rated 0-45 with the higher the score the better patient cognitive function as assessed by their caregiver.
- Exploratory biomarkers [ Time Frame: 24 Weeks ]Analysis of exploratory disease related biomarkers.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05163886
|Contact: Femi Okubanjo, B.Pharm, CSMfirstname.lastname@example.org|
|United States, Florida|
|Holy Cross Hospital||Not yet recruiting|
|Fort Lauderdale, Florida, United States, 33308|
|United States, Iowa|
|University of Iowa Hospitals and Clinics||Not yet recruiting|
|Iowa City, Iowa, United States, 52242|
|United States, Maryland|
|Johns Hopkins University School of Medicine||Not yet recruiting|
|Baltimore, Maryland, United States, 21205|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Katherine Nicholson, M.D.||Massachusetts General Hospital|