Study of Safety, Tolerability, and Biological Activity of LAM-002A in C9ORF72-Associated Amyotrophic Lateral Sclerosis

NCT05163886 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: LAM-002A-ALS-CLN01
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

Brief Summary

This is a clinical trial to evaluate the safety, tolerability, and biological effect of LAM-002A in adults with C9ORF72-associated ALS (C9ALS).

Conditions

Amyotrophic Lateral Sclerosis; ALS

Keywords

C9ORF72

Outcome Measures

Primary Outcomes (4)

• Safety of LAM-002A: occurrence of TEAEs

  The occurrence of serious and non-serious treatment-emergent adverse events (TEAEs) and clinically significant treatment-emergent abnormalities in clinical and laboratory values.

  28 Weeks

• Tolerability of LAM-002A: completion of core study treatment

  The percentage of participants who complete 12 weeks on study treatment during the Core Study.

  12 Weeks

• Plasma Pharmacokinetics of LAM-002A

  The levels of LAM-002 and metabolites in plasma levels.

  24 Weeks

• CSF Pharmacokinetics of LAM-002A

  The levels of LAM-002 and metabolites in cerebral spinal fluid (CSF) levels.

  24 Weeks

Secondary Outcomes (2)

• Changes in biomarkers

  24 Weeks

• Tolerability of LAM-002A: completion of open-label study treatment

  12 Weeks

Other Outcomes (5)

• Changes in ALSFRS-R

  28 Weeks

• Changes in Vital Capacity

  24 Weeks

• Permanent assisted ventilation-free survival

  24 Weeks

Study Arms (2)

LAM-002A

EXPERIMENTAL

LAM-002A will be administered orally in five 25 mg capsules twice a day (250 mg total daily dose).

Drug: LAM-002A

Placebo

PLACEBO COMPARATOR

Placebo matching LAM-002A will be administered orally in 5 capsules twice a day.

Other: Placebo

Interventions

LAM-002A DRUG

LAM-002A (apilimod dimesylate) is formulated in capsules containing 25 mg of apilimod dimesylate. The capsule is Swedish orange, size 0.

LAM-002A

Placebo OTHER

Microcrystalline cellulose in Swedish orange, size 0 capsules.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of C9ORF72-associated ALS with BOTH of the following:
• Documentation of a clinical genetic test demonstrating the presence of a pathogenic repeat expansion in C9ORF72. If there is a strong clinical suspicion for C9ALS based on C9-positive family history and El Escorial Criteria consistent with a diagnosis of ALS, clinical testing for the C9ORF72 repeat expansion may be performed with study screening labs at the discretion of the Site Investigator (SI), medical monitor, and study sponsor.
• AND
• Must meet possible, laboratory-supported probable, probable, or definite criteria for diagnosing ALS by revised El Escorial criteria (Brooks 2000).
• Age 18 or older
• Capable of providing informed consent at the Screening Visit and complying with study procedures throughout the study, in the SI's opinion, and at the discretion of the medical monitor and study sponsor.
• In the case that a participant lacks the ability to provide informed consent. Informed consent will be sought from the participant's surrogate representative.
• Able to safely swallow study drug capsule at screening and throughout study. May use thickened substances to assist in swallowing drug.
• Vital Capacity greater than and equal to 50% of predicted at the time of the Screening Visit measured by Slow Vital Capacity (SVC), or, if required due to COVID-19 pandemic-related restrictions and with Sponsor approval, Forced Vital Capacity (FVC) measured in-person or via telemedicine.
• Participants must either not take or be on a stable dose of riluzole (as either a tablet or oral suspension) for greater than 30 days prior to the Screening Visit. Riluzole-naïve participants are permitted in the study.
• Participants must either not take edaravone or have completed at least one 14-day cycle with plan for continuation of edaravone prior to the Screening Visit. Participants must be off cycle and at least 2 days after the last dose administration of edaravone at the time of study visit. Edaravone-naïve participants are permitted in the study.
• Participants must be able to complete all study procedures, including the lumbar punctures (LP) at the time of the Screening Visit, in the SI's opinion.
• Geographically accessible to the site.

You may not qualify if:

• Clinically significant unstable medical condition (other than ALS) that would pose a risk to the participant, according to the SI's judgment \[e.g., cardiovascular instability, systemic infection, or clinically significant laboratory abnormality or electrocardiogram (ECG) changes\].
• Gastrointestinal disease (e.g., gastric, or intestinal bypass surgery, jejunostomy tube, pancreatic enzyme insufficiency, malabsorption syndrome, symptomatic inflammatory bowel disease, chronic diarrheal illness, bowel obstruction) that might interfere with drug absorption or with interpretation of gastrointestinal AEs. Gastrostomy tube placement is allowed prophylactically or to supplement nutrition/hydration but may not be used for study drug administration.
• Hepatic profile showing any of the following:
• i. Serum alanine aminotransferase (ALT) greater than 5 × upper limit of normal (ULN).
• ii. Serum aspartate aminotransferase (AST) greater than 5 × ULN.
• iii. Serum bilirubin greater than 1.5 × ULN.
• c. Renal profile showing an estimated creatinine clearance (eClCR) less than 30 mL/minute (with eClCR to be calculated by the method at the laboratory performing the serum creatinine test).
• Presence of a neurodegenerative cognitive or motor syndrome (e.g., Alzheimer's disease, Parkinson's disease) not related to the C9ORF72 repeat expansion.
• Presence of unstable psychiatric disease or substance abuse that would impair ability of the participant to provide informed consent, in the SI's opinion.
• Active cancer or history of cancer, except for the following: basal cell carcinoma or successfully treated squamous cell carcinoma of the skin, cervical carcinoma in situ, prostatic carcinoma in situ, or other malignancies curatively treated and with no evidence of disease recurrence for at least 3 years. Active cancer includes cancers with current disease manifestations or therapy that could adversely affect subject safety and longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results.
• Prior solid organ transplantation.
• Ongoing immunosuppressive therapy including systemic or enteric corticosteroids at screening or for the duration of the trial, at the discretion of the site investigator and medical monitor.
• Use within 5 days prior to randomization or for the duration of the trial of a strong inhibitor or inducer of cytochrome P450 (CYP) 3A4 or expected requirement for chronic use of a strong inhibitor or inducer of CYP3A4 during study therapy.
• Use within 5 days prior to randomization or for the duration of the trial of drug that is a moderate-to-strong substrate of CYP2C9 (including warfarin, tolbutamide, phenytoin, glimepiride) or expected requirement for chronic use of such drugs during study therapy, at the discretion of the site investigator and medical monitor.
• Use of investigational treatments for ALS (off-label use or active participation in a clinical trial) within 5 half-lives (if known) or 30 days (whichever is longer) prior to the Screening Visit.

Sponsors & Collaborators

• OrphAI Therapeutics: lead

Study Sites (3)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Babu S, Nicholson KA, Rothstein JD, Swenson A, Sampognaro PJ, Pant P, Macklin EA, Spruill S, Paganoni S, Gendron TF, Prudencio M, Petrucelli L, Nix D, Landrette S, Nkrumah E, Fandrick K, Edwards J, Young PR. Apilimod dimesylate in C9orf72 amyotrophic lateral sclerosis: a randomized phase 2a clinical trial. Brain. 2024 Sep 3;147(9):2998-3008. doi: 10.1093/brain/awae109.

  PMID: 38606777 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Frontotemporal Dementia With Motor Neuron Disease

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Suma Babu, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, placebo-controlled

Study Record Dates

• First Submitted: November 17, 2021
• First Posted: December 20, 2021
• Study Start: December 23, 2021
• Primary Completion: January 11, 2023
• Study Completion: May 31, 2025
• Last Updated: June 22, 2025

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)