A Study Exploring the PK/PD Relationship of QRL-101 in Adults With ALS

A Randomized, Placebo-Controlled, Double-Blind, Single-Dose, Phase 1 Study to Explore the PK/PD Relationship of QRL-101 in People Living With ALS

This Phase 1 randomized, placebo-controlled, double-blind study will evaluate the PK/PD relationship of single doses of QRL-101 in 12 ALS participants. The study will also assess safety and tolerability in participants receiving either QRL-101 or placebo.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: QRL-101; Other: Placebo

Detailed Description

This is a randomized, placebo-controlled, double-blind, single-dose, single-site, Phase 1 study to explore the pharmacokinetics (PK) and pharmacodynamics (PD) of single doses of QRL-101 in participants with ALS. In addition, the safety and tolerability of QRL-101 will be evaluated. Single doses of QRL-101 or placebo will be administered as an oral liquid to approximately 12 participants with ALS. The study will explore the PK, PD, and PK/PD relationship among three dose levels of QRL-101 and placebo. The randomization will be 1:1:1:1 for the four study groups and will be conducted in 3 blocks (cohorts) of 4, where participants will be randomized 3:1 (QRL-101:placebo) for increasing dose levels of QRL-101.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Netherlands
    • Utrecht, Netherlands, Netherlands, 9728 NZ
      • Universitair Medisch Centrum Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA

1. Age 18 to 80 years of age inclusive at the time of signing the informed consent.
2. Diagnosis of ALS, by either Gold Coast Criteria or El Escorial Criteria (possible, probable laboratory supported, probable, or definite)
3. Clinical chemistry laboratory values within acceptable range for the population, as per investigator judgment.
4. Body mass index of 18 to 32 kg/m2 (inclusive).
5. Willing and able to practice effective contraception.

EXCLUSION CRITERIA

1. Currently enrolled in any other clinical trial involving a study drug, off-label drug or device use, or any other type of medical research judged not scientifically or medically compatible with this study.
2. History or presence of medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric, or neurological disease, convulsions, or any clinically significant laboratory abnormality that, in the judgment of the investigator, indicate a medical problem that would preclude study participation.
3. Off-label use of drugs or devices that are being used or investigated as disease-modifying therapies in ALS
4. Participated in another clinical study within 30 days, or 5 half-lives of the previous investigational product, whichever is greater, prior to the planned randomization date.
5. Taking any prescription or nonprescription medicines that are cytochrome P450 3A4 inducers, inhibitors, or substrates within 30 days or 5 half-lives, whichever is greater, prior to the planned randomization date

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QRL-101; Single doses of QRL-101 will be orally administered. The dose levels may change subject to available nonclinical, clinical, safety, and PK data.	Drug: QRL-101; Single doses of QRL-101 will be orally administered. The dose levels may change subject to available nonclinical, clinical, safety, and PK data.
Experimental: Placebo; Single doses of comparator placebo will be orally administered. The dose levels may change subject to available nonclinical, clinical, safety, and PK data.	Other: Placebo; Single doses of compartor placebo will be orally administered. The dose levels may change subject to available nonclinical, clinical, safety, and PK data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
QRL-101 plasma concentration	Baseline through Follow up (Day 10)
PK/PD Relationship: Strength-Duration Time Constant (SDTC)	Baseline through Follow up (Day 10)

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and Tolerability: Adverse Events (AEs)	Baseline through Follow up (Day 10)
Safety and Tolerability: Serious Adverse Events (SAEs)	Baseline through Follow up (Day 10)
Plasma PK profile: Maximum concentration observed (Cmax)	Baseline through Follow up (Day 10)
Plasma PK profile: Time of maximum drug concentration (Tmax)	Baseline through Follow up (Day 10)
Plasma PK profile: Area under the concentration time curve from time 0 to 24 hours (AUC0-24hr)	Baseline through Follow up (Day 10)

Collaborators and Investigators

• Sponsor: QurAlis Corporation

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2024
• Primary Completion (Actual): August 22, 2025
• Study Completion (Actual): August 22, 2025

Study Registration Dates

• First Submitted: November 27, 2024
• First Submitted That Met QC Criteria: November 27, 2024
• First Posted (Actual): December 3, 2024

Study Record Updates

• Last Update Posted (Estimated): September 2, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: QRL-101-04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No