A 3-way Cross-over Study on the Effects of QRL-101 on Transcranial Magnetic Stimulation and Nerve Excitability in Healthy Participants

NCT06681441 | Completed Phase 1 DMC

• 1 other identifier: QRL-101-05
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, prospective, single-center, randomized, double-blind, placebo-controlled, three-way cross-over study to evaluate the safety and tolerability of QRL-101 and investigate the pharmacodynamic effects of two dose levels of QRL-101 on transcranial magnetic stimulation (TMS) and nerve excitability threshold tracking (NETT) in healthy participants. After screening and training, participants will be randomized to one of six treatment sequences of William's square balanced for first-order carry-over design consisting of two doses of QRL-101 or placebo, with at least seven days between each treatment.

Conditions

Healthy

Keywords

QRL-101

Outcome Measures

Primary Outcomes (2)

• Single pulse TMS-EMG motor evoked potential (MEP) amplitude (μV) compared to placebo

  To compare two dose levels of QRL-101 versus placebo on cortical excitability

  3 study periods, with a washout period of at least 7 days between each visit. Each study period consists of 2 nights and 1 study day.

• mNETT strength-duration time constant (SDTC) compared to placebo SDTC

  To compare two dose levels of QRL-101 versus placebo on peripheral motor nerve excitability

  3 study periods, with a washout period of at least 7 days between each visit. Each study period consists of 2 nights and 1 study day.

Secondary Outcomes (4)

• Other Single pulse TMS-EMG MEP parameters

  3 study periods, with a washout period of at least 7 days between each visit. Each study period consists of 2 nights and 1 study day.

• pEEG: power in the alpha frequency bands in resting state with eyes open and closed

  3 study periods, with a washout period of at least 7 days between each visit. Each study period consists of 2 nights and 1 study day.

• Incidence of AEs and SAEs

  3 study periods, with a washout period of at least 7 days between each visit. Each study period consists of 2 nights and 1 study day.

• Plasma QRL-101 concentrations

  3 study periods, with a washout period of at least 7 days between each visit. Each study period consists of 2 nights and 1 study day.

Study Arms (6)

Treatment Group 1

EXPERIMENTAL

Participants will be randomized into 1 of 6 treatment sequences in a 3-way cross-over

Drug: QRL-101 Dose A; Drug: QRL-101 Dose B; Drug: Placebo

Treatment Group 2

EXPERIMENTAL

Participants will be randomized into 1 of 6 treatment sequences in a 3-way cross-over

Drug: QRL-101 Dose A; Drug: QRL-101 Dose B; Drug: Placebo

Treatment Group 3

EXPERIMENTAL

Participants will be randomized into 1 of 6 treatment sequences in a 3-way cross-over

Drug: QRL-101 Dose A; Drug: QRL-101 Dose B; Drug: Placebo

Treatment Group 4

EXPERIMENTAL

Participants will be randomized into 1 of 6 treatment sequences in a 3-way cross-over

Drug: QRL-101 Dose A; Drug: QRL-101 Dose B; Drug: Placebo

Treatment Group 5

EXPERIMENTAL

Participants will be randomized into 1 of 6 treatment sequences in a 3-way cross-over

Drug: QRL-101 Dose A; Drug: QRL-101 Dose B; Drug: Placebo

Treatment Group 6

EXPERIMENTAL

Participants will be randomized into 1 of 6 treatment sequences in a 3-way cross-over

Drug: QRL-101 Dose A; Drug: QRL-101 Dose B; Drug: Placebo

Interventions

QRL-101 Dose A DRUG

All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.

Treatment Group 1; Treatment Group 2; Treatment Group 3; Treatment Group 4; Treatment Group 5; Treatment Group 6

QRL-101 Dose B DRUG

All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.

Treatment Group 1; Treatment Group 2; Treatment Group 3; Treatment Group 4; Treatment Group 5; Treatment Group 6

Placebo DRUG

All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.

Treatment Group 1; Treatment Group 2; Treatment Group 3; Treatment Group 4; Treatment Group 5; Treatment Group 6

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and postmenopausal women between the ages ≥ 18 and ≤ 55.
• BMI ≥ 18.0 and ≤ 32.0 kg/m2, and body weight ≥ 50 kg, at screening.
• Willing and able to practice effective contraception from the screening through at least 2 days after their last dose of study treatment.
• Participants must be able to communicate effectively (in Dutch) with the study personnel and be willing to comply with the requirements of the study.

You may not qualify if:

• Evidence of any acute or chronic disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study.
• History or presence of conditions which, in the judgment of the investigator, are known to interfere with drug absorption, distribution, metabolism, or excretion.
• History or presence of conditions which might increase the risk of performing TMS (e.g., epilepsy, febrile seizures, intracranial mass lesion, hydrocephalus, clinically significant head injury or trauma, metal objects in the brain or skull, cochlear implant or a deep brain stimulation device)
• Any condition that could interfere with the quality of, or ability to perform, TMS (e.g., an abnormal sleeping pattern, unremovable dreadlocks or hairpieces, or a resting motor threshold (rMT) of more than 75%.

Sponsors & Collaborators

• QurAlis Corporation: lead
• Centre for Human Drug Research, Netherlands: collaborator

Study Sites (1)

Centre for Human Drug Research

Leiden, 2333, Netherlands

Location

Study Officials

• Philip Kremer, PharmD, MD, PhD

  Centre for Human Drug Research

  PRINCIPAL INVESTIGATOR

• K. (Kaye) de Cuba,, MD

  Centre for Human Drug Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: A participant and investigator-blinded, randomized, placebo-controlled design will be used to minimize bias in this study.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized, double-blind, placebo-controlled, 3-way cross-over, single-dose study to investigate the effects of QRL-101 on TMS-EMG-EEG, mNETT, and pEEG in healthy participants.

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: November 8, 2024
• Study Start: October 7, 2024
• Primary Completion: December 24, 2024
• Study Completion: December 24, 2024
• Last Updated: March 25, 2025

Record last verified: 2025-03

Locations

NL (1)