ANQUR trial

QRL-201

QRL-201 is an antisense oligonucleotide (ASO). ASOs are small pieces of synthetic DNA or RNA used to alter the activity of proteins; they could then have an effect on malfunctioning biological processes that cause disease. It has been demonstrated that many ALS patients have a shortened (improperly spliced) STATHMIN-2 (STMN2) protein in certain nerve cells. As a result, this protein cannot perform its function in the body. QRL-201 is being investigated to correct this improper splicing and restore the STMN2 protein to its normal length, allowing it to regain its function.

Study design

The ANQUR Phase 1 clinical trial is a double-blind, placebo-controlled study. Placebo-controlled means that the efficacy of QRL-201 is compared with a placebo. A placebo is a drug without an active ingredient. Participants are randomly assigned to either QRL-201 or the placebo.

The total duration of the study is approximately 64 weeks, consisting of a screening period (4 weeks), a treatment period (12 weeks), and a follow-up period (48 weeks).

In this study, the amount of the study drug (dose) was gradually increased in the first two groups of people. This was done until the highest dose that does not cause harmful side effects was found. After the highest dose is found, approximately 16 participants with C9orf72 and approximately 32 sporadic ALS participants will be enrolled.

During the treatment period, study participants will have a 75% chance of receiving QRL-201 and a 25% chance of receiving placebo. The study drug will be administered intrathecally, also known as through an epidural. Participants will be given the study drug or placebo five times during the study.

There will be 27 visits during the study. These may include telephone consultations or hospital visits. A visit takes about two-to-eight hours. After the first dose, clinical trial participants will have a 24-hour safety check on site. This means study participants must stay in the hospital for at least 24 hours after the first dose.

Please be assured that the highest standards for patient safety and care will be maintained throughout the course of this trial.

Study participation

The main eligibility criteria for participating in the ANQUR clinical trial are:

• You are between 18 and 80 years of age
• The onset of the first symptom leading to the diagnosis of ALS was ≤24
• months at the time of the first visit for this study
• Your lung function is at least 51%
• You are willing to undergo an epidural
• You are not taking blood thinners

Note: This list is not exhaustive, but these are the main eligibility criteria.

During the length of the clinical trial, study participants may continue treatment with riluzole.

Registration and more information

Please read the patient information carefully and discuss the study with your physician, as well as friends and family, as appropriate. If you are interested in the ANQUR clinical trial and meet the inclusion criteria, please contact the UMC Utrecht directly by sending an email to trialals@umcutrecht.nl. Please include your name, date of birth, phone number and the name of this study (ANQUR trial).