What is this study about?

PRIZM is a Phase 2b clinical trial investigating whether Zagociguat improves fatigue (lack of energy), cognitive impairment (e.g. problems with memory, difficulty concentrating) and other symptoms in people living with the mitochondrial disease syndrome MELAS.

By design PRIZM is a blinded, placebo-controlled, crossover study with two treatment periods separated by a washout period. Half of the eligible participants will receive Zagociguat in period 1 and then placebo in treatment period 2 and the other half will receive placebo in period 1 and then Zagociguat in treatment period 2, therefore all participants will receive the treatment in this trial.

Who can take part? 

You may be eligible to participate if you:

• are between 18 and 75 years old
• have a mitochondrial DNA mutation
• have a history of stroke-like episode(s)
• experience fatigue and cognitive issues.

Final eligibility will be determined by the study doctor after the screening visit.

What drug is being tested?

Zagociguat is an investigational medicine that is taken as a once-a-day oral tablet. Zagociguat has been studied in 5 clinical trials, including a Phase 2a trial in participants with MELAS.

What’s involved in taking part?

Participation in the PRIZM study involves several visits and assessments to hospital and several will be conducted at the participant’s home (remote visit). During the remote visits, a home health nurse will come to your home to perform some of the procedures.

The study comprises: screening and baseline period before starting treatment period 1, followed by a washout period, treatment period 2 and a safety follow-up visit after you finish with all study treatments.

During the clinic and home visits you will undergo a series of tests and procedures, such as blood samples, questionnaires, cognitive assessments and a test of strength and endurance of your lower body (30 seconds sit-to-stand test). During the study visits you will also discuss any side-effects you may be experiencing and any medications and supplements you have been taking.

Will there be any costs associated with my participation in the study?

There are no costs for you if you take part. You will receive the study drug or placebo at no cost, and you will not be charged for any study-related procedures.

Any reasonable journey costs (cost of fuel, bus or railway tickets) and subsistence costs will be reimbursed to you, provided they are supported by valid receipts. If you agree, there will be a specialist company that will provide personalised travel support. The company will book and organise payment for hotel accommodation and ground transportation, as well as reimburse travel related expenses: meals, parking, mileage.

Where is the study taking place?

UCL Queen Square Institute of Neurology and Newcastle University.

Are there any risks?

The study involves a series of clinical tests that are often carried out in clinical practice. This includes blood samples, cognitive and exercise tests. Taking blood samples may cause some discomfort or bruising and can cause some people to faint. All of the study and physical tests are safe and routinely used in the clinics.

Zagociguat stimulates an enzyme known as soluble guanylate cyclase (sGC). It has been given to healthy volunteers and to patients with MELAS syndrome in previous clinical studies. Zagociguat was well-tolerated and induced modest blood pressure reductions consistent with other sGC stimulators.

Everyone taking part in the study will be monitored for any adverse effects, however the study team does not know all the effects that the study drug may possibly have on you and side-effects that have not happened before may occur.

Who will benefit?

You may or may not benefit from taking part in this study. However, in the future other people may benefit from this research.

How do I find out more?

If you think you might be eligible and are interested in taking part in this research, or would like any further information, please contact the study team directly:

Newcastle:

Royal Victoria Infirmary – The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Dr Oksana Pogoryelova (Clinical Trial Lead in Mitochondrial Disease) [email protected]

Telephone: 0191 208 3008