A clinical trial to compare the effectiveness and safety of crovalimab with eculizumab in people with paroxysmal nocturnal hemoglobinuria (PNH)

How does the COMMODORE 1 clinical trial work?

This clinical trial is recruiting people who have paroxysmal nocturnal hemoglobinuria (PNH), a blood disorder that involves the breakdown of red blood cells. In order to take part, patients must have been treated with eculizumab for at least 12–24 weeks, or ravulizumab for at least 16 weeks. Patients with a variation in a specific gene (known as C5 polymorphism) can also take part in this trial.

The purpose of this clinical trial is to compare the effects, good or bad, of crovalimab against eculizumab in patients with PNH. If you take part in this clinical trial, you will receive either crovalimab or eculizumab.

How do I take part in this clinical trial?

To be able to take part in this clinical trial, you must have been diagnosed with PNH, and have been treated with eculizumab or ravulizumab before starting the clinical trial.

You will not be able to take part if you are pregnant or breastfeeding, or have had a disease or disorder affecting your blood system (such as blood clots in the lung/liver/kidney, blocked blood vessels, heart attack) within 6 months before starting the clinical trial. 

If you think this clinical trial may be suitable for you and would like to take part, please talk to your doctor. If your doctor thinks that you might be able to take part in this clinical trial, he/she may refer you to the closest clinical trial doctor. They will give you all the information you need to make your decision about taking part in the clinical trial. You can also find the clinical trial locations on this page.

Your doctor will conduct some tests to make sure you will be able to take the treatments given in this clinical trial. Some of these tests or procedures may be part of your regular medical care. They may be done even if you do not take part in the clinical trial. If you have had some of the tests recently, they may not need to be done again.

Before starting the clinical trial, you will be told about any risks and benefits of participating in the trial. You will also be told what other treatments are available so that you may decide if you still want to participate. 

While taking part in the clinical trial, you will need to either not have heterosexual intercourse or use contraception for safety reasons. 

What treatment will I be given if I join this clinical trial?

This clinical trial is ‘open-label’, which means that everyone involved will know what treatment they are receiving.

If you join this clinical trial, you will be entered into one of three groups:

• Group A: you will receive crovalimab, given as an infusion (into the vein) once on Day 1 of the trial, then as an injection under the skin (subcutaneous) once every week for four weeks. After four weeks, crovalimab will be given as a subcutaneous injection once every four weeks for a total of 24 weeks
• OR Group B: you will receive eculizumab, given as an infusion (into the vein) on Day 1 of the trial, then once every two weeks for a total of 24 weeks 

If you are in Groups A or B, you must be at least 18 years of age and have been treated with eculizumab for at least 24 weeks before the clinical trial. You will have an equal chance of being placed in Group A or B.

If you have not been previously treated with eculizumab for at least 24 weeks, you may still join this clinical trial in another group (not random). This third group (Group C) will include:

• Patients treated with ravulizumab for at least 16 weeks before starting the trial, regardless of age
• Patients aged less than 18 years old and weighing at least 40kg treated with eculizumab for at least 12 weeks before starting the trial 
• Patients treated with eculizumab at a higher-than-approved dose for PNH for at least 12 weeks, regardless of age 
• Patients with a variation in a specific gene (known as C5 polymorphism), and whose condition cannot be controlled well by eculizumab or ravulizumab, regardless of age.

If you are in Group C, you will be given crovalimab as an infusion (into the vein) once on Day 1 of the trial, then as a subcutaneous injection once every week for four weeks. After four weeks, crovalimab will be given as a subcutaneous injection once every four weeks for a total of 24 weeks.

After the 24-week primary treatment period, you will have the opportunity to continue crovalimab treatment (Groups A and C) or switch to crovalimab (Group B) for the extension period, if the clinical trial doctor thinks it is in your best interest. Crovalimab may be given in the extension period for a maximum of 5 years, and then until it becomes available in your country and is accessible to you.

How often will I be seen in follow-up appointments and for how long?

You will be given the clinical trial treatment crovalimab OR eculizumab for up to 24 weeks in the primary treatment period. During the study, you will need to attend regular visits for treatments and other assessments to see how you are responding to the treatment and any side effects that you may be having, until you complete the study. If you are in Groups A and C, you may continue to receive crovalimab after the 24-week study period has ended if it is in your best interests. If you are in Group B, you will have the option to switch to crovalimab or leave the study after you have completed 10 weeks of safety follow-up. You are free to stop this treatment at any time.  

What happens if I am unable to take part in clinical trial?
If this clinical trial is not suitable for you, you will not be able to take part. Your doctor may suggest other clinical trials that you may be able to take part in or other treatments that you can be given. You will not lose access to any of your regular care.

For more information about this clinical trial see the For Expert tab on the specific ForPatient page or follow this link to ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04432584?term=crovalimab&draw=2&rank=1

Trial-identifier: NCT04432584