Welcome to the website of Sirius and Celeste, two clinical trials for retinitis pigmentosa and Usher syndrome. This page provides individuals, their families and supporters with information about the trials and trial participation.

What are Sirius and Celeste?

What are Sirius and Celeste

Sirius and Celeste are the names of two clinical trials that aim to find out whether the investigational RNA therapy ultevursen (previously named QR-421a) is effective and safe for people with retinitis pigmentosa and Usher syndrome due to mutations in exon 13 of the USH2A gene. These Phase 2/3 clinical trials have been planned after positive findings in a Phase 1/2 clinical trial named Stellar.

If you are interested in joining one of these two trials, please read about the eligibility criteria.

Sirius logo
Celeste logo
What is ultevursen?

What is ultevursen (QR-421a)

Ultevursen is an investigational RNA therapy that is designed to skip exon 13 in the RNA with the aim to stop vision loss in people that have retinitis pigmentosa due to a mutation in exon 13 of the USH2A gene.

In the first clinical trial of ultevursen, the Stellar study, 14 participants received treatment with ultevursen once in one eye and 6 additional participants received a sham treatment. Results from the Stellar study showed a benefit in the ultevursen treated eyes in comparison to the untreated eyes across multiple vision tests. This benefit was seen in participants with both advanced vision loss as well as early to moderate vision loss. Ultevursen was also observed to be well tolerated with no serious adverse events reported during the trial.

An ophthalmologist performing an eye exam.
How are the trials set up?

How are the clinical trials set up

Clinical trials are used by researchers to find out whether new medicines are effective and safe. Because retinitis pigmentosa is a progressive disease and symptoms change over time, we have designed two clinical trials to best measure the effects of ultevursen on people’s vision.

The Sirius study is for people with advanced vision loss and the Celeste study for people with early to moderate vision loss.

Key aspects of the Sirius and Celeste trials are listed below.

  • In total, the two studies will enroll around 200 adults (age 18 and up) and children (age 12 and up) that have vision loss due to an USH2A exon 13 mutation;
  • The studies aim to find out whether ultevursen is effective at stopping vision loss and whether it is safe and well-tolerated;
  • All participants can receive ultevursen during the trials, but the dose level and start of dosing differ per group. Study participants are randomly assigned to one of the three groups of equal size, and will be unaware of which group they are assigned to:
  • Group 1: receive intravitreal injections (injection into the eye) with dose regimen 1 of ultevursen.
  • Group 2: receive intravitreal injections with dose regimen 2 of ultevursen.
  • Group 3: receive the sham procedure. This procedure mimics an intravitreal injection, but no injection and no study medicine are given. After the initial sham treatment period, this group can receive ultevursen at one of the two dosing regimens for the remaining part of the trial.

Participants receive the study medicine or the sham procedure up to 5 times in the chosen (study) eye, which is the eye with the worse vision. The treatment or sham procedure is given on day 1, month 3 and then every 6 months thereafter.

Are the studies for me?

Are Sirius and Celeste for me

The information below outlines the main criteria for participation in the trials. Participants must:

  • Have an established genetic diagnosis of retinitis pigmentosa caused by a mutation in exon 13 of the USH2A gene, such as c.2299delG (see this table for all known mutations in exon 13);
  • have a visual acuity of 30 letters or better as measured with an ETDRS chart (20/250 or better on the Snellen chart);
  • be 12 years of age or older;
  • have no other significant ocular conditions that may impact study participation;
  • will not participating in another clinical study during the trial.

How to participate in the clinical trial

We recommend that you discuss your situation and suitability for one of the two clinical trials with your doctor.

If you would like more information or when you are interested in joining the clinical trials, please fill out the form below and we will get back to you.

The studies are currently open at the following locations:

  • Retina Foundation of the Southwest

    Dallas, Texas
    Contact: Martin Klein
    mklein@retinafoundation.org   
    Principal Investigator: David G Birch

What is RP?

What is USH2A mediated retinitis pigmentosa

Retinitis pigmentosa (RP) is an inherited retinal disease that leads to vision loss and blindness. Symptoms usually start with night blindness during childhood and further progress with loss of side (peripheral) vision leading to tunnel vision. Loss of central vision appears during adulthood and blindness is frequent in adulthood.

RP can exist in combination with hearing loss, this disease is called Usher syndrome. Usher syndrome is the leading cause of combined deafness and blindness. 

RP is a genetic disease that causes a mistake, or mutation, in the patient’s RNA. Because of the mutation, an essential protein in the eye is not produced or cannot function, and this leads to the deterioration of the light detecting cells in the retina. Both Usher syndrome and RP can be caused by mutations in the USH2A gene and often these mutations appear in a specific part, called exon 13. Because of the mutation, the USH2A RNA cannot produce a functional Usherin protein that plays a role in the development of both the ear and eye. 

In the Western world, up to 16,000 people have vision loss due to mutations in exon 13 of the USH2A gene. To date, there are no therapies approved that treat the vision loss associated with USH2A exon 13 mutations.

If you would like to find out more about RP and other inherited retinal diseases, visit the website of the Foundation Fighting Blindness.

What are mutations in exon 13 of the USH2A gene

Every gene is made up of multiple parts called exons that together contain the information to build one specific protein. The USH2A gene has 72 exons that together provide the information to produce the Usherin protein. Many RP-causing mutations are known to occur in one particular part, exon 13, of the USH2A gene. Below we have listed mutations in exon 13 that are known to cause RP.

RP-causing mutations in USH2A exon 13

Mutation

DNA format

Protein format

1

c.2209C>T

p.(Arg737*)

2

c.2242C>T

p.(Gln748*)

3

c.2276G>T

p.(Cys759Phe)

4

c.2299delG

p.(Glu767Serfs*21)

5

c.2332G>T

p.(Asp778Tyr)

6

c.2391_2392del

p.(Cys797*)

7

c.2414G>C

p.(Gly805Ala)

8

c.2431A>T

p.(Lys811*)

9

c.2431_2432del

p.(Lys811Aspfs*11)

10

c.2440C>T

p.(Gln814*)

11

c.2445C>A

p.(Cys815*)

12

c.2525dup

p.(Leu843Profs*8)

13

c.2541C>A

p.(Cys847*)

14

c.2551A>T

p.(Lys851*)

15

c.2610C>A

p.(Cys870*)

16

c.2653C>T

p.(His885Tyr)

17

c.2755C>T

p.(Gln919*)

18

c.2761del

p.(Leu921Cysfs*46)

19

c.2776C>T

p.(Arg926Cys)

20

c.2797C>T

p.(Gln933*)

21

c.2802T>G

p.(Cys934Trp)

Source: databases.lovd.nl. As new mutations are being discovered in ongoing research this list may not be complete. For each mutation both the DNA and protein formats are given because genetic test results may provide both or one of the formats. Explanation of codes: ‘c.’ stands for complementary DNA, the number gives the position in the gene, the letters explain what has changed, for example 2209C>T means the C at position 2209 was changed into a T and 2299delG means that the G at position 2299 was deleted from the gene. ‘p’ stands for protein, the letters and numbers explain what amino acid (building block of a protein) was changed, for example Arg737 means the amino acid arginine at position 737 changed. ‘*’ means protein production is stopped at that position and Cys759Phe means the cysteine at position 759 changed into a phenylalanine.

FAQ

Frequently asked questions

Below you will find answers to the most frequent questions about the Sirius and Celeste trials.

  • Intravitreal injection is one of the most commonly performed procedures for eye diseases. The inside of the eye is filled with a jelly-like fluid (vitreous). During an intravitreal injection, the eye doctor will inject medicine into the vitreous with a very small needle, after numbing the eye. The patient may feel some pressure but no pain.

  • An RNA therapy is designed to correct the mistake, or mutation, in the RNA of someone with a genetic disease. By correcting the mistake, the RNA can then be used to create the protein that the cell needs, taking away the underlying cause of the disease.

  • Yes, travel and accommodation costs will be covered.

  • While available information on ultevursen is encouraging, there is still much to learn about ultevursen and its effects. Therefore, ultevursen is currently not available outside clinical trials.

  • People participate in clinical trials for different reasons. Some participate because they want to learn more about their disease. Others participate because they want to help with the development of new treatments that could help them and others in the future.

    During a clinical trial, participants are carefully monitored. In addition to eye tests, general safety tests may be performed during study visits, such as blood tests, blood pressure, heart rate and temperature.

Contact us

Contact us

If you would like more information on our clinical trials, please contact us using the form below.

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