Trial Outcomes & Findings for Study to Evaluate the Efficacy Safety and Tolerability of Ultevursen in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene (Sirius) (NCT NCT05158296)

Last Updated: 2024-07-12

Results Overview

Mean change from baseline in best corrected visual acuity(BCVA) based on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

7 participants

Primary outcome timeframe

18 months of treatment versus sham-procedure

Results posted on

2024-07-12

Participant Flow

Participant milestones

Participant milestones
Measure	Ultevursen 60/60 µg 60 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter Ultevursen: RNA antisense oligonucleotide for intravitreal injection	Ultevursen 180/60 µg 180 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter Ultevursen: RNA antisense oligonucleotide for intravitreal injection	Sham-procedure Sham-procedure (no experimental drug administered) on Day 1, Month 3 and every 6 months thereafter Sham-procedure: Sham-procedure (no experimental drug administered)
Overall Study STARTED	2	3	2
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	2	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Ultevursen 60/60 µg 60 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter Ultevursen: RNA antisense oligonucleotide for intravitreal injection	Ultevursen 180/60 µg 180 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter Ultevursen: RNA antisense oligonucleotide for intravitreal injection	Sham-procedure Sham-procedure (no experimental drug administered) on Day 1, Month 3 and every 6 months thereafter Sham-procedure: Sham-procedure (no experimental drug administered)
Overall Study Sponsor Decision	2	3	2

Baseline Characteristics

Study to Evaluate the Efficacy Safety and Tolerability of Ultevursen in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene (Sirius)

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 18 months of treatment versus sham-procedure

Population: Zero participants were analyzed due to premature study termination, per Sponsor decision for reasons unrelated to safety. No subject enrolled reached the primary endpoint target of 18 months, therefore no data is available for analysis.

Mean change from baseline in best corrected visual acuity(BCVA) based on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 27 months

Proportion of patients who maintain vision defined by BCVA loss less than 15 Letters based on ETDRS

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 27 months

Change from baseline in other analyses of Best Corrected Visual Acuity (BCVA)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 27 months

Change from baseline in ellipsoid zone (EZ) area and width as imaged by spectral domain optical coherence tomography (SD-OCT)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 27 months

Change from baseline in Low Luminance Visual Acuity (LLVA)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 27 months

Change from baseline in Microperimetry

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 27 months

Change from baseline in Full-field Stimulus Threshold (FST)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 27 months

As assessed by the Veteran Affairs Low Vision Visual Functioning Questionnaire (VA LV VFQ-20), Patient Global Impressions of Severity (PGI-S) and Patient Global Impressions of Change (PGI-C)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 27 months

Ocular and non-ocular adverse events (AEs)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 27 months

Maximum concentration (Cmax) of ultevursen in serum

Outcome measures

Outcome data not reported

Adverse Events

Ultevursen 60/60 µg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Ultevursen 180/60 µg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Sham-procedure

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Ultevursen 60/60 µg n=2 participants at risk 60 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter Ultevursen: RNA antisense oligonucleotide for intravitreal injection	Ultevursen 180/60 µg n=3 participants at risk 180 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter Ultevursen: RNA antisense oligonucleotide for intravitreal injection	Sham-procedure n=2 participants at risk Sham-procedure (no experimental drug administered) on Day 1, Month 3 and every 6 months thereafter Sham-procedure: Sham-procedure (no experimental drug administered)
Eye disorders Conjunctival haemorrhage	50.0% 1/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	66.7% 2/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Eye disorders Eye pain	50.0% 1/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	33.3% 1/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Eye disorders Visual impairment	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	33.3% 1/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Eye disorders Vision blurred	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	33.3% 1/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Eye disorders Photopsia	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	33.3% 1/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Infections and infestations Urinary tract infection	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	50.0% 1/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Infections and infestations Tonsillitis	50.0% 1/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Infections and infestations Sinusitis	50.0% 1/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Metabolism and nutrition disorders Iron deficiency	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	50.0% 1/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Injury, poisoning and procedural complications Tooth injury	50.0% 1/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Ear and labyrinth disorders Vertigo labyrinthine	50.0% 1/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Musculoskeletal and connective tissue disorders Arthralgia	50.0% 1/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Gastrointestinal disorders Inguinal hernia	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	33.3% 1/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).
Congenital, familial and genetic disorders Hydrocele	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	33.3% 1/3 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).	0.00% 0/2 • up to 10 months for each participant. Study was terminated prematurely, therefore follow-up maximum range is first patient first visit to last patient last visit. Any event/condition noted once the subject receives their first dose of study drug until the End of study visit (30 days +/- 14 days post last dose of study drug).

Additional Information

Zuhal Butuner - Chief Medical Officer

Sepul Bio

Phone: (905) 599-7887

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institution shall be free to publish, present, or use any Data and results arising out of its performance of the protocol. At least 30 days prior to submission for publication, institution shall submit to Sponsor for review and comment any proposed oral or written publication. Institution will consider any such comments in good faith but is under no obligation to incorporate Sponsor's suggestions. The review period for abstracts or poster presentations shall be 30 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ultevursen 60/60 µg n=2 Participants 60 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter Ultevursen: RNA antisense oligonucleotide for intravitreal injection	Ultevursen 180/60 µg n=3 Participants 180 µg loading dose administered on Day 1, 60 µg maintenance dose administered at Month 3 and every 6 months thereafter Ultevursen: RNA antisense oligonucleotide for intravitreal injection	Sham-procedure n=2 Participants Sham-procedure (no experimental drug administered) on Day 1, Month 3 and every 6 months thereafter Sham-procedure: Sham-procedure (no experimental drug administered)	Total n=7 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Age, Continuous	54.0 years STANDARD_DEVIATION 1.4 • n=5 Participants	47.3 years STANDARD_DEVIATION 20.5 • n=7 Participants	56.0 years STANDARD_DEVIATION 4.2 • n=5 Participants	51.7 years STANDARD_DEVIATION 12.7 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Genotype Homozygous	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Genotype Heterozygous	2 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Phenotype Syndromic	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Phenotype Non-Syndromic	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Baseline Best Corrected Visual Acuity (BCVA) - Treated Eye	53.0 letters STANDARD_DEVIATION 14.1 • n=5 Participants	54.7 letters STANDARD_DEVIATION 11.1 • n=7 Participants	59.0 letters STANDARD_DEVIATION 11.3 • n=5 Participants	55.4 letters STANDARD_DEVIATION 10.1 • n=4 Participants
Baseline Best Corrected Visual Acuity (BCVA) - Contralateral Eye	61.0 letters STANDARD_DEVIATION 5.7 • n=5 Participants	71.0 letters STANDARD_DEVIATION 11.3 • n=7 Participants	68.5 letters STANDARD_DEVIATION 2.1 • n=5 Participants	67.4 letters STANDARD_DEVIATION 8.3 • n=4 Participants