Trial Outcomes & Findings for Non-proliferative Diabetic Retinopathy Treated With Runcaciguat (NCT NCT04722991)

NCT ID: NCT04722991

Last Updated: 2025-04-08

Results Overview

DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

109 participants

Primary outcome timeframe

At 48 weeks of treatment

Results posted on

2025-04-08

Participant Flow

The study was conducted at 39 study centers in Europe and US that randomized 109 participants from 17 MAR 2021 (first patient first visit) to 22 APR 2024 (last patient last visit).

Out of the 224 screened participants, 109 participants were randomized and started treatment. 115 participants did not pass screening. The primary reason for screen failure was that one or more inclusion or exclusion criteria were not met by the participant.

Participant milestones

Participant milestones
Measure	Runcacigat (BAY1101042) Participants received runcaciguat gastrointestinal therapeutic system (GITS) tablets and were treated following an intra-individual dose-titration design with three titration steps.	Placebo Participants received matching placebo GITS tablets.
Overall Study STARTED	56	53
Overall Study COMPLETED	38	44
Overall Study NOT COMPLETED	18	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Runcacigat (BAY1101042) Participants received runcaciguat gastrointestinal therapeutic system (GITS) tablets and were treated following an intra-individual dose-titration design with three titration steps.	Placebo Participants received matching placebo GITS tablets.
Overall Study Adverse Event	12	4
Overall Study Death	2	0
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal cirterion met	2	2
Overall Study Other	1	0
Overall Study Non-compliance	0	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Non-proliferative Diabetic Retinopathy Treated With Runcaciguat

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Runcacigat (BAY1101042) n=56 Participants Participants received runcaciguat gastrointestinal therapeutic system (GITS) tablets and were treated following an intra-individual dose-titration design with three titration steps.	Placebo n=53 Participants Participants received matching placebo GITS tablets.	Total n=109 Participants Total of all reporting groups
Age, Continuous	56.4 Years STANDARD_DEVIATION 12.7 • n=93 Participants	57.9 Years STANDARD_DEVIATION 11.5 • n=4 Participants	57.1 Years STANDARD_DEVIATION 12.1 • n=27 Participants
Sex: Female, Male Female	25 Participants n=93 Participants	22 Participants n=4 Participants	47 Participants n=27 Participants
Sex: Female, Male Male	31 Participants n=93 Participants	31 Participants n=4 Participants	62 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) White	54 Participants n=93 Participants	50 Participants n=4 Participants	104 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: At 48 weeks of treatment

Population: per protocol set: all full analysis set (FAS) participants of the respective study part without validity findings.

DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study.

Outcome measures

Outcome measures
Measure	Runcacigat (BAY1101042) n=51 Participants Participants received runcaciguat gastrointestinal therapeutic system (GITS) tablets and were treated following an intra-individual dose-titration design with three titration steps.	Placebo n=52 Participants Participants received matching placebo GITS tablets.
Percentage of Participants With Improvement in DRSS by ≥ 2 Steps at 48 Weeks of Treatment in the Study Eye	0.0 percentage of participants Interval 0.0 to 4.7	1.9 percentage of participants Interval 0.2 to 8.7

SECONDARY outcome

Timeframe: At 48 weeks

Population: per protocol set: all full analysis set (FAS) participants of the respective study part without validity findings.

VTC are defined as occurrence of any of the following AEs: * Proliferative diabetic retinopathy (PDR) (DRSS ≥61) * Any ocular neo-vascularization (retinal or anterior-segment neovascularization) * Center-involved (central Early Treatment Diabetic Retinopathy Study \[ETDRS\] subfield) DME * Drop of Best corrected visual acuity (BCVA) of 10 letters or more from baseline

Outcome measures

Outcome measures
Measure	Runcacigat (BAY1101042) n=51 Participants Participants received runcaciguat gastrointestinal therapeutic system (GITS) tablets and were treated following an intra-individual dose-titration design with three titration steps.	Placebo n=52 Participants Participants received matching placebo GITS tablets.
Percentage Participants With Vision Threatening Complications (VTC) at 48 Weeks of Treatment in the Study Eye	17.6 percentage of participants	11.5 percentage of participants

SECONDARY outcome

Timeframe: At 24 weeks of treatment

Population: per protocol set: all full analysis set (FAS) participants of the respective study part without validity findings.

DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study.

Outcome measures

Outcome measures
Measure	Runcacigat (BAY1101042) n=51 Participants Participants received runcaciguat gastrointestinal therapeutic system (GITS) tablets and were treated following an intra-individual dose-titration design with three titration steps.	Placebo n=52 Participants Participants received matching placebo GITS tablets.
Percentage of Participants With ≥ 2 Steps Improvement in DRSS at 24 Weeks of Treatment in the Study Eye	0.0 percentage of participants Interval 0.0 to 4.8	0.0 percentage of participants Interval 0.0 to 4.7

SECONDARY outcome

Timeframe: At 48 weeks of treatment

Population: per protocol set: all full analysis set (FAS) participants of the respective study part without validity findings.

DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study.

Outcome measures

Outcome measures
Measure	Runcacigat (BAY1101042) n=51 Participants Participants received runcaciguat gastrointestinal therapeutic system (GITS) tablets and were treated following an intra-individual dose-titration design with three titration steps.	Placebo n=52 Participants Participants received matching placebo GITS tablets.
Percentage of Participants With ≥ 3 Steps Improvement in DRSS at 48 Weeks of Treatment on the for Persons Scale	0.0 percentage of participants Interval 0.0 to 4.7	1.9 percentage of participants Interval 0.2 to 8.7

SECONDARY outcome

Timeframe: From first dosing up to 28 days after last dose of study intervention

Population: Safety analysis set (SAF): All participants of the respective study part who took at least one dose of study intervention.

Outcome measures

Outcome measures
Measure	Runcacigat (BAY1101042) n=56 Participants Participants received runcaciguat gastrointestinal therapeutic system (GITS) tablets and were treated following an intra-individual dose-titration design with three titration steps.	Placebo n=53 Participants Participants received matching placebo GITS tablets.
Number of Participants With Treatment Emergent Adverse Event (TEAE)	53 Participants	44 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At 48 weeks of treatment

Population: per protocol set: all full analysis set (FAS) participants of the respective study part without validity findings.

DRSS (Diabetic Retinopathy Severity Scale) is measured on a 13-point scale and was graded centrally for the study.

Outcome measures

Outcome measures
Measure	Runcacigat (BAY1101042) n=51 Participants Participants received runcaciguat gastrointestinal therapeutic system (GITS) tablets and were treated following an intra-individual dose-titration design with three titration steps.	Placebo n=52 Participants Participants received matching placebo GITS tablets.
Percentage of Participants With < 3 Steps Deterioration in DRSS at 48 Weeks of Treatment on the for Persons Scale	78.4 percentage of participants Interval 65.8 to 88.0	80.8 percentage of participants Interval 68.5 to 89.7

Adverse Events

Runcaciguat (BAY1101042)

Serious events: 9 serious events

Other events: 50 other events

Deaths: 2 deaths

Placebo

Serious events: 3 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head

Bayer

Phone: (+) 1-888-8422937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Runcaciguat (BAY1101042) n=56 participants at risk Participants received runcaciguat gastrointestinal therapeutic system (GITS) tablets and were treated following an intra-individual dose-titration design with three titration steps.	Placebo n=53 participants at risk Participants received matching placebo GITS tablets.
Cardiac disorders Acute myocardial infarction	0.00% 0/56 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	1.9% 1/53 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Cardiac disorders Atrial fibrillation	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Cardiac disorders Cardiac arrest	0.00% 0/56 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	1.9% 1/53 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Eye disorders Visual acuity reduced	1.8% 1/56 • Number of events 2 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/56 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	1.9% 1/53 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
General disorders Chest pain	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Infections and infestations Infected skin ulcer	0.00% 0/56 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	1.9% 1/53 • Number of events 2 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Infections and infestations Localised infection	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Infections and infestations Osteomyelitis	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Infections and infestations Septic shock	1.8% 1/56 • Number of events 2 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Infections and infestations Abdominal sepsis	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Infections and infestations Diabetic foot infection	0.00% 0/56 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	1.9% 1/53 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Metabolism and nutrition disorders Hypoglycaemia	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Metabolism and nutrition disorders Hyponatraemia	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Musculoskeletal and connective tissue disorders Plantar fasciitis	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Nervous system disorders Cerebrovascular accident	0.00% 0/56 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	1.9% 1/53 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Nervous system disorders Presyncope	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Nervous system disorders Transient ischaemic attack	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Nervous system disorders Hypoxic-ischaemic encephalopathy	0.00% 0/56 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	1.9% 1/53 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Psychiatric disorders Depression	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Renal and urinary disorders Renal failure	0.00% 0/56 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	1.9% 1/53 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Vascular disorders Hypertension	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Vascular disorders Dry gangrene	1.8% 1/56 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	0.00% 0/53 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.
Vascular disorders Peripheral artery thrombosis	0.00% 0/56 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.	1.9% 1/53 • Number of events 1 • After the first study intervention up to 28 days after the end of study intervention, with an average up to 53 weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, with an average of/ up to 54 weeks.