Trial Outcomes & Findings for Influence of Diabetes Control on Treatment of Diabetic Macular Edema With Ranibizumab (NCT NCT02665689)

Last Updated: 2019-11-20

Results Overview

Measured by the difference in ETDRS letters score between month 12 and baseline according to internal guideline of Charité department of ophthalmology.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

4 participants

Primary outcome timeframe

Baseline to 12 months

Results posted on

2019-11-20

Participant Flow

The recruitment has been stopped prematurely in August 2018 by the sponsor after the enrolment of four patients because the enrollment pace was far below target.

Screening period of seven days prior to randomization.

Participant milestones

Participant milestones
Measure	Regular Glycemic Control Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.	Intensified Glycemic Control Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level \< 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.
Overall Study STARTED	2	2
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Regular Glycemic Control Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.	Intensified Glycemic Control Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level \< 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.
Overall Study Adverse Event	1	0
Overall Study Trial termination	1	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Regular Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.	Intensified Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level \< 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.	Total n=4 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=2 Participants	0 Participants n=2 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=2 Participants	0 Participants n=2 Participants	1 Participants n=4 Participants
Age, Categorical >=65 years	1 Participants n=2 Participants	2 Participants n=2 Participants	3 Participants n=4 Participants
Sex: Female, Male Female	0 Participants n=2 Participants	2 Participants n=2 Participants	2 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=2 Participants	0 Participants n=2 Participants	2 Participants n=4 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Number of participants with history of ophthalmic disease	2 Participants n=2 Participants	2 Participants n=2 Participants	4 Participants n=4 Participants
Number of patients with medical history	2 Participants n=2 Participants	2 Participants n=2 Participants	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to 12 months

Population: Of the four enrolled patients, only the two patients had 12-month visit. Since the time point for the evaluation of the primary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus analysis of the primary endpoint was waived.

Measured by the difference in ETDRS letters score between month 12 and baseline according to internal guideline of Charité department of ophthalmology.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 months

Population: At month 6, the two patients in study arm A had received six treatments each; the two patients in study arm B had received three and five treatments, respectively. At month 12, the two patients in study arm B had received three and six treatments, respectively. For none of the patients in study arm A, 12-month data was available.

For the number of treatments at 6, 12, 18 and 24 months, an ANOVA without any covariates was planned to be applied at each endpoint 6, 12, 18 and 24 months. As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus statistical analysis of the endpoint was waived completely. None of the patients reached time points beyond month 12. Results are only shown descriptively. Ranibizumab injections were summed up per study arm as well as cumulative at each time point.

Outcome measures

Outcome measures
Measure	Regular Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.	Intensified Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level \< 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.
Number of Treatments With Ranibizumab up to 6, 12, 18 and 24 Months of Treatment Month 6	12 Ranibizumab injections	8 Ranibizumab injections
Number of Treatments With Ranibizumab up to 6, 12, 18 and 24 Months of Treatment Month 12	—	9 Ranibizumab injections

SECONDARY outcome

Timeframe: Baseline to 12 months

Population: BCVA score compared to baseline.

As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus analysis of the endpoint was waived completely. Time point 24 months was reached by none of the patients due to trial discontinuation. Results are only shown descriptively. Best-corrected visual acuity (BCVA) score is shown as change in ETDRS letters score at the distinct time point compared to baseline. Higher scores mean a better outcome.

Outcome measures

Outcome measures
Measure	Regular Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.	Intensified Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level \< 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.
Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 6, 12, 24 and Baseline Visit Participant 3, month 6	—	3 Letters improved
Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 6, 12, 24 and Baseline Visit Participant 3, month 12	—	3 Letters improved
Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 6, 12, 24 and Baseline Visit Participant 1, month 6	7 Letters improved	—
Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 6, 12, 24 and Baseline Visit Participant 2, month 6	5 Letters improved	—
Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 6, 12, 24 and Baseline Visit Participant 4, month 6	—	8 Letters improved
Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 6, 12, 24 and Baseline Visit Participant 4, month 12	—	10 Letters improved

SECONDARY outcome

Timeframe: Baseline to 12 months

Population: For none of the patients in study arm A 12-month data was available. Time points beyond 6 months (18, 24 months) were reached by none of the patients due to trial discontinuation. Results are only shown descriptively.

As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus analysis of the endpoint was waived completely. None of the patients reached time points beyond month 12 due to trial discontinuation. Results are only shown descriptively. Macular thickness (study eye) is shown as change in thickness \[µm\] compared to individual baseline value. A reduction in thickness means improvement.

Outcome measures

Outcome measures
Measure	Regular Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.	Intensified Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level \< 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.
Macular Thickness Change at 6, 12, 18 and 24 Months Compared to Baseline Participant 1, month 6	-91 µm	—
Macular Thickness Change at 6, 12, 18 and 24 Months Compared to Baseline Participant 2, month 6	-319 µm	—
Macular Thickness Change at 6, 12, 18 and 24 Months Compared to Baseline Participant 3, month 6	—	10 µm
Macular Thickness Change at 6, 12, 18 and 24 Months Compared to Baseline Participant 4, month 6	—	-103 µm
Macular Thickness Change at 6, 12, 18 and 24 Months Compared to Baseline Participant 3, month 12	—	23 µm
Macular Thickness Change at 6, 12, 18 and 24 Months Compared to Baseline Participant 4, month 12	—	-101 µm

SECONDARY outcome

Timeframe: 24 months

Population: Originally, target HbA1c should have been defined individually for each patient by the investigator acc. to the patient's general status by risk factors for vasculopathy (Body-Mass-Index, smoking, blood pressure, lipid Status). However, definition of target HbA1c values was waived and only HbA1c values were documented (not shown here).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 months

Need for PRP is up to the investigator's decision. Assessment was done on every visit. Intended time frame was baseline to 24 months. None of the patients reached time points beyond month 12 due to study discontinuation. Unit of measure is any separate investigator's decision to perform panretinal laser photocoagulation (PRP) for neovascular complications. Each PRP is counted separately.

Outcome measures

Outcome measures
Measure	Regular Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.	Intensified Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level \< 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.
Number of Panretinal Laser Photocoagulation (PRP) Treatments Necessary for Neovascular Complications	1 number of PRPs across participants	1 number of PRPs across participants

SECONDARY outcome

Timeframe: Baseline to 12 months

Population: Patients in study arm A discontinued before month 12. None of the patients reached time points beyond month 12 due to trial discontinuation.

All ocular adverse events presented from baseline to 24 months will be documented.

Outcome measures

Outcome measures
Measure	Regular Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.	Intensified Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level \< 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.
Number of Participants With Retinal Detachment, Central Retinal Artery Occlusion, or Endophthalmitis and/or Ocular Adverse Events That Are Related to Treatment Month 6	0 participants	0 participants
Number of Participants With Retinal Detachment, Central Retinal Artery Occlusion, or Endophthalmitis and/or Ocular Adverse Events That Are Related to Treatment Month 12	—	0 participants

SECONDARY outcome

Timeframe: Baseline to 12 months

All adverse events were documented. Causal relationship to study treatment was assessed by the investigators. Intended time frame was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.

Outcome measures

Outcome measures
Measure	Regular Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.	Intensified Glycemic Control n=2 Participants Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level \< 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment	0 participants	0 participants

Adverse Events

Regular Glycemic Control

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Intensified Glycemic Control

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Regular Glycemic Control n=2 participants at risk Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.	Intensified Glycemic Control n=2 participants at risk Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level \< 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/2 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.	50.0% 1/2 • Number of events 1 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.
Vascular disorders Hypertensive crisis	0.00% 0/2 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.	50.0% 1/2 • Number of events 1 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/2 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.	50.0% 1/2 • Number of events 1 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.
Investigations Blood pressure increased	0.00% 0/2 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.	50.0% 1/2 • Number of events 1 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.
Nervous system disorders Headache	0.00% 0/2 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.	50.0% 1/2 • Number of events 1 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.
Infections and infestations Otosalpingitis	0.00% 0/2 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.	50.0% 1/2 • Number of events 1 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.
Cardiac disorders Coronary artery disease	50.0% 1/2 • Number of events 1 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.	0.00% 0/2 • First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.

Other adverse events

Additional Information

Prof. Dr. Antonia Joussen

Charité University, Berlin

Phone: +49 30 84452331

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place