Trial Outcomes & Findings for Erythrocytes-Mediated Delivery Of Dexamethasone 21-Phosphate In Steroid-Dependent Ulcerative Colitis (NCT NCT01171807)

Last Updated: 2024-09-24

Results Overview

Patients were considered responder if, at the EoS, one of the following occurred: * Disease remission (Powell Tuck index ≤ 3 or CDAI \< 150) and withdrawal of oral steroids therapy from at least the second treatment procedure; * Disease marked improvement vs basal conditions (at least 5 point decrease in Powell Tuck or 150 point decrease in CDAI score) and withdrawal of oral steroids therapy from at least the second treatment procedure. The Powell-Tuck index was calculated by adding the subscores given by 7 items. A total score \< 10 indicated a mild activity of the UC, and a total score \>14 a severe one. The higher the score the worse the outcome. Crohn Disease Activity Index (CDAI) was a tool that combines subjective parameters, with objectives parameters. The score given to each parameter was inserted in an algorithm which provided the final Index value. A moderate CD showed a CDAI score between 220 and 450, while a CDAI \> 450 was an activity index indicating a severe disease.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)

Results posted on

2024-09-24

Participant Flow

The total size of 40 patients was originally selected. However the final sample size of 33 was considered reasonable for the purpose of the study , due to the explorative nature of the protocol. Patients were assigned to a treatment plan consisting of a treatment procedure every 15 or 30 days for a total of 3 or 6 procedures, respectively.

Thirty-three (33) outpatients were enrolled into the study: nineteen subjects were steroid dependant (8 and 11 affected from Chron's Disease and Ulcerative Colitis, respectively) while 14 were patients with Ulcerative Colitis refractory to mesalazine.

Participant milestones

Participant milestones
Measure	Dex 21-P In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P. Dex 21-P: At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.	Placebo In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P. Placebo: Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P
Overall Study STARTED	21	12
Overall Study Intention to Treat (ITT) Population	21	12
Overall Study Per Protocol (PP) Population	18	11
Overall Study Safety (SAF) Population	21	12
Overall Study COMPLETED	15	8
Overall Study NOT COMPLETED	6	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Dex 21-P In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P. Dex 21-P: At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.	Placebo In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P. Placebo: Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P
Overall Study Treatment failure	2	4
Overall Study Non compliance	1	0
Overall Study Lost to Follow-up	3	0

Baseline Characteristics

Erythrocytes-Mediated Delivery Of Dexamethasone 21-Phosphate In Steroid-Dependent Ulcerative Colitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dex 21-P - ITT n=21 Participants In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P. Dex 21-P: At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.	Placebo - ITT n=12 Participants In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P. Placebo: Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P	Total n=33 Participants Total of all reporting groups
Age, Continuous	43 years STANDARD_DEVIATION 10.1 • n=5 Participants	40 years STANDARD_DEVIATION 13.2 • n=7 Participants	42 years STANDARD_DEVIATION 11.2 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	6 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment Italy	21 participants n=5 Participants	12 participants n=7 Participants	33 participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)

Population: ITT Population: subjects who underwent at least one treatment procedure

Outcome measures

Outcome measures
Measure	Dex 21-P - ITT n=21 Participants In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P. Dex 21-P: At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.	Placebo - ITT n=12 Participants In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P. Placebo: Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P
The Proportion of Patients Responders to Dex 21-P vs Placebo Responders	15 Participants	1 Participants
The Proportion of Patients Responders to Dex 21-P vs Placebo Non Responders	6 Participants	11 Participants

SECONDARY outcome

Timeframe: From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)

Population: Intent To Treat population (ITT): subjects who underwent at least one treatment procedure;

Blood levels of endogenous cortisol were determined before the first and 15 days/one month after the last intra-erythrocytes infusion, according to the assigned treatment scheme planned for each patient. As steroids suppress ACTH production resulting in lowering cortisol levels, the assessment of this parameter was intended to investigate the ability of the dexamethasone intra-erythrocytes administration in minimising this steroid adverse effect. In child, from 1 to 16 years, the total serum cortisol reference range is 5-23 mcg/dL at 8 am, and 3-13 mcg/dL at 4 pm.

Outcome measures

Outcome measures
Measure	Dex 21-P - ITT n=21 Participants In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P. Dex 21-P: At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.	Placebo - ITT n=12 Participants In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P. Placebo: Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P
Change From Baseline in Endogenous Cortisole Blood Level After Receiving the Study Treatment	3.3 mcg/dL Standard Deviation 2.12	2.3 mcg/dL Standard Deviation 5.71

SECONDARY outcome

Timeframe: From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)

Population: Intent To Treat population (ITT): subjects who underwent at least one treatment procedure

The erythrocyte sedimentation rate (ESR) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of inflammation. To perform the test, anticoagulated blood is traditionally placed in an upright tube (Westergren tube) and the distance which the red blood cells fall is measured and reported in millimetres at the end of one hour. ESR was evaluated as supportive data for the assessment of the intestinal disease severity. It was determined before the first and 15 days/one month after the last intra-erythrocytes infusion, according to the assigned treatment scheme planned for each patient. ESR normal values in blood were from 0 to 20 mm/hour. Higher values are considered abnormal both in adults and in children. For ESR values \> 100 mm/hour, there is a high probability that an underlying cause would be found upon investigation.

Outcome measures

Outcome measures
Measure	Dex 21-P - ITT n=21 Participants In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P. Dex 21-P: At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.	Placebo - ITT n=12 Participants In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P. Placebo: Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P
Change From Baseline in Inflammatory Indexes After Receiving the Study Treatment: Erythrocyte Sedimentation Rate (ESR)	-4.9 mm/h Standard Deviation 25.88	-9.3 mm/h Standard Deviation 15.44

SECONDARY outcome

Timeframe: From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)

Population: Intent To Treat population (ITT): subjects who underwent at least one treatment procedure;

CRP is a protein produced by the liver. A C-reactive protein test measures the level of C-reactive protein (CRP) in a blood sample. Normal levels of blood C-reactive protein are low (0.3 to 1.0 mg/L). In case of inflammation liver releases more CRP into your bloodstream: results equal to or greater than 8 mg/L or 10 mg/L are considered high. High levels of CRP may indicate a serious health condition that causes inflammation. C-reactive protein (CRP) was determined before the first and 15 days/one month after the last intra-erythrocytes infusion, according to the assigned treatment scheme planned for each patient. Inflammation parameters (CRP) were evaluated as supportive data for the assessment of the intestinal disease severity. C-reactive protein was measured in milligrams per liter (mg/L). Results equal to or greater than 8 mg/L or 10 mg/L were considered high.

Outcome measures

Outcome measures
Measure	Dex 21-P - ITT n=21 Participants In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P. Dex 21-P: At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.	Placebo - ITT n=12 Participants In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P. Placebo: Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P
Change From Baseline in Inflammatory Indexes After Receiving the Study Treatment: C-reactive Protein (CRP)	-0.5 mg/L Standard Deviation 4.35	-2.2 mg/L Standard Deviation 7.27

SECONDARY outcome

Timeframe: From baseline to End of treatment = 28 weeks ± 5 days (in mesalazine refractory UC patients)

Population: Intent To Treat population (ITT): subjects who underwent at least one treatment procedure. Herein only CD or UC steroid-dependant patients were analysed.

The Baron score was an endoscopic grading system for ulcerative colitis. Four grades are defined (0-3) by the Baron score according to the severity of macroscopic inflammation of the rectal mucosal appearances at rigid sigmoidoscopy: 0 = normal mucosa (ramifying vascular pattern clearly visible, no spontaneous bleeding, no bleeding to light touch); 1. = abnormal mucosa but non-haemorrhagic appearances between scores 0 and 2; 2. = moderately haemorrhagic (bleeding to light touch, but no spontaneous bleeding seen ahead of the instrument on initial inspection); 3= severely haemorrhagic (spontaneous bleeding seen ahead of instrument at initial inspection and bleeds to light touch). The higher the score the worst the outcome. Due to the nature of the score, its assessment was limited to patients suffering from UC, only. (CD or UC steroid-dependant patients were planned to receive the study treatment procedure every 30 days for a total of 6 administrations)

Outcome measures

Outcome measures
Measure	Dex 21-P - ITT n=11 Participants In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P. Dex 21-P: At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.	Placebo - ITT n=8 Participants In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P. Placebo: Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P
Count of Partecipants, Suffering From Mesalazine Refractory UC, With Modification in Endoscopic Result (Baron Score) From 1 to 2 score	3 Participants	0 Participants
Count of Partecipants, Suffering From Mesalazine Refractory UC, With Modification in Endoscopic Result (Baron Score) From 0 to 0 score	1 Participants	0 Participants
Count of Partecipants, Suffering From Mesalazine Refractory UC, With Modification in Endoscopic Result (Baron Score) From 1 to 0 score	0 Participants	1 Participants
Count of Partecipants, Suffering From Mesalazine Refractory UC, With Modification in Endoscopic Result (Baron Score) From 1 to 1 score	0 Participants	2 Participants
Count of Partecipants, Suffering From Mesalazine Refractory UC, With Modification in Endoscopic Result (Baron Score) From 2 to 1 score	0 Participants	3 Participants
Count of Partecipants, Suffering From Mesalazine Refractory UC, With Modification in Endoscopic Result (Baron Score) From 2 to 2 score	2 Participants	1 Participants
Count of Partecipants, Suffering From Mesalazine Refractory UC, With Modification in Endoscopic Result (Baron Score) From 3 to 1 score	2 Participants	0 Participants
Count of Partecipants, Suffering From Mesalazine Refractory UC, With Modification in Endoscopic Result (Baron Score) From 3 to 2 score	1 Participants	1 Participants
Count of Partecipants, Suffering From Mesalazine Refractory UC, With Modification in Endoscopic Result (Baron Score) From 3 to 3 score	2 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)

Population: Safety Population: all patient included in ITT population

At each access to the clinic (except at the baseline visit one), patients were questioned and/or examined for evidence of adverse events. An adverse event was defined as any untoward medical occurrence or unfavourable and unintended sign in a subject administered a pharmaceutical product, biologic (at any dose), or medical device, whether or not considered related to the use of that product. This includes the onset of new illness and the exacerbation of pre-existing conditions.

Outcome measures

Outcome measures
Measure	Dex 21-P - ITT n=21 Participants In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P. Dex 21-P: At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.	Placebo - ITT n=12 Participants In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P. Placebo: Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P
Number of Patients Experiencing at Least One TEAE (Not Steroid-related) Patients experiencing at least one TEAE	11 Participants	8 Participants
Number of Patients Experiencing at Least One TEAE (Not Steroid-related) Patients experiencing at least one serious AE	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)

Steroid related adverse events were investigated to assess the ability of the therapeutic approach under study in reducing the occurrence or entity of steroid adverse effects.

Outcome measures

Outcome measures
Measure	Dex 21-P - ITT n=21 Participants In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P. Dex 21-P: At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.	Placebo - ITT n=12 Participants In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P. Placebo: Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P
Number of Patients Experiencing at Least One TEAE (Steroid-related)	3 Participants	3 Participants

Adverse Events

Dex 21-P - SAF

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo - SAF

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dex 21-P - SAF n=21 participants at risk In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P. Dex 21-P: At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.	Placebo - SAF n=12 participants at risk In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P. Placebo: Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P
Gastrointestinal disorders Acute pancreatitis	0.00% 0/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	8.3% 1/12 • Number of events 1 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)

Other adverse events

Additional Information

Irene Maccabruni, M.Sc.

Quince Therapeutics (former Erydel SpA)

Phone: +39 02 36504470

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dex 21-P - SAF n=21 participants at risk In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P. Dex 21-P: At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.	Placebo - SAF n=12 participants at risk In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively. Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval. Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P. Placebo: Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P
Investigations Increase of alkaline phosphatase	0.00% 0/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	8.3% 1/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Investigations Increase on gamma-glutamyl transferase	4.8% 1/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Investigations Increase of lipase	9.5% 2/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Investigations Increase of amylase	4.8% 1/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Investigations Joint aspiration	0.00% 0/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	8.3% 1/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Metabolism and nutrition disorders Sideropenic anemia	4.8% 1/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Metabolism and nutrition disorders Iron deficiency	4.8% 1/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Metabolism and nutrition disorders Loss of appetite	4.8% 1/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Metabolism and nutrition disorders Weight decrease	4.8% 1/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Gastrointestinal disorders Rectorrhage	0.00% 0/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	16.7% 2/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Gastrointestinal disorders Evacuations increase	0.00% 0/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	16.7% 2/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Gastrointestinal disorders Epigastralgia	9.5% 2/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	8.3% 1/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Gastrointestinal disorders Dyspepsia	0.00% 0/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	8.3% 1/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Gastrointestinal disorders Tenesmus	0.00% 0/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	8.3% 1/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Gastrointestinal disorders Diarrhoea	0.00% 0/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	8.3% 1/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Gastrointestinal disorders Abdominal pain	19.0% 4/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Infections and infestations Rhinitis	4.8% 1/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Nervous system disorders Vertigo	4.8% 1/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Skin and subcutaneous tissue disorders Erythema	9.5% 2/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Injury, poisoning and procedural complications Hypotensive crisis	0.00% 0/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	8.3% 1/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Musculoskeletal and connective tissue disorders Osteoporosis	4.8% 1/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Musculoskeletal and connective tissue disorders Articular pain	9.5% 2/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
Vascular disorders Oedema	4.8% 1/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	8.3% 1/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
General disorders Shiver	4.8% 1/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)
General disorders Asthenia	4.8% 1/21 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)	0.00% 0/12 • TEAEs were assessed throughout the study (except at the baseline visit 1) at each access to the clinic. More specifically adverse events were assessed: - steroid-dependant patients: every 30 days up to month 6 (Final Visit) - mesalazine refractory active UC patients: every 15 days up to 45 days (Final Visit)