Clinical Trials Register

Summary
EudraCT Number:	2018-004871-11
Sponsor's Protocol Code Number:	ULA02
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-07-03
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2018-004871-11

A.3

Full title of the trial

RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED DOSE ESCALATION STUDY OF ULARITIDE FOLLOWED BY A 42-HOUR INFUSION FOR THE TREATMENT OF ACUTE KIDNEY INJURY (AKI) IN PATIENTS POST CARDIAC SURGERY

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study, with chance selection of treatment unknown to the patients and doctors, to test the
Ularitide as treatment for Acute Kidney Ingury in patients post cardiac surgery

A.3.2

Name or abbreviated title of the trial where available

TRUST

A.4.1

Sponsor's protocol code number

ULA02

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Cardiorentis AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Cardiorentis AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Cardiorentis AG
B.5.2	Functional name of contact point	CEO
B.5.3	Address:
B.5.3.1	Street Address	Churerstrasse 77
B.5.3.2	Town/ city	Pfäffikon
B.5.3.3	Post code	8808
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41 41 748 60 30
B.5.6	E-mail	info@cardiorentis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ularitide
D.3.4	Pharmaceutical form	Lyophilisate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ULARITIDE
D.3.9.1	CAS number	118812-69-4
D.3.9.2	Current sponsor code	ULARITIDE
D.3.9.3	Other descriptive name	Urodilatin+
D.3.9.4	EV Substance Code	SUB11377MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Lyophilisate for solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute kidney injury in patients post cardiac surgery

E.1.1.1

Medical condition in easily understood language

Kidney failure

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10069339
E.1.2	Term	Acute kidney injury
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part A:
• To investigate the safety, tolerability and dose-effect-relationship of 3 different doses of ularitide on renal and central hemodynamics and on renal excretory function in patients post cardiac surgery, who have developed AKI (as defined in this protocol), and to identify the individual maximum tolerated dose of ularitide in these patients.
Part B:
• To investigate the safety, tolerability, and effect of the individual maximum tolerated ularitide dose identified in Part A for up to an additional 42 hours.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and post-menopausal female patients of ≥ 18 years. Post-menopause is defined as ≥ 12 months after the last menstruation without an alternative medical cause
2. Body mass index ≤ 35 kg/m2
3. Decrease of post-surgery GFR-1h-Crea measured twice approximately 1 hour apart within the first 3 hours post-surgery ≥50% compared to pre-surgery eGFR (CKD-EPI)
4. Index hospitalization for planned cardiac surgery via open sternotomy on cardiopulmonary bypass namely coronary artery bypass graft, valve surgery, thoracic aortic surgery, repair of ventricular septal defect or a combination thereof
5. Preoperative predictive score for cardiac surgery-associated AKI of 3 or higher according to Jiang et al., 201615
6. Hemodynamic stability defined as:
a. Systolic blood pressure (SBP) >90 mmHg in at least two consecutive non-invasive measurements that are at least 60 minutes apart in a 2-hour time window immediately post-surgery
b. No increase in vasopressor and/or inotropic support at the end of a 2-hour time window immediately post-surgery compared to its start
7. Signed written informed consent

E.4

Principal exclusion criteria

1. Documented medical history of renal artery stenosis (≥70%), nephrotic syndrome, renal sclerosis
2. Clinical diagnosis of
a. Severe cardiogenic shock (INTERMACS level I) or extracorporal membrane oxygenation, or any other short-term pre-surgery mechanical circulatory support other than intra-aortal balloon pump
b. Right ventricular infarction
3. Body temperature >38.0°C on the day before surgery
4. Patients started on dialysis prior to surgery or immediately thereafter
5. Pre-surgery eGFR (CKD-EPI) <60 mL/min/1.73 m2 based on serum concentrations of creatinine and cystatin C
6. Treatment with sacubitril-valsartan from the day before surgery until 60 hours post infusion start
7. Advanced cancer or any other acute or chronic consuming disease which could relevantly interfere with the surgery outcome (survival) or success of test treatments
8. Known hypersensitivity to the active substance or to any of the excipients of each investigational medicinal product (verum and placebo) or other natriuretic peptides
9. Known Hepatitis B or C or HIV infection
10. Participation in an interventional clinical drug trial within 1 month prior to randomization
11. Legal incapacity or limited legal capacity
12. Breastfeeding or pregnancy
13. Employees of the sponsor or patients who are employees or relatives of the investigator
14. Patient has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

E.5 End points

E.5.1

Primary end point(s)

Change (absolute and percentage) of glomerular filtration rate based on 1-hour creatinine clearance (GFR-1h-Crea) at the end of the dose escalation phase (6 hours post infusion start) versus (vs) Baseline (mean value from 2 post-surgery screening measurements)

E.5.1.1

Timepoint(s) of evaluation of this end point

6 hours post infusion start

E.5.2

Secondary end point(s)

Efficacy endpoints
• Change (absolute and percentage) of GFR-1h-Crea at the end of the 1st and 2nd dose escalation step, 24 hours post treatment start, the end of treatment and 12 hours post treatment end, respectively, vs Baseline (mean value from 2 post-surgery screening measurements)
• Change (absolute and percentage) in serum and urine creatinine at the end of the 1st, 2nd and 3rd dose escalation step, 24 hours post treatment start, the end of treatment and 12 hours post treatment end, respectively, vs Baseline (mean value from 2 post-surgery screening measurements)
• Change (absolute and percentage) of hourly urine volume at the end of the 1st, 2nd and 3rd dose escalation step, 24 hours post treatment start, the end of treatment and 12 hours post treatment end, respectively, vs Baseline (mean value from 2 post-surgery screening measurements)
• Change (absolute and percentage) of natriuresis at 24 hours post treatment start, the end of treatment and 12 hours post treatment end, respectively, vs Baseline
• Change (absolute and percentage) of resistance index at the end of treatment vs Baseline
• Length of intensive care unit (ICU) stay in hours
• Number of patients requiring renal replacement therapy (RRT) by any modality during the treatment period and up to 12 hours thereafter

E.5.2.1

Timepoint(s) of evaluation of this end point

multiple timepoints

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception