Clinical Trials Register

Summary
EudraCT Number:	2011-006253-29
Sponsor's Protocol Code Number:	CLI00070
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-02-08
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

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2011-006253-29

A.3

Full title of the trial

A Randomized Controlled Double-Blind Phase 3 Study to Assess Characteristics of S-303 Treated RBC Components and Evaluate Safety and Efficacy in Patients Requiring Transfusion Support of Acute Anemia

A.3.1

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

Not applicable

A.3.2

Name or abbreviated title of the trial where available

Not applicable

A.4.1

Sponsor's protocol code number

CLI00070

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	Cerus Corporation
B.1.3.4	Country	United States
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	Cerus Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Cerus Corporation
B.5.2	Functional name of contact point	Megan Le Ward, Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	2550 Stanwell Drive
B.5.3.2	Town/ city	Concord, California
B.5.3.3	Post code	94520
B.5.3.4	Country	United States
B.5.4	Telephone number	1925288 6013
B.5.5	Fax number	1925288 0190
B.5.6	E-mail	mward@cerus.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	S-303 Treated Red Blood Cells in SAG-M
D.3.2	Product code	Not applicable
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous drip use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Amustaline dihydrochloride
D.3.9.1	CAS number	210584-54-6
D.3.9.2	Current sponsor code	AMRI-21810300
D.3.9.3	Other descriptive name	S 303•2HCl
D.3.10	Strength
D.3.10.1	Concentration unit	mol/l mole(s)/litre
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	10E-9
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	S-303 Treated Red Blood Cells in SAG-M
D.3.9.2	Current sponsor code	Not applicable
D.3.9.3	Other descriptive name	S-303 Treated Red Blood Cells in SAG-M
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
D.3.11.13.1	Other medicinal product type	Blood component for transfusion
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Packed red blood cells in SAG-M additive (preservative) solution [Erythrozytenkonzentrat DRK-Blutspendedienst]
D.2.1.1.2	Name of the Marketing Authorisation holder	DRK- Blutspendedienst Baden-Württemberg-Hessen
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Packed red blood cells in SAG-M additive solution [Erythrozytenkonzentrat DRK-Blutspendedienst]
D.3.2	Product code	10552a/97-1
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous drip use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Red blood cell concentrates
D.3.9.2	Current sponsor code	Not applicable
D.3.9.3	Other descriptive name	Red blood cell concentrates
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
D.3.11.13.1	Other medicinal product type	Blood component for transfusion

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute anemia secondary to cardiovascular surgery.

E.1.1.1

Medical condition in easily understood language

Patients undergoing cardiovascular surgery requiring transfusion of red blood cells.

E.1.1.2

Therapeutic area

Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10054312
E.1.2	Term	Anemia postoperative
E.1.2	System Organ Class	10022117 - Injury, poisoning and procedural complications

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The study is designed to support CE Mark registration for the S-303 Treatment System for Red Blood Cells. The two major objectives are:
(1) In vitro analysis of RBCs: the primary outcome measure is the mean hemoglobin (Hb) content per manufactured RBC unit in each treatment group assessed by a statistical hypothesis of equivalence. The Hb mass available for transfusion in each RBC unit is correlated with the magnitude of the potential post transfusion Hb increment and therefore represents one measure of efficacy. (2) A clinical transfusion study in at least 50 cardiovascular surgery patients to obtain an initial assessment of the therapeutic efficacy of Test RBC units in comparison to Control RBC units. Three exploratory clinical outcome measures will be compared between the Test and Control treatment groups:
a) Incidence of renal insufficiency
b) Incidence of hepatic insufficiency
c) Overall cardiopulmonary function

E.2.2

Secondary objectives of the trial

This clinical transfusion study also includes a full safety assessment.

The results of this study will facilitate the design of a future more substantial clinical trial in the same patient population to support specific blood product registrations using the device.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The study will enroll sufficient patients to obtain at least 50 patients with acute anemia who receive at least one RBC component of the assigned treatment type by transfusion during or following an elective cardiac surgery procedure.
In order to minimize the number of patients who enter the study but are not evaluable because they do not receive an RBC transfusion, only patients with a relatively high probability for RBC transfusion will be enrolled. The Transfusion Risk Understanding Screening Tool (TRUST) Score has been validated to predict the likelihood of RBC transfusion in this population. For this study, only patients with a high probability to receive a transfusion as determined by the Investigator OR patients with a TRUST Score of 3 or greater will be eligible for enrollment. The TRUST Score (Alghamdi 2006) is an integer from zero to eight (inclusive); one point is assigned for each of the following elements:
• Hb < 13.5 gm/dL
• Weight < 77 Kg
• Female
• Age > 65 years
• Non-elective surgery
• Serum Cr > 1.36 mg/dL
• Previous cardiac surgery
• Non-isolated surgical procedure
INCLUSION CRITERIA:
1. Must be age 18 years or older
2. Must be willing to use an acceptable form (as approved by the Investigator or designee) of contraception while on study
3. Must be readily available by telephone
4. Must be willing to participate in the second 6MWT at 7 to 10 days after discharge
5. Must provide an informed consent for study participation and have signed an EC-approved informed consent
6. Must have a negative crossmatch to S-303 treated RBCs at study entry
7. Must have a blood type of either A+ or O+
8. Patients must have a likelihood of receiving a transfusion as determined by the Investigator OR a TRUST Score of ≥3 at study entry
9. Must be scheduled to receive one of the following operative procedures:
•Coronary artery bypass graft only, first procedure.
•Valve repair or replacement only, first procedure.
•A combination of first time CABG and valve repair or replacement.

After consultation with the Medical Monitor, provision can be made to enroll patients who may meet these general criteria but whose surgical procedure is not precisely described in the above categories. Such patients will be classified as “other” with their explicit condition reported with other study data.

E.4

Principal exclusion criteria

Any of the following criteria will exclude a potential patient from participation in the study:
1. A positive pregnancy test result
2. Inability of patient to comply with the protocol in the opinion of the Investigator or attending physician
3. Breast-feeding of an infant or child
4. Active autoimmune hemolytic anemia, or a positive Direct Antiglobulin Test (DAT) result
5. Treatment with any medication that is known to adversely affect red blood cell viability
6. Emergent or salvage surgical status at the time of surgery defined as follows:
•Presence of ongoing ischemia including angina at rest despite maximal medical therapy.
•Acute evolving myocardial infarction within 24 hours before surgery.
•Pulmonary edema requiring intubation.
•Presence of shock or hemodynamic instability with or without circulatory support.
•Systolic blood pressure < 80 mm Hg and/or Cardiac Index < 1.8 despite medical intervention (intravenous inotropes or similar pharmacologic agents).
•Cardiopulmonary resuscitation in the 24 hours prior to surgery or anesthesia induction.
•Requiring an intra-aortic balloon pump or ventricular assist device.
7. Participation in any one of the following types of clinical studies either concurrently or within the previous 28 days: investigational blood products, pharmacologic agents or imaging materials, including dyes, investigational surgical techniques, or devices. Studies of nutrition, psychology, or socioeconomic issues are not grounds for exclusion
8. Current diagnosis of either chronic or acute renal failure (requiring dialysis) OR a serum creatinine greater than or equal to 1.8 mg/dL within 30 days prior to the start of surgery
9. Current diagnosis of either chronic or acute hepatic insufficiency OR a total serum bilirubin greater than or equal to 2.0 mg/dL within 30 days prior to the start of surgery
10. Pre-existing RBC antibody that may make the provision of compatible study RBC components difficult
11. A positive cross match to S-303 treated RBC

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the study, consistent with the device-classification for the CE Mark registration, is the comparison of mean hemoglobin content per RBC component between the Test and Control groups. The hypothesis of interest is that the mean hemoglobin content is essentially equivalent, that any difference is of no clinical consequence, between the treatment groups.

E.5.1.1

Timepoint(s) of evaluation of this end point

Hemoglobin measurement will occur at production of each RBC unit. However, the comparison evaluation of mean hemoglobin content per RBC unit between the Test and Control groups will be performed at end of study, after a sufficient quantity of analyzable RBC units (at least 200 per treatment group) have been produced.

E.5.2

Secondary end point(s)

The secondary endpoints include assessments of relevant in vitro characteristics of RBC components that correlate with therapeutic efficacy:
•Proportion of RBC components that meet the EU guideline for hemoglobin content, hematocrit, and hemolysis at the end of storage
•Proportion of RBC components that have ATP levels of >2 micromol/L at 35 days of storage
•Proportion of RBC components that have plasma-free hemoglobin levels corresponding to < 0.8% hemolysis after 35 days of storage

E.5.2.1

Timepoint(s) of evaluation of this end point

In vitro measurements for characterization of RBC components will occur at the end of RBC storage (Day 35). However, evaluation of the proportion of RBC components that meet the EU Guidlines or pre-specified criteria will be performed at end of study.

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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)

Yes

E.8.2.2

Placebo

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Yes

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

Although the study ends for patients after a serum sample collection at the last visit on Day 90, the database-lock date will be used as the formal end-of-research date. Testing and data entry of test results of the last serum sample collected for the last patient is required as part of the study analysis and therefore justifies the database-lock date as the end-of-research date.

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 years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will continue their care with their primary care physicians according to local standard of care. No further treatment or care will be provided by the Sponsor once the patient completes the last visit for serum sample collection on Day 90.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-07-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-31

P. End of Trial
P.	End of Trial Status	Ongoing

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