Clinical Trials Register

Summary
EudraCT Number:	2010-023129-39
Sponsor's Protocol Code Number:	MP4OX-10-TRA-205
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-03-02
Trial 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

Italy - Italian Medicines Agency

A.2

EudraCT number

2010-023129-39

A.3

Full title of the trial

A multi-center, randomized, double-blind, controlled study to evaluate the safety and efficacy of MP4OX treatment, in addition to standard treatment, in severely injured trauma patients with lactic acidosis due to hemorrhagic shock

Studio controllato multicentrico, randomizzato, in doppio cieco per valutare la sicurezza e l'efficacia del trattamento con MP4OX, piu' il trattamento standard, in pazienti gravemente traumatizzati che presentano acidosi lattica a seguito dello shock emorragico

A.3.1

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

This study will assess the safety and effectiveness of MP4OX when added to standard treatment for trauma patients who are severely injured and bleeding

Lo studio valutera' sicurezza ed efficacia di MP4OX quando somministrato in aggiunta alla terapia standard in pazienti gravemente traumatizzati e con emoraggie.

A.4.1

Sponsor's protocol code number

MP4OX-10-TRA-205

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01262196

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	SANGART
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	Sangart Inc.
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	Sangart Inc.
B.5.2	Functional name of contact point	Chief Medical Officer
B.5.3	Address:
B.5.3.1	Street Address	6175 Lusk Boulevard
B.5.3.2	Town/ city	San Diego
B.5.3.3	Post code	CA 92121
B.5.3.4	Country	United States
B.5.4	Telephone number	+1.858.344.4774
B.5.5	Fax number	+1 858 450 2499
B.5.6	E-mail	fbooth@sangart.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	Emoglobina ossigenata pegilata
D.3.2	Product code	MP4OX
D.3.4	Pharmaceutical form	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	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	MP4OX
D.3.9.3	Other descriptive name	Polyethylene Glycol Human Hemoglobin Conjugate
D.3.9.4	EV Substance Code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	43
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	Yes
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.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.2.1.1.2	Name of the Marketing Authorisation holder	B. Braun Melsungen AG
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.4	Pharmaceutical form	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	NA
D.3.9.1	CAS number	0
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	SODIUM CHLORIDE SOLUTION 0.9%
D.3.9.4	EV Substance Code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	g/l gram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	9
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

severely injured trauma patients with lactic acidosis due to hemorrhagic shock

pazienti gravemente traumatizzati che presentano acidosi lattica a seguito dello shock emorragico

E.1.1.1

Medical condition in easily understood language

trauma patients who are severely injured and bleeding

pazienti traumatizzati gravemente feriti e con emoraggie

E.1.1.2

Therapeutic area

Diseases [C] - Injuries, poisonings, and occupational diseases [C21]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10023676
E.1.2	Term	Lactic acidosis
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

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	10050841
E.1.2	Term	Hemorrhagic shock
E.1.2	System Organ Class	10047065 - Vascular 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

The primary objective is to evaluate the safety and efficacy of 250 mL MP4OX treatment compared to 250 mL of normal saline solution plus replacement doses if continued hemorrhage, in addition to standard treatment, in severely injured trauma patients with lactic acidosis due to hemorrhagic shock

L'obiettivo principale è valutare la sicurezza e l'efficacia del trattamento con 250ml di MP4OX in confronto a 250 ml di soluzione fisiologica normale più dosi di rimpiazzo se continua l’emorragia, in aggiunta al trattamento standard, in pazienti gravemente traumatizzati che presentano acidosi lattica a seguito dello shock emorragico

E.2.2

Secondary objectives of the trial

---

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1)Informed consent obtained before any study-related activities (study-related activities are any procedure that would not have been performed as standard of care for the patient) 2)Trauma injury (blunt and/or penetrating) resulting in lactic acidosis due to hemorrhagic shock 3)Acidosis (blood lactate level ≥ 5 mmol/L; equivalent to 45 mg/dL) arterial or venous

1) Consenso informato ottenuto il prima di qualsiasi attività associata allo studio; 2) Lesione traumatica (netta e/o penetrante) che porta a acidosi lattica secondaria allo shock emorragico; 3) Acidosi (livello di lattato nel sangue ≥ 5 mmol/l; equivalente a 45 mg/dl ) arteriosa o venosa

E.4

Principal exclusion criteria

1)Massive injury incompatible with life 2)Normalization of lactate prior to dosing (≤ 2.2mmol/L) 3)Patients with evidence of severe traumatic brain injury as defined by ANY one of the following: a)Known non-survivable head injury or open brain injury b)Glasgow Coma Score (GCS) = 3, 4 or 5 c)Known AIS (head region) ≥ 4 shown by an appropriate imaging methodology d)Contemplated CNS surgery e)Abnormal physical exam indicative of severe CNS or any spinal cord injury above T5 level 4)Cardiac arrest prior to randomization 5)Age below the legal age for consenting 6)Estimated time from injury to randomization> 4 hours 7)Estimated time from hospital admission to randomization > 2 hours 8)Known pregnancy 9)Use of any oxygen carrier other than RBCs 10)Known previous participation in this study 11)Professional or ancillary personnel involved with this study 12)Known receipt of any investigational drug(s) within 30 days prior to study

1) Lesione massiva incompatibile con la vita; 2) Normalizzazione del lattato prima della somministrazione (≤2,2mmol/l); 3) Pazienti con evidenze di grave lesione traumatica cerebrale come definito da UNA QUALSIASI delle seguenti condizioni: - Trauma cranico o ferita aperta del cervello che notoriamente hanno esito fatale, - Glasgow Coma Score (GCS) = 3, 4 o 5, - Noto AIS (regione cranica) ≥ 4 mostrato da un’appropriata tecnica di imaging, - Chirurgia del SNC contemplata, - Anomalie all’esame obiettivo indicative di grave lesione del SNC o qualsiasi lesione spinale al di sopra del livello T5; 4) Arresto cardiaco prima della randomizzazione; 5) Età inferiore alla maggiore età per fornire il consenso alla partecipazione; 6) Tempo previsto dal momento della lesione alla randomizzazione > 4 ore; 7) Tempo previsto dal momento lesione alla randomizzazione > 2 ore; 8)Gravidanza nota; 9)Uso di qualsiasi trasportatore di ossigeno diverso dagli RBC; 10) Nota partecipazione precedente a questo stesso studio; 11) Personale professionale o ausiliario coinvolto in questo studio; 12) Avere notoriamente ricevuto qualsiasi farmaco in fase investigativa entro i 30 giorni che precedono lo studio

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the proportion of patients discharged from hospital through day 28 and alive at the Day 28 Follow up visit

L’endpoint primario di efficacia è la percentuale di pazienti dimessi dall’ospedale fino al giorno 28 e vivi alla visita di Follow up al Giorno 28

E.5.1.1

Timepoint(s) of evaluation of this end point

day 28

giorno 28

E.5.2

Secondary end point(s)

---

E.5.2.1

Timepoint(s) of evaluation of this end point

---

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)

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)

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Brazil

Colombia

Israel

New Zealand

Singapore

South Africa

Switzerland

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

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 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

Number of subjects for this age range:

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:

340

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2012-03-02.

Yes

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients eligible for randomization must be in hemorrhagic shock, with evidence of lactic acidosis within 2 hours after arrival to the hospital and within 4 hours of estimated time of injury

I pazienti eligibili per la randomizzazione devono essere in shock emorragico con acidosi lattica entro 2 ore dall'arrivo in ospedale ed entro 4 ore dal momento stimato dell'incidente

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

220

F.4.2.2

In the whole clinical trial

360

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)

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

2012-05-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-01-11

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

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