Clinical Trials Register

Summary
EudraCT Number:	2014-000377-40
Sponsor's Protocol Code Number:	MST-188-07
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-09-12
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

Czechia - SUKL

A.2

EudraCT number

2014-000377-40

A.3

Full title of the trial

Evaluation of MST-188 in Acute Lower Limb Ischemia: A Phase 2 Randomized Double-Blind, Placebo-Controlled, Multi-Center Clinical Trial Evaluating the Safety and Efficacy Of MST-188 in Subjects with Acute Lower Limb Ischemia Receiving Catheter-Directed Recombinant Tissue Plasminogen Activator

Hodnocení přípravku MST-188 v léčbě akutní ischemie dolních končetin: randomizované, dvojitě zaslepené, placebem kontrolované multicentrické klinické hodnocení fáze II hodnotící bezpečnost a účinnost přípravku MST-188 u subjektů s akutní ischemií dolních končetin, kterým je katétrem cíleně podáván rekombinantní tkáňový aktivátor plazminogenu

A.3.1

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

Evaluation of MST-188 in Acute Lower Limb Ischemia

Hodnocení přípravku MST-188 v léčbě akutní ischemie dolních končetin

A.3.2

Name or abbreviated title of the trial where available

Evaluation of MST-188 in Acute Lower Limb Ischemia

A.4.1

Sponsor's protocol code number

MST-188-07

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02093468

A.5.4

Other Identifiers

Name:

IND Number

Number:

31246

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	Mast Therapeutics, Inc.
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	Mast Therapeutics, 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	Theradex (Europe) Ltd
B.5.2	Functional name of contact point	Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	2nd Floor, The Pinnacle, Station Way
B.5.3.2	Town/ city	Crawley
B.5.3.3	Post code	RH10 1JH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441293510319
B.5.5	Fax number	+441293510322
B.5.6	E-mail	mmoores@theradex.co.uk

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	MST-188 (purified poloxamer 188) Injection
D.3.2	Product code	MST-188
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	Purified poloxamer 188
D.3.9.2	Current sponsor code	Purified poloxamer 188
D.3.9.3	Other descriptive name	POLOXAMER 188
D.3.9.4	EV Substance Code	SUB16038MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
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	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 Lower Limb Ischemia

E.1.1.1

Medical condition in easily understood language

Acute Lower Limb Ischemia

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	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10066920
E.1.2	Term	Leg ischemia
E.1.2	System Organ Class	100000004866

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

- To evaluate the safety and efficacy of MST-188 in subjects receiving catheter-directed recombinant tissue plasminogen activator (rt-PA) for acute lower limb ischemia, and
- To evaluate whether MST-188 results in more rapid thrombolysis and tissue perfusion

E.2.2

Secondary objectives of the trial

- To assess the clinically-meaningful benefit of therapy, tabulating outcomes such as duration of thrombolytic therapy, amputation-free survival, target limb re-interventions, and
- To assess the need for endovascular or open surgical re-interventions.
These objectives will be measured through up to 90 days of follow-up.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written documentation of informed consent
2. Age ≥30 and <80 years
3. Symptoms consistent with acute ischemia in the target lower limb of ≤14 days’ duration and classified as Rutherford Category IIa or IIb
4. Subject is hospitalized or in the process of admission for the treatment of acute limb ischemia (ALI)
5. Angiographic confirmation of thrombotic lower limb arterial occlusion ≥10 cm in length
6. Planned recombinant tissue plasminogen activator (rt-PA) intra-arterial, catheter-directed thrombolytic therapy
7. Target lower limb transcutaneous oxygen tension (TcPO2) ≤40 mmHg
8. Ankle-brachial index (ABI) ≤0.60 in the target lower limb or, if vessels are incompressible as defined by ABI ≥1.40 then a toe-brachial index (TBI) ≤0.50
9. If sexually active, the subject agrees to use reliable contraception while participating in this study and for at least 30 days after discontinuation of blinded study drug infusion
10. If the subject is female and of child-bearing potential, must have negative pregnancy test (urine or serum)

E.4

Principal exclusion criteria

1. Prosthetic bypass graft occlusion within 1 month of implantation or autogenous graft occlusion within 6 months of placement
2. Prior major amputation in the target limb
3. Inability to place a guidewire to the distal end of the occluding thrombus and position an infusion catheter into the thrombus
4. Thrombotic occlusion limited to the infrapopliteal arteries
5. Occlusion of all of the following tibial arteries on the baseline angiogram: anterior tibial, posterior tibial and peroneal
6. Thrombosis of or embolization deemed to be from a popliteal aneurysm by investigator
7. Motor loss with inability to dorsiflex the foot
8. Rhabdomyolysis and/or myoglobinuria
9. Embolization as the suspected cause of the arterial occlusion
10. Treatment with a thrombolytic agent within the last 48 hours
11. Subject has a known or suspected bleeding diathesis
12. Intracranial or spinal surgery or severe intracranial trauma within the last 3 months
13. History of hemorrhagic stroke, known intracranial neoplasm, aneurysm, or arteriovenous malformation
14. Thrombotic or embolic stroke within 6 months or transient ischemic attack within 3 months
15. Major surgery, intraocular surgery, organ biopsy, lumbar puncture, or puncture of an incompressible artery in the last 10 days
16. New York Heart Association Class IV congestive heart failure
17. Active gastrointestinal or other active organ bleeding
18. Uncontrolled arterial hypertension with systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg
19. Hemoglobin <8 g/dL
20. Subject’s international normalized ratio (INR) >1.7 and unable to be corrected prior to gaining arterial access
21. Subject has platelet count <75,000/mm3
22. Subject has hepatic dysfunction defined by alanine aminotransferase (ALT) >3-fold the institution’s upper limit of normal
23. Subject has a serum creatinine value >1.5 mg/dL or is on dialysis
24. Subject is pregnant or nursing
25. Current vascular graft infection
26. Subject is already hospitalized for any condition other than acute lower limb ischemia in the target limb
27. Subject is currently receiving another investigational drug or has received any investigational drug within 30 days prior to randomization
28. Any contraindications for receiving rt-PA, anticoagulants, or contrast media
29. Subject is otherwise not an appropriate study subject, in the Investigator's judgment
30. Subject has been previously randomized in the present trial or any prior MST-188 clinical trial

E.5 End points

E.5.1

Primary end point(s)

1. Change in TcPO2
2. Change in TcPO2 as measured by area under the curve (AUC) for change in TcPO2
3. Volume of thrombus dissolved after start of MST-188 infusion as assessed by angiography
4. Change in ABI and TBI (or TBI only in subjects with incompressible vessels)

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Baseline, 8 hours, 12 hours, and 24 hours
2. Baseline, 8 hours, 12 hours, and 24 hours
3. At approximately 8 hours and 24 hours
4. Baseline, 8 hours, 12 hours, and 24 hours

E.5.2

Secondary end point(s)

1. Time to reperfusion, measured from the start of MST-188 infusion to attainment of specific increases in TcPO2
2. Open surgery-free survival
3. Patency of the target vessel
4. Freedom from repeat thrombolysis of the target vessel
5. Freedom from major surgery in the target limb
6. Freedom from major amputation
7. All-cause mortality

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Attainment of specific increases in TcPO2
2. Over 30 days and 90 days
3. Over 30 days and 90 days
4. Over 90 days
5. Over 90 days
6. Over 90 days
7. Over 90 days

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

Yes

E.6.7

Pharmacodynamic

Yes

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

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Proof-of-concept trial

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

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

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

Czech Republic

Hungary

Poland

United States

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.1.1.1

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)

Standard of Care

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

2015-03-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-02-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2015-08-13

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