Clinical Trials Register

Summary
EudraCT Number:	2016-003078-41
Sponsor's Protocol Code Number:	MUC-2/16
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:	2016-09-15
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

Czechia - SUKL

A.2

EudraCT number

2016-003078-41

A.3

Full title of the trial

Reduction of post-traumatic systemic inflammatory response by Phlogenzym® using total hip replacement as a model.

Snížení posttraumatické systémové zánětlivé odpovědi užitím Pholgenzymu® u pacientů po totální náhradě kyčelního kloubu jako modelové situaci

A.3.1

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

Influence of treatment with Phlogenzym® on recovery after total hip replacement as a model.

A.4.1

Sponsor's protocol code number

MUC-2/16

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	MUCOS Pharma CZ s.r.o.
B.1.3.4	Country	Czech Republic
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	Mucos Pharma CZ s.r.o.
B.4.2	Country	Czech Republic
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	MUCOS Pharma CZ
B.5.2	Functional name of contact point	Clinical department
B.5.3	Address:
B.5.3.1	Street Address	Uhříněveská 448
B.5.3.2	Town/ city	Průhonice
B.5.3.3	Post code	252 43
B.5.3.4	Country	Czech Republic
B.5.4	Telephone number	+420267 750 003
B.5.6	E-mail	akocar@mucos.cz

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	Yes
D.2.1.1.1	Trade name	Phlogenzym
D.2.1.1.2	Name of the Marketing Authorisation holder	MUCOS Pharma GmbH Co.KG
D.2.1.2	Country which granted the Marketing Authorisation	Czech Republic
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	Phlogenzym
D.3.4	Pharmaceutical form	Coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Trypsin
D.3.9.1	CAS number	9002-07-7
D.3.9.3	Other descriptive name	TRYPSIN
D.3.9.4	EV Substance Code	SUB12616MIG
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	48
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Bromelain
D.3.9.1	CAS number	37189-34-7
D.3.9.3	Other descriptive name	BROMELAIN
D.3.9.4	EV Substance Code	SUB22009
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	90
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RUTOSIDE
D.3.9.1	CAS number	250249-75-3
D.3.9.4	EV Substance Code	SUB10407MIG
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	100
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.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	Coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Total hip replacement

E.1.1.1

Medical condition in easily understood language

Total hip replacement

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

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 objective of the study is to explore the validity and clinical feasibility of methods for assessment of perioperative efficacy of Phlogenzym in terms of symptoms of systemic (CRP, hemocoagulation) and local inflammation and short- and mid-term course of rehabilitation, with the aim to select the primary and secondary endpoints for an intended confirmatory study.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. The patient has primary diagnosis of Non-Inflammatory Degenerative Joint Disease.
2. The patient has signed an Informed Consent Form, approved by the EC and CA.
3. The patient is a male or non-pregnant female age 50 years or older at time of arthroplasty.
4. The patient is a candidate for a primary cementless total hip replacement
via anterolateral approach in spinal (subarachnoidal) anesthesia.
5. There are no contraindications for planned concomitant medication.
6. The patient is willing and able to comply with postoperative scheduled clinical evaluations and rehabilitation.
7. The patient agrees to abstain from smoking from the signing of the informed consent till the discharge from the hospital.
8. Anticipated uncomplicated operation course as per Investigator´s judgment.
9. Female subjects in the fertile ageWomen of childbearing potential, unless practicing sexual abstinence, must take adequate contraceptive measures: a barrier method in combination with spermicide or per-oral contraception or IUD with an exception of women who are post-menopausal or are not of child bearing potential. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

E.4

Principal exclusion criteria

1. The patient has a Body Mass Index (BMI) ≤ 20 and ≥35.
2. The patient has an active or suspected latent infection in or about the affected hip joint at the time of the implantation.
3. The patient has a baseline CRP value > 6 mg/l.
4. The patient has been a tobacco smoker for any time within the last 12 months.
5. The patient has a neuromuscular or neurosensory deficiency, which limits the validity of the assessment procedures.
6. The patient is diagnosed with a systemic disease (e.g. rheumathoid arthritis, lupus erythematosus) or a metabolic disorder (e.g. Paget's Disease) leading to progressive bone deterioration.
7. The patient is immunologically suppressed or receiving steroids in excess of normal physiological requirements (at least 30 days before study).
8. Planned mini-incision or other than anterolateral approach operation.
9. The patient requires revision operation of a previously implanted total hip replacement or hip fusion to the affected joint.
10. The patient has a known sensitivity to device materials or Phlogenzym® or Placebo.
11. Pregnancy or nursing.
12. Insulin dependent DM.
13. Contraindication of Xarelto® or history of intolerance of Xarelto®.®; otherwise, there is no prohibited concomitant medication.
14. Participation or planned participation in another clinical study.
15. Inborn or acquired hemocoagulation disorders (hemophilia, severe liver dysfunction).
16. The patient is on hemodialysis

E.5 End points

E.5.1

Primary end point(s)

1. C-reactive protein in serum, AUC from Day 1 through Day 7 following operation,
2. values of selected hemocoagulation parameters in plasma (anti Xa, Quick, APTT, fibrinogen),
3. blood transfusion volume during operation,
4. blood transfusion volume after operation,
5. cumulative Redon drain discharge volume till 48 hours after operation,
6. thigh and calf circumference, AUC from Day 1 through Day 7 following operation,
7. body temperature in axilla, AUC from Day 1 through Day 7 following operation,
8. local pain at rest, self-rated on the 10 cm Visual Analogue Scale (VAS), AUC from Day 1 through Day 7after operation,
9. knee extension strength, on Day 5 and Day 7 after operation,
10. frequency of any rescue analgesic medication through Day 1 to Day 7 after operation.

E.5.1.1

Timepoint(s) of evaluation of this end point

Postoperative period: 1 till 7 days postoperative

E.5.2

Secondary end point(s)

1. thigh and calf circumference, assessments on Day 7, Day 14, Day 28 and Day 42 after operation,
2. Harris Hip Score (HHS), assessments on Day 7, Day 14, Day 21, Day 28 and Day 42,
3. performance in timed Up&Go Test (TUG), assessments on Day 7, Day 14, Day 21, Day 28 and Day 42,
4. knee extension strength, assessments on Day 7, Day 14, Day 21, Day 28 and Day 42,
5. local pain at rest (VAS), assessments on Day 7, Day 14, Day 21, Day 28 and Day 42,
6. cumulative consumption of the rescue analgesics (number of doses) from Day 7 till Day 42,
7. cumulative number of analgesics-free days from Day 7 till Day 42,
8. Clinical Global Impression of Change – patient’s and Investigator’s assessment of change from the first postoperative day done on Day 7, Day 14, Day 21, Day 28 and Day 42.

E.5.2.1

Timepoint(s) of evaluation of this end point

Rehabilitation period: 7 till 42 days postoperative

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

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

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Pacienti budou léčeni dle běžné praxe a navíc budou dostávat Phlogenzym nebo placebo

Add-on – Study subjects receive standard treatment with addition of either Phlogenzym or placebo

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

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

Last visit of the last patient

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

F.3.3.2

Women of child-bearing potential using contraception

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.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)

None

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

2018-11-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-11-23

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-10-15

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