Clinical Trials Register

Summary
EudraCT Number:	2017-004235-36
Sponsor's Protocol Code Number:	EWO-ISO-2017/2
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-08-09
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

2017-004235-36

A.3

Full title of the trial

A phase 4, randomized, open label multi-centre clinical study to evaluate efficacy of Isoprinosine® in female subjects with low-grade cervical dysplasia caused by HrHPV.

Randomizovaná, multicentrická, otevřená klinická studie fáze 4 k hodnocení účinnosti přípravku Isporinosine® u pacientek s cervikální dysplázií nízkého stupně, způsobenou vysoce rizikovými lidskými papilomaviry (HrHPV)

A.3.1

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

A phase 4, randomized, open label multi-centre clinical study to evaluate efficacy of Isoprinosine® in female subjects with low-grade cervical dysplasia caused by HrHPV.

A.4.1

Sponsor's protocol code number

EWO-ISO-2017/2

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	Ewopharma 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	EWOPHARMA 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	Ewopharma International s.r.o.
B.5.2	Functional name of contact point	Global medical affairs department
B.5.3	Address:
B.5.3.1	Street Address	Prokopa Veľkého 52
B.5.3.2	Town/ city	Bratislava
B.5.3.3	Post code	81104
B.5.3.4	Country	Slovakia
B.5.4	Telephone number	00421259429825
B.5.6	E-mail	e.salapova@ewopharma.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	Yes
D.2.1.1.1	Trade name	Isoprinosine®
D.2.1.1.2	Name of the Marketing Authorisation holder	Ewopharma International, s.r.o.
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.3.4	Pharmaceutical form	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	inosinum pranobexum
D.3.9.1	CAS number	36703-88-5
D.3.9.3	Other descriptive name	INOSINE PRANOBEX
D.3.9.4	EV Substance Code	SUB14214MIG
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	500
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

Low-grade cervical dysplasia caused by HrHPV

E.1.1.1

Medical condition in easily understood language

Low-grade cervical dysplasia caused by HrHPV

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

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

To evaluate whether the treatment with IAD contributes to the regression of low grade lesions ASC-US or LSIL (CIN I) cervical lesions associated with HrHPV infection.

E.2.2

Secondary objectives of the trial

Overall safety and tolerability of IAD.

To evaluate whether the treatment with IAD eliminates HrHPV (confirmed by negativity of COBAS test).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Female subjects aged between 18-47 years must be practicing an effective method of birth control as determined by the investigator (eg, oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or male partner with vasectomy or complete abstinence).
2. Cytologically confirmed ASC-US /LSIL, or histologically confirmed CIN1, or both within the last 12 months before screening V1 visit. In case the cytological examination was not done or was negative in pre-screening period, histologically confirmed CIN 1 will prevail.
3. Histologically confirmed CIN I stage by central laboratory.
4. Positivity on HrHPV by COBAS test from cervical sample
5. Negative pregnancy test from urine at screening (V1) and randomization (V2) visit
6. Signed Informed Consent Form

E.4

Principal exclusion criteria

1. Subjects with higher grade of squamous intraepithelial lesions ASC-H, HSIL (CIN II, CIN III).
2. Subjects using any investigational drug within 3 months before enrolment.
3. Subjects receiving immunosuppressive therapy (immunosuppressants, antitumor agents, etc.) at screening (V1) visit and throughout subjects’s participation in the study.
4. Subjects receiving treatment with xanthine oxidase inhibitors (allopurinol) or uricosuric agents, or treatment with thiazide diuretics (such as hydrochlorothiazide, chlorthalidone, and indapamide) or loop diuretics (such as furosemide, torsemide, and ethacrynic acid) at screening (V1) visit and throughout subjects’s participation in the study.
5. Signs or symptoms of acute vaginal/cervical/pelvic infection at screening (V1) and randomization (V2) visit.
6. History of previous prophylactic HPV vaccination
7. Subjects with renal dysfunction (creatinine clearance <50 mL/min) in medical history, or increase of serum creatinine at screening (V1) visit assessed as clinically significant by investigator.
8. Subjects receiving treatment with AZT (zidovudine) at screening (V1) visit and throughout subjects’s participation in the study.
9. Subjects with known hypersensitivity to IAD.
10. Pregnant or lactating/breastfeeding female subjects.
11. Subjects with a history of gout, urolithiasis and clinically significant hyperuricemia assessed by investigator at the V1.
12. HIV positive subjects
13. Subjects with liver disorder (severe liver function impairment, AST and ALT value greater than 3 times the upper limit of normal

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects without LSIL (CIN I) lesion in 6 months after randomization.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months after randomisation

E.5.2

Secondary end point(s)

1. The overall safety and tolerability of IAD as assessed by evaluating of adverse events and serious adverse events (SAE) reported during the course of the study.
2. Proportion of subjects with HrHPV negative cervical samples assessed by COBAS test between IAD treatment group and control group.

E.5.2.1

Timepoint(s) of evaluation of this end point

End of study visit

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

E.8.2.3

Other

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

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

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:

166

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

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

166

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

166

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 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

2018-09-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-09-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-09-02

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