Clinical Trials Register

Summary
EudraCT Number:	2013-001205-84
Sponsor's Protocol Code Number:	PCG-4/UCR
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-08-08
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 - BfArM

A.2

EudraCT number

2013-001205-84

A.3

Full title of the trial

Randomized, double-blind, double-dummy, placebo-controlled, Phase III clinical trial on the efficacy and safety of a 48-weeks treatment with gastro-resistant phosphatidylcholine (LT-02) versus placebo versus mesalamine for maintenance of remission in patients with ulcerative colitis

Randomisierte, doppelblinde, double-dummy, plazebo-kontrollierte klinische Phase III Studie zur Evaluierung der Wirksamkeit und Sicherheit einer 48-wöchigen Therapie mit LT-02 (magensaftresistentes Phosphatidylcholin-Granulat) vs. Plazebo vs. Mesalazin zur Erhaltung der Remission bei Patienten mit Colitis ulcerosa

A.3.1

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

LT-02 (gastro-resistant phosphatidylcholine granules) vs. placebo vs. mesalamine for maintenance of remission in
patients with ulcerative colitis

A.3.2

Name or abbreviated title of the trial where available

Phosphatidylcholine (LT-02) vs. placebo vs. mesalamine for maintenance of remission in UC

A.4.1

Sponsor's protocol code number

PCG-4/UCR

A.5.4

Other Identifiers

Name:

Acronym

Number:

PROTECT-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	Dr. Falk Pharma GmbH
B.1.3.4	Country	Germany
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	Dr. Falk Pharma GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ICON Clinical Research GmbH
B.5.2	Functional name of contact point	EvaVörös
B.5.3	Address:
B.5.3.1	Street Address	Szépvölgyi út 39.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1037
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+36703300472
B.5.5	Fax number	+361778 9223
B.5.6	E-mail	eva.voros@iconplc.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	gastro-resistant phosphatidylcholine granules
D.3.2	Product code	LT-02
D.3.4	Pharmaceutical form	Gastro-resistant granules
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	Phosphatidylcholine
D.3.9.1	CAS number	97281-47-5
D.3.9.2	Current sponsor code	LT-02
D.3.9.3	Other descriptive name	SOYBEAN PHOSPHATIDYLCHOLINE
D.3.9.4	EV Substance Code	SUB33201
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	800
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.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	Salofalk Granu-Stix 500 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Dr. Falk Pharma
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.3.4	Pharmaceutical form	Gastro-resistant granules
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	MESALAZINE
D.3.9.1	CAS number	89-57-6
D.3.9.4	EV Substance Code	SUB08782MIG
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Gastro-resistant granules
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Gastro-resistant granules
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

Maintenance of remission in ulcerative colitis (UC)

E.1.1.1

Medical condition in easily understood language

Maintenance of remission in ulcerative colitis (UC)

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045365
E.1.2	Term	Ulcerative colitis
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary:
To prove the superiority of a 48-weeks treatment with 3.2 g/day delayed-release phosphatidylcholine (LT-02) versus placebo for the maintenance of remission in patients with ulcerative colitis (UC)

E.2.2

Secondary objectives of the trial

Secondary:
To study safety and tolerability in the form of adverse events (AEs) and laboratory parameters,
To assess patients’ quality of life.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Open-label sub-study:
• To re-induce and/or maintain remission of UC in patients who prematurely dropped-out due to lack of efficacy or who completed the double-blind phase still being in remission.

E.3

Principal inclusion criteria

Inclusion criteria for DB maintenance phase:
1. Signed informed consent,
2. Men or women, 18 to 70 years of age,
3. Historically confirmed diagnosis of UC by endoscopy and histology,
4. Patients being in remission at baseline,
5. Negative pregnancy test in females of childbearing potential at baseline visit,
6. Women of child-bearing potential have to apply during the entire duration of the trial a highly effective method of birth control, which is defined as those which result in a low failure rate (i.e., less than 1% per year) when used constantly and correctly.

E.4

Principal exclusion criteria

Exclusion criteria for DB maintenance phase:
1. Crohn's disease, indeterminate colitis, ischemic colitis, radiation colitis, microscopic colitis (i.e., collagenous colitis and lymphocytic colitis), diverticular disease associated colitis,
2. Toxic megacolon or fulminant colitis,
3. Colon resection,
4. Malabsorption syndromes,
5. Celiac disease,
6. Bleeding hemorrhoids,
7. Other inflammatory or bleeding disorders of the colon and intestine, or diseases that may cause diarrhea or gastrointestinal bleeding,
8. History or presence of ischemic heart disease, myocardial infarction, peripheral arterial disease, ischemic stroke, or transient ischemic attack,
9. Any severe concomitant renal, endocrine, or psychiatric disorder, which in the opinion of the investigator might have an influence on the patient’s compliance or the interpretation of the results,
10. Any relevant known systemic disease (e.g., AIDS, active tuberculosis),
11. Severe co-morbidity substantially reducing life expectancy,
12. History of cancer in the last five years,
13. Abnormal hepatic function at the screening visit), liver cirrhosis,
14. Abnormal renal function at the screening visit,
15. Either HbA1c ≥6.5% (≥48 mmol/mol) at baseline visit, OR HbA1c >5.6% (38 mmol/mol) AND fasting blood glucose ≥100 mg/dl (≥5.6 mmol/l) at baseline visit,
16. Patients with known hypersensitivity to soy,
17. Known intolerance/hypersensitivity to Investigational Medicinal Product (IMP: LT-02 or mesalamine),
18. Treatment with steroids (oral, inhalative, or intravenous [IV]), cyclosporine or tacrolimus within last 4 weeks prior to randomization,
19. Treatment with methotrexate within last 6 weeks prior to randomization,
20. Treatment with TNF-alpha-antagonists, azathioprine, 6-mercaptopurine, or anti-integrin therapy within last 8 weeks prior to randomization,
21. Treatment with rectal mesalamine or corticosteroid formulations within last 2 weeks prior to randomization,
22. Treatment with other investigational drug within last 12 weeks prior to randomization except LT-02,
23. Concomitant treatment with coumarins (e.g., phenprocoumon),
24. Unwillingness to undergo endoscopy with biopsy sampling at end of treatment (EOT)/withdrawal visit of this study,
25. Clinical suspicion of addiction to alcohol or drugs,
26. Existing or intended pregnancy or breast-feeding,
27. Subjects deemed by the investigator to be unlikely to comply with the protocol requirements, instructions and study-related restrictions; e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study,
28. Participation in another clinical trial within the last 30 days prior to baseline visit (except for the Phase III study PCG-2/UCA), simultaneous participation in another clinical trial, or previous participation in this trial and having received IMP.

E.5 End points

E.5.1

Primary end point(s)

Percentage of patients who are relapse-free and are not a treatment failure after 48 weeks of treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

After week 48 (LOCF) of double-blind treatment phase

E.5.2

Secondary end point(s)

• Mean change from baseline in the total mDAI at V6/EOT.
• Time to relapse or discontinuation,
• Time to relapse.

E.5.2.1

Timepoint(s) of evaluation of this end point

After week 48 (LOCF) of double-blind treatment phase

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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

Yes

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

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

Austria

Belgium

Czech Republic

Germany

Hungary

Israel

Latvia

Lithuania

Netherlands

Poland

Russian Federation

Slovakia

Switzerland

Ukraine

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

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:

360

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

150

F.4.2

For a multinational trial

F.4.2.1

In the EEA

250

F.4.2.2

In the whole clinical trial

400

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)

Open-label extension (OLE) phase: Patients completing the DB-phase without experiencing a relapse and those patients who have achieved a clinical response in the OLRI phase can receive OLE-treatment for up to 48 weeks.
Open-label re-induction (OLRI) phase: Patients prematurely discontinued from the DB-phase due to lack of efficacy will be offered an OL re-induction for up to 12 weeks.
Follow-up phase: Patients will be followed-up 4 weeks after their last treatment visit in the DB or OL

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

2014-10-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-01-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-10-05

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