Clinical Trials Register

Summary
EudraCT Number:	2020-005051-20
Sponsor's Protocol Code Number:	HISTIOGEN
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-01-12
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2020-005051-20

A.3

Full title of the trial

Determination Of Molecular Status And Benefit Of Use Fludeoxyglucose (18F-FDG) In PET/CT imagining In Juvenile Patients With Histiocytosis

Oszacowanie profilu molekularnego oraz przydatności i bezpieczeństwa użycia fluorodeoksyglukozy (18F-FDG) w obrazowaniu PET-TK u małoletnich pacjentów z rozrostami z komórek histiocytarnych.

A.3.1

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

Examination of the molecular profile in adolescent patients with histiocytic cell hyperplasia, and if a specific mutation is detected, its monitoring.
Determination clinical benefit of use fludeoxyglucose (18F-FDG) in PET/CT imagining in with histiocytosis

Zbadanie profilu molekularnego u małoletnich pacjentów z rozrostami z komórek histiocytarnych, a w przypadku wykrycia konkretnej mutacji jej monitorowanie.
Określenie klinicznej korzyści stosowania fludeoksyglukozy (18F-FDG) w obrazowaniu PET / TK z histiocytozą

A.3.2

Name or abbreviated title of the trial where available

HISTIOGEN

A.4.1

Sponsor's protocol code number

HISTIOGEN

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	Institute of Mother and Child
B.1.3.4	Country	Poland
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Medical Research Agency
B.4.2	Country	Poland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Institute of Mother and Child
B.5.2	Functional name of contact point	Department of Oncology and Surgical
B.5.3	Address:
B.5.3.1	Street Address	Kasprzaka 17a
B.5.3.2	Town/ city	Warsaw
B.5.3.3	Post code	01-211
B.5.3.4	Country	Poland
B.5.4	Telephone number	482232 77 205
B.5.6	E-mail	klinika.onkologii@imid.med.pl

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	GLUNEKTIK
D.2.1.1.2	Name of the Marketing Authorisation holder	Synektik Pharma Sp. z. o.o.
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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	GLUNEKTIK
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	FLUDEOXYGLUCOSE (18F)
D.3.9.1	CAS number	105851-17-0
D.3.9.2	Current sponsor code	fluorodeoksyglukoza
D.3.9.3	Other descriptive name	18F-FDG
D.3.9.4	EV Substance Code	SUB07680MIG
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/ml megabecquerel(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	200 to 22000
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	Yes
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	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	SYNEKTIK
D.2.1.1.2	Name of the Marketing Authorisation holder	Synektik Pharma Sp. z. o.o.
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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	SYNEKTIK
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	Fludeoxyglucose (18F)
D.3.9.1	CAS number	105851-17-0
D.3.9.2	Current sponsor code	fluorodeoksyglukoza
D.3.9.3	Other descriptive name	18F-FDG
D.3.9.4	EV Substance Code	SUB07680MIG
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/ml megabecquerel(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	200 to 22000
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	Yes
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

histiocytic cell proliferation

rozrost komórek histiocytarnych

E.1.1.1

Medical condition in easily understood language

Neoplasm derived from histiocyte

Nowotwór pochodzący z histiocytów

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10069698
E.1.2	Term	Langerhans' cell histiocytosis
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10078782
E.1.2	Term	Langerhans cell sarcoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10060801
E.1.2	Term	Erdheim-Chester disease
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10063397
E.1.2	Term	Rosai-Dorfman syndrome
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Determination of molecular status and benefit and safety of use fludeoxyglucose (18-FDG) in PET/CT imagening in juvenile patients with histiocytosis.

Oszacowanie profilu molekularnego oraz przydatności i bezpieczeństwa użycia fluorodeoksyglukozy (18F-FDG) w obrazowaniu PET-TK u małoletnich pacjentów z rozrostami z komórek histiocytarnych.

E.2.2

Secondary objectives of the trial

1. Evaluation of clinical benefit and safety of use fludeoxyglucose (18F-FDG) in PET/CT imagening in juvenile patients with histiocytosis.
2. To determine the frequency of BRAF mutation in juvenile patients in Poland.
3. To determine the frequency of other mutations in juvenile patients in Poland.
4. To determine the rate of occurrence of mutations in ctDNA at different parts of treatment and follow-up.
5. To evaluate the diagnostic usefulness of the occurrence of mutations in ctDNA as a prognostic factor compared with other recognized factors.
6. Establishing of an immortalized cell line.

1. Ocena przydatności i bezpieczeństwa użycia fluorodeoksyglukozy (18F-FDG) w obrazowaniu PET-TK u małoletnich pacjentów z rozrostami z komórek histiocytarnych.
2. Oszacowanie częstości występowania mutacji w genie BRAF w populacji polskiej małoletnich chorych z rozrostami z komórek histiocytarnych.
3. Oszacowanie częstości występowania innych mutacji niż BRAF w populacji polskiej małoletnich chorych z rozrostami z komórek histiocytarnych.
4. Ocena obecności mutacji w wolnokrążącym DNA (ctDNA) na różnych etapach procesu terapeutycznego.
5. Ocena obecności mutacji w wolnokrążącym DNA (ctDNA) jako czynnika rokowniczego w porównaniu z innymi, uznanymi czynnikami.
6. Wyprowadzenie unieśmiertelnionej linii komórkowej.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient under 18 years of age at the time of inclusion.
2. Histopatologically confirmed or suspected histiocytosis (based on prior test results).
3. Signing of informed consent for trial participation according with current legal regulations.

1. Wiek poniżej 18rż w momencie kwalifikacji do badania
2. Potwierdzony badaniem histopatologicznym rozrost z komórek histiocytarnych lub podejrzenie takiego rozrostu na podstawie dotychczas wykonanych badań.
3. Udzielenie pisemnej, świadomej zgody na udział w badaniu przed rozpoczęciem procedur objętych protokołem badania zgodnie z aktualnymi regulacjami prawnymi.

E.4

Principal exclusion criteria

1. Lack of inclusion criteria.
2. Pregnancy.
3. Other acute or persistent disorders, behaviors or abnormal laboratory test results, which might increase the risk related to the participation in this clinical trial or to taking the study drug, or which might influence the interpretation of the study results, or which, in the investigator’s opinion, disqualify a patient from participating in the trial.

1. Niespełnienie któregokolwiek z kryteriów włączenia.
2. Ciąża.
3. Inne ostre lub przewlekłe schorzenia, zachowania lub nieprawidłowe wartości badań laboratoryjnych, które mogą zwiększać ryzyko związane z uczestnictwem w niniejszym badaniu klinicznym lub mogą wpływać na interpretację wyników badania, lub też, w opinii badacza, mogą sprawiać, że pacjent nie powinien być włączany do badania.

E.5 End points

E.5.1

Primary end point(s)

EFS – (event-free survival).

• EFS – (event-free survival) czas przeżycia wolnego od zdarzeń.

E.5.1.1

Timepoint(s) of evaluation of this end point

Interim analyzes were planned after the enrollment of 50 patients.

Zaplanowano analizy pośrednie po włączeniu 50 pacjentów.

E.5.2

Secondary end point(s)

Secondary endpoints:
• PFS (Progression-Free Survival),
• OS (Overall Survival),
• ORR (Overall Response Rate),
• Reactivation rate after 2 years,
• Molecular relapse,
• Time to negative mutation test results (in ctDNA),
• Cell line measurements.

Endpoints related to safety:
• Rate of participants presenting with Adverse Events separated by degree of intensity, category, affected organ or system.

Drugorzędowe punkty końcowe:
• PFS (Progression-Free Survival) czas przeżycia wolnego od progresji.
• OS (Overall Survival) czas przeżycia całkowitego.
• ORR (Overall Response Rate) – odsetek odpowiedzi.
• Odsetek reaktywacji po 2 latach.
• Wznowa molekularna.
• Czas do eliminacji mutacji we krwi.
• Pomiary na liniach komórkowych.

Punkty końcowe dotyczące bezpieczeństwa:
• odsetki uczestników, u których wystąpiły zdarzenia niepożądane w rozbiciu na stopień nasilenia, kategorie, dotknięty narząd lub układ.

E.5.2.1

Timepoint(s) of evaluation of this end point

Interim analyzes were planned after the enrollment of 50 patients.

Zaplanowano analizy pośrednie po włączeniu 50 pacjentów.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

Last visit of the last subject

Ostatnia wizyta ostatniego uczestnika

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

150

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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.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)

After the end of the examination, the Patient remains under standard medical care at the IMID Children's and Adolescent Oncology and Surgery Clinic until the age of 25. After the age of 25, the patient is transferred to an adult care facility.

Po zakończeniu badania pacjent pozostaje pod standardową opieką lekarską w Poradni Onkologii i Chirurgii Onkologicznej Dzieci i Młodzieży IMID do ukończenia 25 rż. Po ukończonym 25 rż pacjent zostaje przekazany do ośrodka zajmującego się opieką nad pacjentami dorosłymi.

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

2021-04-01

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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