Clinical Trials Register

Summary
EudraCT Number:	2020-001309-22
Sponsor's Protocol Code Number:	2593957
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:	2020-12-15
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

Germany - BfArM

A.2

EudraCT number

2020-001309-22

A.3

Full title of the trial

Evaluation of immunological effects of the hedgehog inhibitors on basal cell carcinoma - An open label, prospective, observational biomarker study of the DeCOG.

Bewertung der immunologischen Wirkung von Hedgehog-Inhibitoren auf das Basalzellenkarzinom - Eine offene und prospektive Biomarker-Beobachtungsstudie der Arbeitsgemeinschaft Dermatologische Onkologie.

A.3.1

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

Evaluation of immunological effects of the hedgehog inhibitors on basal cell carcinoma - An open label, prospective, observational biomarker study of the DeCOG.

A.3.2

Name or abbreviated title of the trial where available

ImmunoHedge

A.4.1

Sponsor's protocol code number

2593957

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	IQVIA Commercial GmbH & Co. OHG
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	Sun Pharmaceuticals Germany 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	IQVIA Commercial GmbH & Co. OHG
B.5.2	Functional name of contact point	Sponsor
B.5.3	Address:
B.5.3.1	Street Address	Unterschweinstiege 2-14
B.5.3.2	Town/ city	Frankfurt am Main
B.5.3.3	Post code	60549
B.5.3.4	Country	Germany
B.5.4	Telephone number	+496966040
B.5.5	Fax number	+496996759066
B.5.6	E-mail	mathias.uhlig@iqvia.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	Odomzo
D.2.1.1.2	Name of the Marketing Authorisation holder	Sun Pharmaceutical Industries Europe B.V.
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.3.1	Product name	Sonidegib
D.3.4	Pharmaceutical form	Capsule, hard
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	Sonidegib
D.3.9.1	CAS number	956697-53-3
D.3.9.3	Other descriptive name	SONIDEGIB
D.3.9.4	EV Substance Code	SUB123432
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	200
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	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	Erivedge
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
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.3.1	Product name	Vismodegib
D.3.4	Pharmaceutical form	Capsule, hard
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	Vismodegib
D.3.9.1	CAS number	879085-55-9
D.3.9.3	Other descriptive name	VISMODEGIB
D.3.9.4	EV Substance Code	SUB32354
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Basal cell carcinoma

Basalzellkarzinom

E.1.1.1

Medical condition in easily understood language

White skin cancer

Weißer Hautkrebs

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10064679
E.1.2	Term	Basal cell carcinoma of skin in situ
E.1.2	System Organ Class	100000004864

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 objective:
Immunologic assessment of advanced Basal Cell Carcinoma before and during hedgehog inhibitor therapy as measured by single cell ribonucleicacid-sequencing (scRNA-seq) and T-cell receptor sequencing (scTCR-seq) in 10X Genomics technology, bulk transcriptomics by EDGEseq, and multiplexed immunofluoresence.

Primäres Ziel:
Immunologische Beurteilung des fortgeschrittenen Basalzellkarzinoms vor und während der Therapie mit Hedgehog-Inhibitoren, gemessen mittels Einzelzell-Ribonukleinsäure-Sequenzierung (RNA-seq) und T-Zell-Rezeptor-Sequenzierung (TCR-seq) in der 10X Genomics-Technologie sowie Bulk-Transcriptomics mittels EDGEseq und Multiplex-Immunfluoreszenz.

E.2.2

Secondary objectives of the trial

Secondary objective:
Efficacy of hedgehog inhibition.

Sekundäres Ziel:
Wirksamkeit der Hedgehog-Inhibition.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histologically confirmed diagnosis of advanced BCC (surgery or radiotherapy not possible, contra¬indicated or refused by patient).
2. Decision to perform medical treatment with a hedgehog inhibitor with either sonidegib or vismodegib as SoC by an interdisciplinary tumor board. Patients who already received a previous hedgehog inhibitor treatment which was discontinued at least 90 days before start of actual hedgehog inhibitor treatment may also be enrolled.
3. Possibility and consent to perform one biopsy of at least 0.5ccm (pea-sized) before initiation of treatment and an additional biopsy 14 days after start of treatment, respectively.
4. Age ≥ 18 years.
5. Ability to understand and sign a written informed consent.
6. Expected survival of at least 6 months.
7. ECOG performance status 0, 1 or 2.
8. Rest period of at least 2 weeks to prior major surgery, radiotherapy or any previous systemic or local treatment.
9. Adequate laboratory parameters including blood count, renal and liver function parameters.
- hemoglobin > 9g/L, thrombocytes > 75.000/µL, leukocytes > 2000/µL,
- creatinine < 2x upper limit of normal (ULN) or glomerular filtration rate > 30mL/min,
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5x ULN, bilirubin < 3x ULN.
10. Adequate contraception according to Pregnancy Prevention Program of the respective hedgehog inhibitor.
11. No concomitant use of other approved or investigational antitumor agents.
12. No other serious illnesses, in particular hematological neoplasia, which might impact the outcome of the patient or the uptake of the drug significantly.
13. Consent to participation in the the prospective skin cancer patients’ registry of Arbeitsgemeinschaft Dermatologische Onkologie (ADOREG) is mandatory for study participation.

1. Histologisch bestätigte Diagnose eines fortgeschrittenen BCC (Operation oder Strahlentherapie nicht möglich, kontraindiziert oder vom Patienten abgelehnt).
2. Entscheidung einer interdisziplinären Tumorkonferenz, eine medizinische Behandlung mit einem Hedgehog-Inhibitor - entweder Sonidegib oder Vismodegib - als Standardbehandlung durchzuführen. Patienten, die zuvor bereits eine Behandlung mit einem Hedgehog-Inhibitor erhalten hatten, die mindestens 90 Tage vor der geplanten Hedgehog-Inhibitor-Therapie beendet wurde, können ebenfalls in die Studie eingebracht werden.
3. Möglichkeit und entsprechende Einwilligung zu einer Biopsie von mindestens 0,5 ccm (erbsengroß) vor Therapiestart sowie 14 Tage nach Therapiestart.
4. Alter ≥ 18 Jahre
5. Fähigkeit, die schriftliche Patienteninformation und Einwilligungserklärung zu verstehen und zu unterzeichnen.
6. Erwartetes Überleben von mindestens 6 Monaten.
7. ECOG-Status von 0, 1 oder 2.
8. Intervall von mindestens 2 Wochen nach einer vorangegangenen größeren Operation, einer Strahlentherapie oder einer anderen vorherigen systemischen oder lokalen Behandlung.
9. Adäquate Laborparameter, einschließlich Blutbild, Nieren- und Leberfunktionsparameter:
- Hämoglobin > 9 g/l, Thrombozyten > 75.000/µl, Leukozyten > 2.000/µl,
- Kreatinin < 2x obere Normgrenze (upper limit of normal, ULN) oder glomeruläre Filtrationsrate > 30 ml/min,
- Alanin-Aminotransferase (ALT) und Aspartat-Aminotransferase (AST) < 5x ULN, Bilirubin < 3x ULN.
10. Adäquate Empfängnisverhütung gemäß des Schwangerschaftsverhütungsprogramms des entsprechenden Hedgehog-Inhibitors.
11. Keine gleichzeitige Anwendung anderer zugelassener oder experimenteller antitumoraler Wirkstoffe.
12. Keine andere schwerwiegende Erkrankung, insbesondere keine hämatologische Neoplasie, welche das Patientenergebnis oder die Aufnahme des Medikaments signifikant beeinflussen könnte.
13. Einwilligung zur Aufnahme in das prospektive klinische Register für Hautkrebspatienten der Arbeitsgemeinschaft Dermatologische Onkologie (ADOREG) ist für die Studienteilnahme verpflichtend.

E.4

Principal exclusion criteria

1. Current use of immunosuppressive medication, EXCEPT for the following:
- Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection),
- Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent,
- Steroids as premedication for hypersensitivity reactions (e.g., Computed tomography [CT] scan premedication).
2. Active infection requiring systemic therapy.
3. Known history of testing positive for Human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
4. Pregnancy or lactation period.
5. Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.
6. Known alcohol or drug abuse.
7. Legal incapacity or limited legal capacity.

1. Derzeitige Anwendung von Immunsuppressiva, außer den nachfolgenden:
- Intranasale, inhalative, topische Steroide oder lokale Steroidinjektion (z. B. intraartikuläre Injektion),
- systemische Kortikosteroide in physiologischen Dosen ≤ 10 mg/Tag Prednison oder gleichwertig,
- Steroide als Prämedikation für Überempfindlichkeitsreaktionen (z. B. Prämedikation vor Computertomographie[CT]-Aufnahmen).
2. Aktive Infektion, die eine systemische Therapie erfordert.
3. Bekannter positiver Test auf das Human-Immundefizienz-Virus (HIV) oder bekanntes erworbenes Immundefekt-Syndrom (AIDS) in der Anamnese.
4. Schwangerschaft oder Stillzeit.
5. Medizinische oder psychologische Bedingungen, die verhindern könnten, dass der Patient die Studie beendet oder die Patienteninformation und Einwilligungserklärung unterzeichnet.
6. Bekannter Alkohol- oder Drogenmissbrauch.
7. Rechtsunfähigkeit oder beschränkte Rechtsfähigkeit.

E.5 End points

E.5.1

Primary end point(s)

Quantification as well as differentiation and activation status of tumor-infiltrating T cells.

Quantifizierung sowie Bestimmung der Differenzierung und des Aktivierungsstatus infiltrierender T-Zellen.

E.5.1.1

Timepoint(s) of evaluation of this end point

Timepoints of evaluation: day 14, 6 and 12 weeks after start of hedgehog inhibitor therapy.

Zeitpunkte der Bewertung: Tag 14 sowie nach 6 bzw. 12 Wochen nach Start der Hedgehog-Inhibitor-Therapie.

E.5.2

Secondary end point(s)

Tumor response at month three after start of hedgehog-inhibitor therapy (end of study).

Ermittlung der Tumoransprechrate nach drei Monaten Hedgehog-Inhibitor-Therapie (Studienende).

E.5.2.1

Timepoint(s) of evaluation of this end point

Month three after start of hedgehog-inhibitor therapy (end of study).

Monat 3 nach Start der Hedgehog-Inhibitor-Therapie (Studienende).

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

Yes

E.6.13.1

Other scope of the trial description

Biomarker analysis.

Biomarker-Analyse.

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

Yes

E.8.1.7.1

Other trial design description

Prospektive Biomarker-Beobachtungsstudie

Prospective, observational biomarker study

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

Last visit of last subject.

Letzte Visite des letzten Patienten.

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

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.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)

Patients will continue to be treated after end of study with hedgehog inhibitors as standard of Care if medically indicated.

Patienten werden nach dem Ende der Studie auch weiterhin mit Hedgehog-Inhibitoren behandelt (falls medizinisch indiziert).

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

2021-03-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-12

P. End of Trial
P.	End of Trial Status	Completed

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