ICH GCP - EU Clinical trials Registry - 2022-001786-12 (IT)

Summary
EudraCT Number:	2022-001786-12
Sponsor's Protocol Code Number:	CDX0159-08
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2023-01-23
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

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	CELLDEX THERAPEUTICS, INC
B.1.3.4	Country	United States
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	Celldex Therapeutics, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Celldex Therapeutics, Inc.
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	53 Frontage Road, Suite 220
B.5.3.2	Town/ city	Hampton
B.5.3.3	Post code	NJ 08827
B.5.3.4	Country	United States
B.5.6	E-mail	clinicaltrials@celldex.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	barzolvolimab
D.3.2	Product code	[CDX-0159]
D.3.4	Pharmaceutical form	Concentrate for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	2438203-51-9
D.3.9.2	Current sponsor code	CDX-0159
D.3.9.4	EV Substance Code	SUB219179
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Concentrate for solution for injection/infusion
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Eosinophilic esophagitis (EoE)

Esofagite eosinofila

E.1.1.1

Medical condition in easily understood language

Eosinophilic esophagitis (EoE) is an inflammatory disease of the food
pipe that involves eosinophils, a type of white blood cell.

L'esofagite eosinofila (EoE) è una malattia infiammatoria del cibo
tubo che coinvolge gli eosinofili, un tipo di globuli bianchi.

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	10064220
E.1.2	Term	Eosinophilic esophagitis
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

To evaluate efficacy of barzolvolimab, compared to placebo, in reducing esophageal intraepithelial infiltration of mast cells as assessed by peak esophageal intraepithelial mast cell (PMC) count in EoE patients.

È stata valutata l'efficacia di barzolvolimab, rispetto al placebo, nella riduzione dell'infiltrazione intraepiteliale esofagea dei mastociti valutata mediante la conta di picco dei mastociti intraepiteliali esofagei (PMC) nei pazienti EoE.

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy of barzolvolimab, compared to placebo, inreducing symptoms of dysphagia as assessed by dysphagia symptom questionnaire (DSQ) in EoE patients
• To evaluate efficacy of barzolvolimab, compared to placebo, in reducing esophageal intraepithelial infiltration of eosinophils as assessed by peak esophageal intraepithelial eosinophil (PEC) count in EoE patients
• To evaluate the safety profile of barzolvolimab in EoE patients

• Valutare l'efficacia di barzolvolimab, rispetto al placebo, nel ridurre i sintomi della disfagia valutati dal sintomo della disfagia questionario (DSQ) nei pazienti EoE
• Valutare l'efficacia di barzolvolimab, rispetto al placebo, nel ridurre l'infiltrazione intraepiteliale esofagea degli eosinofili valutata mediante la conta di picco degli eosinofili intraepiteliali esofagei (PEC) nei pazienti EoE
• Valutare il profilo di sicurezza di barzolvolimab nei pazienti EoE

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

Other types of substudies
Specify title, date and version of each substudy with relative objectives: Dense Pharmacokinetic and Biomarker Sampling:
In addition to the PK sampling for all patients as per the protocol scheldue of assessments, dense sampling will occur at select sites during the Active Treatment Phase. This sampling will provide supplementary PK and PD data to better characterize the absorption of barzolvolimab and the kinetics of tryptase suppression in the study population. Dense sampling will be conducted at select centers in approximately 12 patients who consent.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Campionamento denso di farmacocinetica e biomarcatori:
Oltre al campionamento farmacocinetico per tutti i pazienti come da protocollo scheldue delle valutazioni, il campionamento denso avverrà in siti selezionati durante la fase di trattamento attivo. Questo campionamento fornirà supplementare Dati PK e PD per caratterizzare meglio l'assorbimento di barzolvolimab e la cinetica della soppressione della triptasi nella popolazione in studio. Denso il campionamento sarà condotto presso centri selezionati in circa 12 pazienti che acconsentono.

E.3

Principal inclusion criteria

1. Read, understood, and provided written informed consent, after the nature of the study has been fully explained.
2. Male or female, = 18 years of age at the time of signing the informed consent.
3. Documented diagnosis of EoE by endoscopy.
4. Esophageal intraepithelial eosinophilic infiltration, with peak esophageal intraepithelial eosinophil count (PEC) of = 15 per high power field (hpf) from at least 2 of 3 levels (proximal, mid, and distal) of the
esophagus at the Screening/Baseline esophagogastroduodenoscopy (EGD) at the Screening Visit.
5. Must be symptomatic, defined as:
a. History (by patient report) of an average of at least 2 days per week with dysphagia with intake of solid foods during 1 month prior to the Screening Visit and
b. At least 4 days with dysphagia (answer of "Yes" to DSQ Question #2) within the last 2 weeks immediately prior to randomization.
6. Must have been on a stable diet which includes solid foods for at least 2 months prior to the Screening Visit and throughout the study.
Note: Stable diet is defined as no initiation or elimination of single or multiple food groups or reintroduction of previously eliminated food groups.
7. Have had inadequate response to or is inappropriate for and/or intolerant to a standard-of-care treatment for EoE (e.g., PPI, swallowed topical corticosteroids, or dietary elimination) based on the
investigator's clinical judgment.

1. Letto, compreso e fornito consenso informato scritto, dopo che la natura dello studio è stata completamente spiegata.
2. Maschio o femmina, = 18 anni di età al momento della firma del consenso informato.
3. Diagnosi documentata di EoE mediante endoscopia.
4. Infiltrazione eosinofila intraepiteliale esofagea, con picco di conta eosinofila intraepiteliale esofagea (PEC) = 15 per campo ad alta potenza (hpf) da almeno 2 dei 3 livelli (prossimale, medio e distale) del
esofago allo Screening/Esofagogastroduodenoscopia (EGD) al basale alla Visita di Screening.
5. Deve essere sintomatico, definito come:
un. Anamnesi (secondo il referto del paziente) di una media di almeno 2 giorni alla settimana con disfagia con assunzione di cibi solidi durante 1 mese prima della visita di screening e
b. Almeno 4 giorni con disfagia (risposta "Sì" alla domanda DSQ n. 2) nelle ultime 2 settimane immediatamente prima della randomizzazione.
6. Deve aver seguito una dieta stabile che includa cibi solidi per almeno 2 mesi prima della visita di screening e durante lo studio.
Nota: la dieta stabile è definita come assenza di inizio o eliminazione di uno o più gruppi di alimenti o reintroduzione di gruppi di alimenti precedentemente eliminati.
7. Avere avuto una risposta inadeguata o inappropriata e/o intollerante a un trattamento standard di cura per EoE (ad es. PPI, corticosteroidi topici ingeriti o eliminazione attraverso la dieta) in base al giudizio clinico dello sperimentatore.

E.4

Principal exclusion criteria

1. Diagnosis of hypereosinophilic syndrome or Churg-Strauss syndrome or eosinophilic granulomatosis with polyangiitis).
2. History of a clinicopathologic diagnosis of eosinophilic gastritis or eosinophilic duodenitis.
3. Known active Helicobacter pylori infection.
4. History of coagulation disorders or esophageal varices.
5. History of achalasia, Crohn's disease, ulcerative colitis or celiac disease.
6. Esophageal dilation within 3 months prior to the Screening Visit.
7. Avoiding solid foods or using feeding tube.
8. Non-biologic systemic (oral or injectable) agents within 2 months prior to the Screening Visit.
9. Biologic therapy within 3 months or 5 half-lives, whichever is longer, prior to the Screening Visit.
Note: Biologic agents include but are not limited to interleukin (IL)-4 receptor inhibitor (dupilumab), IL-5 inhibitors (e.g., mepolizumab,
benralizumab), IL-13 inhibitors (e.g., tralokinumab, lebrikizumab), anti-IgE (e.g., omalizumab), IFN-¿ inhibitors, or other approved or investigational biologics.
10. Diagnosis of idiopathic anaphylaxis or other severe allergic reactions that in the opinion of the investigator, could increase the patient's risk
for systemic hypersensitivity reactions; or any known contraindications or hypersensitivity to any component of study treatments, drugs of similar chemical classes (i.e., to murine, chimeric or human antibodies) or antihistamines.
11. Women who are pregnant or nursing. All female patients with reproductive potential must have a negative pregnancy test prior to starting study treatment.

1. Diagnosi di sindrome ipereosinofila o sindrome di Churg-Strauss o granulomatosi eosinofila con poliangioite).
2. Storia di una diagnosi clinicopatologica di gastrite eosinofila o duodenite eosinofila.
3. Infezione attiva nota da Helicobacter pylori.
4. Anamnesi di disturbi della coagulazione o varici esofagee.
5. Storia di acalasia, morbo di Crohn, colite ulcerosa o celiachia.
6. Dilatazione esofagea entro 3 mesi prima della visita di screening.
7. Evitare cibi solidi o utilizzare un tubo di alimentazione.
8. Agenti sistemici non biologici (orali o iniettabili) nei 2 mesi precedenti la visita di screening.
9. Terapia biologica entro 3 mesi o 5 emivite, qualunque sia la più lunga, prima della visita di screening.
Nota: gli agenti biologici includono, ma non sono limitati a, inibitore del recettore dell'interleuchina (IL)-4 (dupilumab), inibitori dell'IL-5 (ad esempio, mepolizumab,
benralizumab), inibitori dell'IL-13 (ad es. tralokinumab, lebrikizumab), anti-IgE (ad es. omalizumab), inibitori dell'IFN-¿ o altri farmaci biologici approvati o sperimentali.
10. Diagnosi di anafilassi idiopatica o altre gravi reazioni allergiche che, a parere dello sperimentatore, potrebbero aumentare il rischio del paziente
per reazioni di ipersensibilità sistemica; o qualsiasi controindicazione nota o ipersensibilità a qualsiasi componente dei trattamenti in studio, farmaci di classi chimiche simili (ad esempio, ad anticorpi murini, chimerici o umani) o antistaminici.
11. Donne incinte o che allattano. Tutte le pazienti di sesso femminile con potenziale riproduttivo devono avere un test di gravidanza negativo prima di iniziare il trattamento in studio.

E.5 End points

E.5.1

Primary end point(s)

Absolute change from baseline to Week 12 in the PMC/high power field
(hpf)

Variazione assoluta dal basale alla settimana 12 nel campo PMC/high power

E.5.1.1

Timepoint(s) of evaluation of this end point

Screening (baseline), week 12 TEAEs: continuously until end of study visit.

Screening (basale), settimana 12 TEAR: ininterrottamente fino alla fine della visita dello studio.

E.5.2

Secondary end point(s)

• Absolute change from baseline to Week 12 in PEC/hpf
• Absolute change from baseline to Week 12 in the sum of PMC/hpf and PEC/hpf mong patients with baseline PMC = 12/hpf
• Absolute change from baseline to Week 12 in PEC/hpf
• Percent (%) change from baseline to week 12 in PMC7hpf
• Incidence of TEAEs

• Variazione assoluta dal basale alla settimana 12 in PEC/hpf
• Variazione assoluta dal basale alla settimana 12 nella somma di PMC/hpf e PEC/hpf tra i pazienti con PMC al basale = 12/hpf
• Variazione assoluta dal basale alla settimana 12 in PEC/hpf
• Variazione percentuale (%) dal basale alla settimana 12 in PMC7hpf
• Incidenza di TEAE

E.5.2.1

Timepoint(s) of evaluation of this end point

Screening (baseline), week 12 TEAEs: continuously until end of study visit.

Screening (basale), settimana 12 TEAR: ininterrottamente fino alla fine della visita dello studio.

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

Yes

E.6.7

Pharmacodynamic

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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)

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

Information not present in EudraCT

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

Australia

Canada

United States

Poland

Spain

Germany

Italy

United Kingdom

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

E.8.9.2

In all countries concerned by the trial days

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