Clinical Trials Register

Summary
EudraCT Number:	2022-001484-27
Sponsor's Protocol Code Number:	NL67672.091.18
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-10-29
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2022-001484-27

A.3

Full title of the trial

B cell Activation in Sjögren's Syndrome, Cutaneous Lupus Erythematodus and Systemic Sclerosis Tissues
Analysis 2

B cel activatie in Syndroom van Sjögren, Cutane Lupus Erythematodus en Systemische Sclerose Weefsel
Analyse 2

A.3.1

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

Basta 2

A.3.2

Name or abbreviated title of the trial where available

Basta 2

A.4.1

Sponsor's protocol code number

NL67672.091.18

A.5.4

Other Identifiers

Name:

PaNaMa

Number:

107802

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	radboudumc
B.1.3.4	Country	Netherlands
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	Radboudumc
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	Health Holland Match PPS
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	ReumaNederland
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	GSK
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	Galapagos
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Radboudumc
B.5.2	Functional name of contact point	department of rheumatology
B.5.3	Address:
B.5.3.1	Street Address	G. Grooteplein Z-10
B.5.3.2	Town/ city	Nijmegen
B.5.3.3	Post code	6525 GA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031(0)243614580
B.5.6	E-mail	rogier.thurlings@radboudumc.nl

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	[89Zr]Zr-Df-crefmirlimab berdoxam
D.3.2	Product code	IND 127861
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	Solution for infusion (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	[89Zr]Zr-Df-crefmirlimab berdoxam
D.3.9.3	Other descriptive name	Minibody against CD8 conjugated to desferrioxamine labeled with zirconium Zr 89
D.3.9.4	EV Substance Code	SUB218013
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/ml megabecquerel(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4.625
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	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

Systemic Sclerosis
Sjögren's Syndrome
Cutaneous Lupus Erythematodus

Systemische Sclerose
Syndroom van Sjögren
Cutane Lupus Erythematodus

E.1.1.1

Medical condition in easily understood language

Scleroderma
Sjögren's Syndrome
CLE

Sclerodermie
Syndroom van Sjögren
CLE

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

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

Objective: Investigate patients with CLE, SSj and SSc to:
1. Comparatively analyze the B and T cell repertoire in locoregional lymph node versus blood and involved skin (CLE, SSc) and salivary gland (SSj) for shared clonal expansions, somatic hypermutation, preferential gene usage and ontogenetic relations.
2. analyze lineage commitment and expression of activation and regulatory factors of activated and expanded T cell clones in the locoregional lymph node.
3. Analyze the subset origin of expanded B cell clones by comparative analysis of FACS sorted B cells from peripheral blood.
4. Compare [18F]FLT and [89Zr] Df-IAB22M2C anti-CD8 PET imaging as a tool to select involved lymph nodes for biopsy.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

General inclusion criteria are age > 50 years for patients undergoing a [89Zr] anti-CD8 PET scan because of the necessary radioactive dose for this scan.

Inclusion criteria for SSj patients are: diagnosis of primary SSj according to the European American consensus group criteria (15) and presence of anti-nuclear (ANA), anti-SSA and/or anti-SSB antibodies.

Inclusion criteria for CLE patients are: diagnosis of subacute cutaneous lupus erythematosus (SCLE) or SLE with cutaneous lupus according to the Düsseldorf classification criteria (22). Presence of anti-nuclear (ANA), anti-SSA and/or anti-SSB antibodies. Active skin disease as assessed by the treating physician.

Inclusion criteria for the SSc patients are: diagnosis of early diffuse cutaneous SSc, according to the VEDOSS criteria defined as having a diffuse skin involvement, presence of anti-nuclear antibodies (ANA), a disease duration (from first non-Raynaud symptom) of < 3 years and progressive disease as defined by an increase in mean Rodnan skin score (mRSS) > 10 points or > 25% in the past year. Patients will be selected with skin involvement of the legs, which allows the analysis of an inguinal lymph node as locoregional lymph node.

E.4

Principal exclusion criteria

Exclusion criteria for SSj, CLE and SSc patients are presence of active concurrent inflammatory or infectious condition, current or previous use of biologic treatment, previous other systemic autoimmune disease diagnosis or positive serology for hepatitis C or Human Immunodeficiëncy Virus.

SSj, CLE and SSc patients will be asked for separate consent for collection of a lymph node tissue biopsy. Analysis of lymph node biopsies in patients with allow the direct comparison of autoreactive B and T cell expansions, controlling for tissue specific regulatory mechanisms.

E.5 End points

E.5.1

Primary end point(s)

The difference between CLE, SSj and SSc in differentiation, activation and regulation of expanded B and T cell clones, shared between locoregional lymph node versus involved skin and salivary gland

E.5.1.1

Timepoint(s) of evaluation of this end point

LVLS

E.5.2

Secondary end point(s)

Not applicable

E.5.2.1

Timepoint(s) of evaluation of this end point

LVLS

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

E.6.4

Safety

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

Yes

E.6.13.1

Other scope of the trial description

An exploratory analysis in three transversal patient cohorts involving two study visits for clinical assessment, blood withdrawal, [18F]FLT and [89Zr] anti-CD8 PET imaging (1:1) and 1) for SSj patients a salivary gland biopsy and optionally a lymph node biopsy, 2) for SSc and CLE patients a skin biopsy of involved an of uninvolved skin and optionally a lymph node biopsy.

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

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

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

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

F.3.3.1

Women of childbearing potential not using contraception