Clinical Trials Register

Summary
EudraCT Number:	2021-004328-13
Sponsor's Protocol Code Number:	CD8-PET
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-10-27
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

Germany - PEI

A.2

EudraCT number

2021-004328-13

A.3

Full title of the trial

Early detection of side effects in patients with metastatic melanoma receiving immune checkpoint inhibitor therapy by investigation of the CD8+ immune infiltrate using [89Zr]Zr-Df-IAB22M2C-PET

A.3.1

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

The purpose of this study is to determine to which extent CD8+ T-cell distribution evaluated noninvasively by PET imaging with the tracer [89Zr]Zr-Df-IAB22M2C provides a diagnostic gain in the early detection of adverse immune-mediated side effects induced by ICT

A.4.1

Sponsor's protocol code number

CD8-PET

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	University Hospital Tübingen
B.1.3.4	Country	Germany
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	University Hospital Tübingen
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	University Hospital Tübingen
B.5.2	Functional name of contact point	Zentrum für klinische Studien
B.5.3	Address:
B.5.3.1	Street Address	Frondsbergstr. 23
B.5.3.2	Town/ city	Tübingen
B.5.3.3	Post code	72070
B.5.3.4	Country	Germany
B.5.4	Telephone number	0049070712985273
B.5.5	Fax number	0049070712925080
B.5.6	E-mail	zks-pm@med.uni-tuebingen.de

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-IAB22M2C-PET
D.3.2	Product code	[89Zr]Zr
D.3.4	Pharmaceutical form	Injection/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	INN-[89Zr]Zr-Df-IAB22M2C
D.3.9.3	Other descriptive name	[89Zr]Zr-Df-IAB22M2C
D.3.9.4	EV Substance Code	SUB124979
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	37
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

Adult male or female patients scheduled for ICT with metastasized or irresectable melanoma

E.1.1.1

Medical condition in easily understood language

melanoma patients

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

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	10025650
E.1.2	Term	Malignant melanoma
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	10025670
E.1.2	Term	Malignant melanoma stage III
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	10027480
E.1.2	Term	Metastatic malignant melanoma
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

E.2 Objective of the trial

E.2.1

Main objective of the trial

• Feasibility of the early detection of immune-mediated ICT side effects by semiquantitative assessment of CD8+ lymphocyte infiltration using noninvasive [89Zr]Zr-Df-IAB22M2C PET imaging

E.2.2

Secondary objectives of the trial

• To assess the prediction of immune-mediated ICT side effects by using noninvasive [89Zr]Zr-Df-IAB22M2C PET imaging for semiquantitative assessment of CD8+ lymphocyte infiltration.
• To assess the correlation of the CD8+ lymphocyte infiltration in the tumors, metastasis and lymphoid organs by [89Zr]Zr-Df-IAB22M2C PET with treatment response to ICT according to clinical standard of care [18F]-FDG PET/CT until 6 months after start of ICT
• Assessment of potential side effects of [89Zr]-Df-IAB22M2C up to 24h p.i.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

All patients must meet all the following criteria:
•Male or female patients ≥18 years of age at the time of signing
the informed consent
 Patients with metastasized or irresectable melanoma stage
III/IV
 Eastern Cooperative Oncology Group Performance (ECOG)
Status ≤ 2
 Patients scheduled for ICT by tumor board decision
 Understand and voluntarily sign an informed consent
document prior to any study related assessments/
procedures.
 Able to adhere to the study visit schedule and other protocol
requirements
 Consent to practice double-barrier contraception until end of
the study (28 days after last [89Zr]Zr-Df-IAB22M2C injection)
Females of childbearing potential (FCBP1) and male patients
with female partner of childbearing potential1 is willing to use
highly effective contraceptive methods at least 28 days
before starting study drug, while participating in the study
(including dose interruptions), and for at least 28 days after
end of study treatment after the last dose.must agree
Recommendations (CTFG Recommendations related to
contraception and pregnancy testing in clinical trials. Version
1.1, 2020) highly effective contraceptive methods are:
a) combined hormonal contraception associated with
inhibition of ovulation (oral, intravaginal, transdermal)
b) progestogen-only hormonal contraception associated
with inhibition of ovulation (oral, injectable, implantable)
c) intrauterine device (IUD)
d) intrauterine hormone - releasing system (IUS)
e) bilateral tubal occlusion
f) vasectomized partner (2)
g) sexual abstinence (3)
1A female is considered of childbearing potential (FCBP), i.e. fertile,
following menarche and until becoming post-menopausal unless
permanently sterile. Permanent sterilisation methods include
hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A
postmenopausal state is defined as no menses for 12 months without an
alternative medical cause. A high follicle stimulating hormone (FSH) level
in the postmenopausal range may be used to confirm a post-menopausal
state in women not using hormonal contraception or hormonal
replacement therapy. However, in the absence of 12 months of
amenorrhea, a single FSH measurement is insufficient. For the purpose
of this document, a man is considered fertile after puberty unless
permanently sterile by bilateral orchidectomy.
2Vasectomised partner is a highly effective birth control method provided
that partner is the sole sexual partner of the WOCBP trial participant and
that the vasectomised partner has received medical assessment of the
surgical success.
3In the context of the CTFG guidance () sexual abstinence is considered
a highly effective method only if defined as refraining from heterosexual
intercourse during the entire period of risk associated with the study
treatments. The reliability of sexual abstinence needs to be evaluated in
relation to the duration of the clinical trial and the preferred and usual
lifestyle of the subject.

E.4

Principal exclusion criteria

Patients will be excluded if one or more of the following criteria are
met:
 Known hypersensitivity to [89Zr]Zr-Df-IAB22M2C or its
components or to any drug with similar chemical structure or
to any excipient present in the pharmaceutical form of the
investigational medicinal product.
 Clinical signs of active infection (>Grade 2 according to
CTCAE version 5.0).
 Major surgery within 4 weeks of starting study treatment.
Patients must have recovered from any effects of major
surgery.
 Heart failure NYHA III/IV.
 Patients not able to declare meaningful informed consent on
their own.
 Women during pregnancy and lactation; female patients of
childbearing potential or male patients with female partners of
childbearing potential not willing to practice effective
contraception by using a double-barrier method from Day 0
until 28 days post-dose.
 Male patients planning to donate sperm while participating in
the study and for at least 28 days after end of study treatment.
 Participation in other clinical trials or observation period of
competing trials.

E.5 End points

E.5.1

Primary end point(s)

Number of patients who are affected by grade 3/4 (CTCAE) ICT related side effects with detectable differences in [89Zr]Zr-Df-IAB22M2C PET-imaging before and after the first cycle of ICT

E.5.1.1

Timepoint(s) of evaluation of this end point

Number of patients who are affected by grade 3/4 (CTCAE) ICT related side effects with detectable differences in [89Zr]Zr-Df-IAB22M2C PET-imaging before and after the first cycle of ICT (3 weeks)

E.5.2

Secondary end point(s)

• Absolute uptake of [89Zr]Zr-Df-IAB22M2C as assessed by PET imaging before the first cycle of ICT in the organs predisposed for immune related side effects and lymphatic tissue in the patients with autoimmune side effects grade 3/4 (CTCAE) induced by ICT compared to patients without grade 3/4 (CTCAE) autoimmune side effects of ICT.
• % uptake difference of [89Zr]Zr-Df-IAB22M2C before and after the first cycle of ICT in the organs predisposed for immune related side effects and the lymphatic tissue in the patients with autoimmune grade 3/4 (CTCAE) side effects induced by ICT compared to patients without autoimmune side effects of ICT.
• Number of patients with detectable differences in [89Zr]Zr-Df-IAB22M2C uptake before and after the first cycle of ICT in the tumors, metastasis or the lymphatic tissue, who are showing a clinical response to ICT.
• Absolute uptake of [89Zr]Zr-Df-IAB22M2C before the first cycle of ICT in the tumors, metastasis and lymphatic tissue in the patients who are showing a clinical response to ICT compared to non-responders.
• % uptake difference of [89Zr]Zr-Df-IAB22M2C uptake before and after the first cycle of ICT in the tumors and metastasis as well as in the lymphatic organs in patients who are showing a clinical response to ICT

E.5.2.1

Timepoint(s) of evaluation of this end point

before and after the first cycle of ICT (3 weeks)

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

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

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

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

The end of the trial is defined as the last visit of the last subject.

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)

Following completion of this study, all treatments and interventions will be at the investigators’ discretion according to standard-of-care clinical practice and patients’ needs.

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

2022-03-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-02-14

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

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