Clinical Trials Register

Summary
EudraCT Number:	2021-000545-40
Sponsor's Protocol Code Number:	FELZ01
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-23
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

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A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2021-000545-40

A.3

Full title of the trial

Safety, Tolerability and Efficacy of Monoclonal CD38 Antibody Felzartamab in Late Antibody-Mediated Renal Allograft Rejection – A Phase 2 Pilot Trial

Sicherheit, Verträglichkeit und Effektivität des monoklonalen CD38 Antikörpers Felzartamab bei später Antikörper-vermittelter Nierentransplantatabstoßung – Eine Phase 2 Pilotstudie

A.3.1

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

Safety, Tolerability and Efficacy of the Therapeutic Antibody Felzartamab in Rejection Late After Kidney Transplantation

Sicherheit, Verträglichkeit und Wirksamkeit des therapeutischen Antikörpers Felzartamab bei Abstoßung spät nach Nierentransplantation

A.3.2

Name or abbreviated title of the trial where available

Felzartamab in late ABMR

Felzartamab bei später ABMR

A.4.1

Sponsor's protocol code number

FELZ01

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	Medical University of Vienna
B.1.3.4	Country	Austria
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	MorphoSys AG
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	Medical University of Vienna
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Währinger Gürtel 18-20
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1090
B.5.3.4	Country	Austria
B.5.4	Telephone number	+43140400 43630
B.5.5	Fax number	+43140400 39302
B.5.6	E-mail	georg.boehmig@meduniwien.ac.at

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	Felzartamab
D.3.4	Pharmaceutical form	Lyophilisate for 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	Felzartamab
D.3.9.1	CAS number	2197112-39-1
D.3.9.2	Current sponsor code	MOR202
D.3.9.4	EV Substance Code	SUB216362
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	65
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	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	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Late active or chronic active antibody-mediated rejection

E.1.1.1

Medical condition in easily understood language

Immunological rejection of a kidney transplant late after transplantation

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The main objective of the trial is to evaluate the safety and tolerability of CD38 monoclonal antibody felzartamab in a prospective cohort of kidney transplant recipients diagnosed with late active or chronic active ABMR.

E.2.2

Secondary objectives of the trial

The trial will evaluate preliminary efficacy of targeting CD38 in late active ABMR (secondary endpoints), and can be expected to provide a valuable basis for the potential design of a pivotal trial powered for the detection of clinical outcome differences.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Voluntary written informed consent
Age >18 years (maximum: 70 years)
Functioning living or deceased donor allograft after ≥180 days post-transplantation
eGFR ≥20 ml/min/1.73 m2 (CKD-EPI formula)
HLA class I and/or II antigen-specific antibodies (preformed and/or de novo DSA).
Active or chronic/active ABMR (±C4d in PTC) according to the Banff 2019 classification
Molecular ABMR score (MMDx) ≥0.2

E.4

Principal exclusion criteria

Patients actively participating in another clinical trial
Age ≤18 years
Female subject is pregnant or lactating or not on adequate contraceptive therapy
ABO-incompatible transplant
Index biopsy results:
T-cell-mediated rejection classified Banff grade ≥I
De novo or recurrent severe thrombotic microangiopathy
Polyoma virus nephropathy
De novo or recurrent glomerulonephritis
Acute rejection treatment ≤3 month before screening
Previous treatment with other CD38 monoclonal antibodies (e.g. daratumumab)
Previous treatment with other immunomodulatory monoclonal/polyclonal antibodies (e.g. CD20 Ab rituximab, IL-6/IL-6R Ab) ≤3 months before study treatment
Total bilirubin >2×the upper limit of normal [ULN], alanine transaminase and aspartate aminotransferase >2·5×ULN
Haemoglobin <8 g/dL
Thrombocytopenia: Platelets <100 G/L
Leukopenia: Leukocytes <3 G/L
Neutropenia: Neutrophils < 1.5 G/L
Hypogammaglobulinemia: Serum IgG <400 mg/dL
Active viral, bacterial or fungal infection precluding intensified immunosuppression
Active malignant disease precluding intensified immunosuppressive therapy
Latent or active tuberculosis (positive QuantiFERON-TB-Gold test)
Administration of a live vaccine within 6 weeks of screening
History of alcohol or illicit substance abuse
Serious medical or psychiatric illness likely to interfere with participation in the study

E.5 End points

E.5.1

Primary end point(s)

Safety and tolerability of felzartamab in renal allograft recipients with ABMR on baseline immunosuppression

E.5.1.1

Timepoint(s) of evaluation of this end point

Over the study period of 52 weeks

E.5.2

Secondary end point(s)

- DSA/immunoglobulin levels
Mean fluorescence intensity (MFI) of immunodominant DSA
Changes in levels of the immunodominant DSA calculated from dilution experiments
Number of detected DSA
Total Ig (IgG, IgA, IgM) and IgG subclasses (IgG1, IgG2, IgG3, IgG4)
Course of vaccination titers

- Effect on leukocyte subsets in peripheral blood
Circulating PC, NK cells, T and B cell subpopulations, expression of CD38 using non- crossreactive CD38 Ab clone HIT2

- Results of follow-up protocol biopsies
Morphological results:
ABMR category (active vs. chronic active ABMR; C4d+ vs. C4d- ABMR)
Extent of glomerular/pertibulular capillary microcirculation inflammation (g+ptc score)
Transplant glomerulopathy (cg) and interstitial fibrosis/tubular atrophy scores
Intragraft complement activation
Patterns of intragraft cellular infiltrates (NK cells, PC, T cells, B cells)
Gene expression analysis (Molecular Microscope® Diagnostic System, MMDx)
Molecular classifiers/scores related to ABMR and T cell-mediated rejection
Molecular classifiers/scores related to rejection in general
Molecular classifiers/scores related to acute and chronic renal injury
Archetypal analysis of rejection-related categories
Pathogenesis-based transcripts (PBT) scores (cytotoxic T cell infiltration, γ-interferon effects, NK cell burden, epithelial cell damage

- Effect on immunologic biomarkers
CXCL9 and CXCL10 levels in blood and urine (Luminex-based detection)
BAFF levels in blood (ELISA/Luminex)

- Effect on measures of overall immunosuppression
Torque Teno virus (TTV) levels in plasma (quantitative PCR)

-Effect on clinical outcome parameters and surrogate endpoints:
eGFR slope
iBox clinical prediction score
Protein excretion (protein/creatinine ratio)
Death-censored/overall graft and patient survival

E.5.2.1

Timepoint(s) of evaluation of this end point

DSA/immunoglobulin levels: week 0, 12, 24, and 52

Effect on leukocyte subsets in peripheral blood : week 0, 1, 4, 8, 12, 24, and 52

Follow-up protocol biopsies: week 24 and 52

Immunologic biomarkers: week 0, 12, 24, and 52

Measures of overall immunosuppression: week 0, 12, 24, and 52

Clinical outcome parameters and surrogate endpoints:
-eGFR slope: over a period of 52 weeks (4-weekly measurements)
-iBox clinical prediction score: at, 24 and 52 weeks
-Protein excretion (protein/creatinine ratio): over 52 weeks (4-weekly measurements)
-Death-censored/overall graft and patient survival: over 52 weeks

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

Yes

E.8.4

The trial involves multiple sites in the 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

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

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 months

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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 the completion, data base lock and unblinding of the randomized controlled phase of the trial, the study can optionally be extended to a 5-year observational period (Option A) and/or, in the event of sufficient safety and potential efficacy of felzartamab, to a subsequent 1-year uncontrolled open-label treatment phase (Option B: 16 mg/kg Felzartamab IV per infusion; Infusions are planned at day 0, after 1, 2, 3, 4, 8, 12, 16, and 20 weeks; observation until week 52).

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

2021-08-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-05-11

P. End of Trial
P.	End of Trial Status	Ongoing

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