Clinical Trials Register

Summary
EudraCT Number:	2017-002611-34
Sponsor's Protocol Code Number:	54767414MMY2036
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-01-17
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

France - ANSM

A.2

EudraCT number

2017-002611-34

A.3

Full title of the trial

A Randomized, Open-label, Multicenter, Multiphase Study of JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, Administered in Combination with Daratumumab, Compared with Daratumumab Alone in Subjects with Relapsed or Refractory Multiple Myeloma.

A.3.1

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

A multiphase study assessing the anti-tumor activity and safety of JNJ-63723283 (an Anti-PD-1 monoclonal antibody) administered in combination with daratumumab, compared with daratumumab alone in subjects with relapsed or refractory Multiple Myeloma.

A.4.1

Sponsor's protocol code number

54767414MMY2036

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	Janssen-Cilag International N.V.
B.1.3.4	Country	Belgium
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	Janssen Research & Development, LLC
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	Janssen-Cilag International N.V.
B.5.2	Functional name of contact point	Clinical Registry group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31715242166
B.5.5	Fax number	+31 715242110
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	JNJ-63723283
D.3.4	Pharmaceutical form	Concentrate 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	Not Assigned
D.3.9.1	CAS number	Not Assigned
D.3.9.2	Current sponsor code	JNJ-63723283
D.3.9.3	Other descriptive name	JNJ-63723283-AAA
D.3.9.4	EV Substance Code	SUB183887
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	10
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.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	DARZALEX
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International N.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/13/1153
D.3 Description of the IMP
D.3.1	Product name	Daratumumab
D.3.2	Product code	HuMax-CD38
D.3.4	Pharmaceutical form	Concentrate 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	DARATUMUMAB
D.3.9.1	CAS number	945721-28-8
D.3.9.2	Current sponsor code	JNJ-54767414 (Daratumumab)
D.3.9.3	Other descriptive name	HUMAX-CD38
D.3.9.4	EV Substance Code	SUB175772
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	20
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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	human monoclonal antibody

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

Relapsed or Refractory Multiple Myeloma (MM).

E.1.1.1

Medical condition in easily understood language

Blood cancer formed by malignant plasma cells that develops in the bone marrow and is non-responsive to therapy or relapses following treatment.

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10028228
E.1.2	Term	Multiple myeloma
E.1.2	System Organ Class	100000004864

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

Primary Objective:
Part1 (Safety Run-in): To assess the safety of the combination of JNJ-63723283 and daratumumab.
Part 2 (Phase 2): To compare the overall response rate (ORR) in subjects treated with JNJ-63723283 in combination with daratumumab versus daratumumab alone.
Part 3 (Phase 3): To compare progression-free survival (PFS) in subjects treated with JNJ-63723283 in combination with daratumumab versus daratumumab alone.

E.2.2

Secondary objectives of the trial

Phase 2 & Phase 3:
-To assess the safety of of the combination of JNJ 63723283 and daratumumab.
-To compare the complete response (CR)/better rate & very good partial response (VGPR)/better rate; duration of response and time to response; the minimal residual disease (MRD)-negative rate of JNJ-63723283 in combination with daratumumab versus daratumumab alone.
-To evaluate the pharmacokinetic & immunogenicity profile of JNJ-63723283 in combination with daratumumab & the profile of daratumumab alone or in combination with JNJ-63723283.
-To compare PFS & OS of JNJ-63723283 in combination with daratumumab versus daratumumab alone.
-To evaluate the ORR & OS.
-To assess the disease-related symptoms,functioning,quality of life (QOL) and health status by using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) & European Quality of Life 5 Dimensions Questionnaire (EQ-5D-5L).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Each potential subject must satisfy all of the following criteria to be enrolled in the study.
1. At least 18 years of age.
2. Have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) in any order during the course of treatment for multiple myeloma or have disease that is refractory to both a PI and an IMiD. (For subjects who have received more than 1 type of PI, their disease must be refractory to the most recent one.Similarly, for those who have received more than 1 type of IMiD, their disease must be refractory to the most recent one).
3. Evidence of a response to at least 1 prior treatment regimen.
4. Documented measurable disease for multiple myeloma at screening as defined by the criteria below:
-IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
-IgA, IgM, IgD, or IgE multiple myeloma: serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or
-Light chain multiple myeloma without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
5. Have relapsed or refractory disease at time of enrollment as defined below:
•Relapsed disease is defined as an initial response to previous treatment, followed by progressive disease (PD) by International Myeloma Working Group (IMWG) criteria >60 days after cessation of treatment.
•Refractory disease is defined as <25% reduction in M-protein or PD by IMWG criteria during previous treatment or ≤60 days after cessation of treatment.
6. Eastern Cooperative Oncology Group Performance Status (ECOG)performance status score of 0, 1, or 2.
7. Adequate organ function (bone marrow, liver, renal)
8. Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
9. Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.

E.4

Principal exclusion criteria

Any potential subject who meets any of the following criteria will be excluded from the study:
1. Received any of Anti-CD38 antibody, including daratumumab or Anti-PD-1 and anti-PD-L1 antibodies in the past.
2. Clinically significant cardiac or pulmonary disease.
3. Prior diagnosis of autoimmune disease with the exception of subjects:
- With autoimmune thyroid disease or type 1 diabetes that is well controlled on a stable medication regimen
- With vitiligo, alopecia, or resolved childhood asthma/atopy
- With psoriasis not requiring systemic therapy
- With transient autoimmune manifestations of an acute infectious disease that resolved upon treatment of the infectious agent.
3. Unresolved Grade 2 or higher toxicity effects from previous treatment with immunotherapy not recovered to Grade ≤1 or baseline
4. Received any of the following prescribed medications or therapies within the specified period:
- Antimyeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, prior to first administration of study drug. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment prior to first administration of study drug.
- An allogenic stem cell transplant (SCT) at any time; or autologous SCT within 12 weeks prior to first administration of study drug.
- Other investigational agent (including investigational vaccines), participation in another clinical study with therapeutic intent, or used an invasive investigational medical device within 28 days or 5 pharmacokinetic half-lives of the investigational agent (whichever is longer) prior to first administration of study drug.
- Systemic radiotherapy within 14 days prior to first administration of study drug.
5. Plans to undergo a stem cell transplant prior to progression of disease on this study.
6. History of malignancy (other than multiple myeloma) within 2 years prior to first administration of study drug
7. Known or suspected of not being able to comply with the study protocol.

E.5 End points

E.5.1

Primary end point(s)

1. Incidence of adverse events (including dose-limiting toxicities (DLTs) (Part 1 [Safety Run-in] Group)
2. Overall response rate (ORR; as defined by IMWG response criteria (Part 2 [Phase 2] group)
3. Progression-free survival (PFS) (Part 3 [Phase 3] group)

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Evaluation after 6 subjects have received 1 treatment cycle (28 days).
2. Evaluation after 80 subjects have received at least 4 treatment cycles.
3. Primary Analysis after 138 PFS events.

E.5.2

Secondary end point(s)

Phase2 & Phase 3 Groups:
1. Incidence of adverse events, including immune-related AEs and infusion-related reactions
2. Complete response (CR) or better rate (as defined by the IMWG response criteria)
3. Very good partial response (VGPR) or better rate (as defined by the IMWG response criteria)
4. Duration of response
5. Time to response
6. Progression-free survival (PFS)
7. Incidence of anti-JNJ-63723283 antibodies
8. Incidence of anti-daratumumab antibodies
9. Overall survival (OS)
10. MRD-negative rate
11. Serum JNJ-63723283 Concentration (Cmin, Cmax)
12. Serum daratumumab pharmacokinetic Concentration (Cmin, Cmax)
Part 3 (Phase 3) Group:
13. Overall response rate (ORR)
14. Change from baseline in disease-related symptom scales, functioning scales, and Global Health Status (GHS) scale of the EORTC QLQ-C30, and the utility scale and visual analog scale (VAS) of the EQ-5D-5L

E.5.2.1

Timepoint(s) of evaluation of this end point

1. After 50 subjects have been enrolled and have been treated for at least 8 weeks or discontinued the study treatment
2 to 8. Part 2: At 12 months; Part 3: At 138 events
9. Part 2: At 12 months; Part 3: After 205 deaths have been observed
10. At the time of disease progression & at every 6 months in subjects with maintained CR & stringent complete response (sCR)
11. Cycle (C)1 Day (D)1, C1 D2, D1 of C 2,3,5, 7,12,16 & 24; every 12 cycles thereafter until end of treatment (EOT)
12. C1 D1, C1 D2, D1 of C 2,3,5, 7,12&24; every 12 cycles thereafter until EOT
13. Part 2: At 12 months; Part 3: At 138 events
14. D1 of every 3rd cycle (Cycles 3,6,9,12) until progressive disease (PD)

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

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity and Biomarker Analyses.

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)

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Multicenter study

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

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

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

Belgium

France

Germany

Greece

Israel

Russian Federation

Spain

Turkey

United States

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

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:

154

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

232

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

386

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)

The sponsor will provide standard of care treatment.

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

2018-03-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-03-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-11-19

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