Clinical Trials Register

Summary
EudraCT Number:	2015-005282-22
Sponsor's Protocol Code Number:	42847922MDD2001
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:	2018-01-12
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

2015-005282-22

A.3

Full title of the trial

A Multicenter, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled, Adaptive Dose-Finding Study to Evaluate the Efficacy and Safety of JNJ-42847922 as Adjunctive Therapy to Antidepressants in Adult Subjects With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy

A.3.1

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

A study to evaluate the safety and efficacy of JNJ 42847922 along with your antidepressant in adult patients with Major Depressive Disorder whose antidepressant medication has not satisfactorily treated their symptoms

A.4.1

Sponsor's protocol code number

42847922MDD2001

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 NV
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 NV
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	2333CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031 0 71524 2166
B.5.5	Fax number	0031 0 71524 2110
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-42847922 10 mg
D.3.2	Product code	JNJ-42847922
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	1452539-75-1
D.3.9.2	Current sponsor code	JNJ-42847922-AAA
D.3.9.4	EV Substance Code	SUB32046
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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	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	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	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-42847922 20 mg
D.3.2	Product code	JNJ-42847922
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	1452539-75-1
D.3.9.2	Current sponsor code	JNJ-42847922-AAA
D.3.9.4	EV Substance Code	SUB32046
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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	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	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	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Major Depressive Disorder (MDD)

E.1.1.1

Medical condition in easily understood language

Depression

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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	10025453
E.1.2	Term	Major depressive disorder NOS
E.1.2	System Organ Class	100000004873

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1. To assess the dose-response relationship of up to 3 doses of JNJ 42847922 (20 and 40 mg, with 10 mg potentially added at the interim analysis) compared to placebo as adjunctive therapy to an antidepressant drug in improving depressive symptoms in subjects with MDD who have had an inadequate response to current antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).
2. To assess the safety and tolerability of JNJ 42847922 compared to placebo as adjunctive therapy to an antidepressant in subjects with MDD.

E.2.2

Secondary objectives of the trial

To assess the efficacy of JNJ-42847922 compared to placebo as adjunctive therapy to an antidepressant in improving:
1. Depressive symptoms in subjects with MDD with significant insomnia symptoms (baseline Insomnia Severity Index [ISI] score ≥15) versus those without significant insomnia symptoms (baseline ISI score <15).
2. Response and remission of depressive symptoms, Anxiety symptoms, Response of anxiety symptoms, Clinical severity, Global functioning (work/school, social and family life).
3. Depressive symptoms in the subpopulation of subjects with MDD with anxious distress

4. To evaluate the effect of JNJ-42847922 exposure on the HPA axis in subjects with MDD
5. To assess the exposure of JNJ-42847922 and metabolites M12 and M16 in subjects with MDD
6 To capture patient-reported assessment of JNJ 42847922 compared to placebo as adjunctive therapy to an antidepressant

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female, aged 18 to 64 years (inclusive). Note: Subjects should be at least 18 years of age or older as per the legal age of consent in the jurisdiction in which the study is taking place.
2. Meet DSM-5 diagnostic criteria for MDD, without psychotic features (DSM-5 296.22, 296.23, 296.32, or 296.33), based upon clinical assessment and confirmed by the SCID-CT. In addition their major depressive episode must be deemed “valid” using the SSQ interview administered by remote, independent raters. The length of the current depressive episode must be ≤1 year.
3. Have had an inadequate response to at least 1 but no more than 2 antidepressants (see the inclusion criterion below), administered at an adequate dose and duration in the current episode of depression, as measured by the MGH-ATRQ. An inadequate response is defined as <50% reduction in depressive symptom severity, as assessed by the MGH-ATRQ. An adequate trial is defined as an antidepressant treatment for at least 4 weeks at at least the minimum therapeutic dose specified in the MGH-ATRQ, for any particular antidepressant. The inadequate response must include the subject’s current antidepressant treatment.
4.Is receiving monotherapy treatment for depressive symptoms with one of the following SSRI/SNRI antidepressants, in any formulation: citalopram, duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, desvenlafaxine, vilazodone, or vortioxetine at at least the minimum therapeutic dose for at least 4 weeks, and for no greater than 6 months, at screening. Modification of an effective preexisting therapy should not be made for the explicit purpose of entering a subject into the study.
5. Have a MADRS total score ≥25 (performed by independent, centralized remote raters) at screening and must not demonstrate a clinically significant improvement (ie, an improvement of >20% on their MADRS total score) from the screening to baseline visit.

E.4

Principal exclusion criteria

1. Has a history of, or current signs and symptoms of, severe renal insufficiency (creatinine clearance <30 mL/min); moderate to severe hepatic insufficiency (Child-Pugh Score 7-9), significant or unstable cardiovascular, respiratory, gastrointestinal, neurologic, hematologic, rheumatologic, immunologic or endocrine disorders (including uncontrolled hypo- or hyperthyroidism or diabetes, or insulin-dependent diabetes mellitus). Subjects with non-insulin dependent diabetes mellitus who are well-controlled (hemoglobin A1C [HbA1C] ≤7% and fasting glucose <126 mg/dL at screening) may be eligible to participate if otherwise medically healthy, and if on a stable regimen of glucose-lowering medications for at least 2 months prior to screening.
2. Has current signs/symptoms of hypothyroidism or hyperthyroidism (Subjects with known hypothyroidism who have been on stable treatment for at least 3 months prior to screening are required to have thyroid stimulating hormone [TSH] and free thyroxine [FT4] obtained. Any subject with an elevated TSH should also have FT4 measured. In any case where the TSH value is out of range, but FT4 is normal, the findings should be discussed directly with the medical monitor before the subject is enrolled. If the FT4 value is out of range, the subject is not eligible. Subjects taking thyroid supplementation for antidepressant purposes are not allowed in the study).
3. Has signs and symptoms of Cushing’s Disease, Addison’s Disease, primary amenorrhea, or other evidence of significant medical disorders of the HPA axis.
4. Has a current or recent history of serious suicidal ideation within the past 6 months, corresponding to a positive response on item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) for ideation on the C-SSRS, or a history of suicidal behavior within the past year, as validated by the C SSRS at screening or Day 1. Subjects with a prior suicide attempt of any sort, or prior serious suicidal ideation/plan within the past 6 months, should be carefully screened for current suicidal ideation and only subjects with non-serious items (1-3 of the suicidal ideation section of the C-SSRS) may be included at the discretion of the investigator.
5. Has a history of lack of response to 3 or more adequate antidepressant treatments.

E.5 End points

E.5.1

Primary end point(s)

1. Change from baseline to the end of Week 6 in the MADRS total score.
2. Safety assessments, including adverse events, laboratory values, electrocardiogram (ECG), vital signs, physical exam, the Columbia Suicide Severity Rating Scale (C-SSRS), the Arizona Sexual Experiences Scale (ASEX), and the Physician Withdrawal Checklist (PWC).

E.5.1.1

Timepoint(s) of evaluation of this end point

N/A

E.5.2

Secondary end point(s)

1. Correlation between baseline ISI score as a continuous variable and change from baseline to the end of Week 6 in the MADRS total score.
2. Change from baseline to the end of Week 6 in the MADRS total score in subjects with baseline ISI score ≥15 versus subjects with baseline ISI score <15.
3. Shift in ISI score category from baseline to the end of Week 6.
4. Proportion of responders on depressive symptoms scale, defined as a ≥50% improvement in MADRS total score from baseline to the end of Week 6.
5. Proportion of subjects with remission of depressive symptoms, defined as a MADRS total score ≤8, ≤10, or ≤12 at the end of Week 6.
6. Change from baseline to the end of Week 6 on the 14-item Hamilton Anxiety Rating scale (HAM-A) total score.
7. Proportion of responders on anxiety symptoms scale, defined as a ≥50% improvement in the HAM-A total score from baseline to the end of Week 6.
8. Change from baseline to the end of Week 6 in the Clinical Global Impression-Severity (CGI-S) score.
9. Change from baseline to the end of Week 6 in the Sheehan Disability Scale (SDS).
10. Change from baseline to the end of Week 6 in the MADRS total score in subjects with MDD with anxious distress versus subjects with MDD without anxious distress.
11. Change from baseline to Weeks 2, 4, and 6 in salivary cortisol levels, as measured upon awakening.
12. Observed plasma concentrations of JNJ 42847922 and metabolites and estimated exposure parameters for JNJ-42847922 from population based pharmacokinetic (PK) modeling.
13. Change from baseline to the end of Week 6 in:
- Depressive symptoms using the Patient Health Questionnaire 9-item (PHQ-9)
-Anhedonia using the Snaith-Hamilton Pleasure Scale (SHAPS)
-Sleep disturbance using the Patient Reported Outcome Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form
- Fatigue using the PROMIS Fatigue Short Form
-Severity of depression using the Patient Global Impression-Severity (PGI-S)
-Health related quality of life and utility using the European Quality of Life (EuroQol) Group, 5 Dimension, 5-Level (EQ-5D-5L) questionnaire
- Work productivity and limitations using the Work Limitations Questionnaire (WLQ) Short Form.

E.5.2.1

Timepoint(s) of evaluation of this end point

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

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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

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

Bulgaria

Finland

Germany

Japan

Russian Federation

Ukraine

United States

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

The study is considered completed with the final study visit for the last subject participating in the study.

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

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:

280

F.1.3

Elderly (>=65 years)

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

280

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)

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

2018-03-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-04-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-01-19

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