Clinical Trials Register

Summary
EudraCT Number:	2019-003567-21
Sponsor's Protocol Code Number:	CHDR1912
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-09-30
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

Netherlands - Competent Authority

A.2

EudraCT number

2019-003567-21

A.3

Full title of the trial

A randomized, evaluator-blind, vehicle controlled, parallel group study to explore the effects of the anti-inflammatory drug prednisolone in a TLR4 and TLR7 challenge model in healthy volunteers

A.3.1

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

Anti-inflammatory drugs in a TRL4 and TLR7 topical challenge model

A.4.1

Sponsor's protocol code number

CHDR1912

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	Centre for Human Drug Research
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	Centre for Human Drug Research
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Centre for Human Drug Research
B.5.2	Functional name of contact point	Principal Investigator
B.5.3	Address:
B.5.3.1	Street Address	Zernikedreef 8
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CL
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31715246400
B.5.5	Fax number	+31715246499
B.5.6	E-mail	clintrials@chdr.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	Yes
D.2.1.1.1	Trade name	Aldara 5%
D.2.1.1.2	Name of the Marketing Authorisation holder	Meda AB
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Aldara
D.3.4	Pharmaceutical form	Ointment
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IMIQUIMOD
D.3.9.1	CAS number	99011-02-6
D.3.9.4	EV Substance Code	SUB12453MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	Prednisolone solution 0.5 mg/kg
D.3.4	Pharmaceutical form	Oral solution
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	Prednisolone
D.3.9.3	Other descriptive name	PREDNISOLONE SODIUM PHOSPHATE PH. EUR.
D.3.9.4	EV Substance Code	SUB179340
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	5
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	Oral solution
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

None

E.1.1.1

Medical condition in easily understood language

None

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10062249
E.1.2	Term	Skin inflammation
E.1.2	System Organ Class	100000004858

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To assess the pharmacodynamic effects of systemic prednisolone on the LPS or IMQ-induced inflammatory response
• To assess safety & tolerability of intradermal LPS and topical IMQ in combination with prednisolone

E.2.2

Secondary objectives of the trial

• To explore pharmacodynamic biomarkers determined in blister exudate compared to skin punch biopsies in LPS- or IMQ-induced inflammation.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Healthy male or female subjects (Part B males only), 18 to 45 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, blood serology and urinalysis. In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects;
2. Body mass index (BMI) between 18 and 30 kg/m2 and a maximum weight of 100 kg, inclusive;
3. Fitzpatrick skin type I-III (Caucasian);
4. Subjects and their partners of childbearing potential must use effective contraception for the duration of the study;
5. Able and willing to give written informed consent and to comply with the study restrictions.

E.4

Principal exclusion criteria

Eligible subjects must meet none of the following exclusion criteria at screening:
1. Any vaccination within the last 3 months; COVID19 vaccination is allowed up until 4 weeks prior to the first prednisolone/placebo dosing, and from 2 weeks after the last prednisolone/placebo dosing.
2. Family history of psoriasis;
3. History of pathological scar formation (keloid, hypertrophic scar);
4. Have any current and / or recurrent pathologically, clinical significant skin condition at the treatment area (i.e. atopic dermatitis); inlcuding tattoos
5. Previous use of Aldara (IMQ cream) 3 weeks prior to the baseline visit (part A only)
6. Known hypersensitivity to the (non)investigational drug, drugs of the same class, or any of their excipients;
7. Hypersensitivity for dermatological marker at screening;
8. Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrollment or planned to use during the course of the study;
9. Use of topical medication (prescription or over-the-counter [OTC]) within 30 days of study drug administration, or less than 5 half-lives (whichever is longer) in local treatment area
10. Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment;
11. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year.
12. Loss or donation of blood over 500 mL within three months prior to screening (part A and B), or donation of plasma withing 14 days of screening (part B only) .
13. Any (medical) condition that would, in the opinion of the investigator, potentially compromise the safety or compliance of the patient or may preclude the patient’s successful completion of the clinical trial.
14. Latent Diabetes Mellitus
15. Volunteers with clinically relevant infections
16. Current smoker and/or regular user of other nicotine-containing products (e.g., patches); or positive urine cotinine test at screening (part B only)
17. History of or current drug or substance abuse considered significant by the PI (or medically qualified designee), including a positive urine drug screen.
18. Subjects that test positive for a SARS-CoV-2 infection
19. Subjects with a BMI > 30 and/or cardiovascular, respiratory or immune system disorders

E.5 End points

E.5.1

Primary end point(s)

Tolerability / safety endpoints
• Adverse events (AEs)
• Vital signs
• 12-leads ECGs
• Local tolerance (erythema grading scale, numeric rating scale (NRS) pruritus and pain)
Pharmacodynamic endpoints
Non-invasive measures:
• Perfusion by Laser speckle contrast imaging (LSCI)
• Erythema by Antera 3D camera
• Erythema by clinical evaluation (erythema grading scale)
• Optical Coherence Topography (OCT) (part A only)
• 2D photography by ATBM for photo documentation only (part A only)
Invasive measures:
• Suction blister exudates, including but not limited to
o Cytokines and chemokines
o Flow cytometry (for example: neutrophils, monocytes/macrophages, CD4+ lymphocytes, CD8+ lymphocytes, CD56+ lymphocytes, CD1c dendritic cells)
• Skin punch biopsies, may include, but is not limited to
o Local biomarkers, : IL-8, IFN-α, IL-1β, IFN-ɣ, MXA, MX1, IL-6, IL-10, CCL20 and HBD-2)
o Immunohistochemistry: CD1a, HLADR, CD8+, CD4+, CD14+, CD11c, complement factors, iNOS, NETs, gasdermin, IRAK4.
o Histology (HE)
• Ex vivo blood assay
o Ex vivo cytokine release assay (imiquimod, part A only)
o Ex vivo cytokine release assay (LPS, part B only)
o Ex vivo NET assay (Part B only)

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 0 - EOS

E.5.2

Secondary end point(s)

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

E.6.6

Pharmacokinetic

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

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

Evaluator-blind

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

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)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

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)

None

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

2019-09-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-12-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-09-07

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