Clinical Trials Register

Summary
EudraCT Number:	2019-001554-25
Sponsor's Protocol Code Number:	371
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-10-29
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

2019-001554-25

A.3

Full title of the trial

Adalimumab dose optimization in rheumatoid arthritis using therapeutic
drug monitoring (ADDORA): multi-center single blinded randomized controlled
trail

A.3.1

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

Adalimumab dose optimization in rheumatoid arthritis using drug
concentration in blood (ADDORA): multi-center single blinded randomized
controlled trail

A.3.2

Name or abbreviated title of the trial where available

ADalimumab Dose Optimization in Rheumatoid Arthritis using (ADDORA)

A.4.1

Sponsor's protocol code number

371

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	Reade
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	ZonMw
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	Reade
B.5.2	Functional name of contact point	Principal Investigator
B.5.3	Address:
B.5.3.1	Street Address	Dr. Jan van Breemenstraat 2
B.5.3.2	Town/ city	Amsterdam
B.5.3.3	Post code	1056AB
B.5.3.4	Country	Netherlands
B.5.6	E-mail	g.wolbink@reade.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Humira, Hulio, Amgevita, Hyrimoz, Idacio, Imraldi
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbvie, Mylan, Amgen, Sandoz, Fresenius Kabi, Biogen
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	Adalimumab
D.3.2	Product code	D2E7
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.4	EV Substance Code	SUB20016
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	40
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)	Yes
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

Rheumatoid arthritis

reumatoide artritis

E.1.1.1

Medical condition in easily understood language

Rheumatoid arthritis

reuma

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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 is to evaluate whether adalimumab dose reduction
using adalimumab serum measurements (TDM strategy) will minimize
medical costs, compared to disease activity guided dose reduction in
rheumatoid arthritis (RA) patients.

E.2.2

Secondary objectives of the trial

The secondary objectives are to investigate the percentage of patients
reaching minimal disease activity (DAS28-CRP<2.9) in both study arms;
to study the difference in cumulative incidence of flares between the
study arms; to evaluate the algorithm used to prolong the dose-interval
based on adalimumab concentration; to study the difference in
cumulative incidence of flares between discontinuation of treatment
after 52 weeks and continuation of treatment aiming a low adalimumab
serum concentration

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-rheumatoid arthritis patient, according to ACR 1987 or ACR/EULAR 2010 criteria
- adalimumab < 16 weeks at registered dose of 40mg every other week
-who has agreed to participate (written informed consent);
-age 16 years or older.

E.4

Principal exclusion criteria

-Life expectancy shorter than follow-up period of the study;
-Other disease that might flare if adalimumab is tapered like psoriasis,
inflammatory bowel disease.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint:
- Direct medical costs associated with adalimumab dose reduction using
TDM versus using disease activity scores over 52 weeks.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 52

E.5.2

Secondary end point(s)

Secondary endpoint
- Difference in mean time weighted DAS28-CRP at 16, 28, 52 and 80
weeks.
- Direct medical costs (medication, visits, cost TDM testing) at the
separate time points (after 28 and 80 weeks).
- Indirect medical costs at the separate time points at 28, 52 and 80
weeks of treatment.
- Percentage of patients with DAS28-CRP<2.9 at 52 and 80 weeks.
- Number of flares and dose-interval shortenings at 52 and 80 weeks.
- Agreement between algorithm predicted and measured adalimumab
concentrations

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 16, 28,40, 52, 80

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Optimizing the dose and reducing over exposure

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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

Yes

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

Yes

E.8.2.3.1

Comparator description

Dose reduction strategy using disease activity vs. dose reduction strategy using drug concentration

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

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

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:

132

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

221

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)

After the end of the study patients can decide with their treating
rheumatologist to continue the reduced dose or to start full dose.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Reade
G.4.3.4	Network Country	Netherlands
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	Sint Maartenskliniek
G.4.3.4	Network Country	Netherlands
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	Noordwest ziekenhuisgroep
G.4.3.4	Network Country	Netherlands
G.4 Investigator Network to be involved in the Trial: 4
G.4.1	Name of Organisation	Maxima Medisch Centrum
G.4 Investigator Network to be involved in the Trial: 5
G.4.1	Name of Organisation	Reumazorg Zuidwest Nederland
G.4 Investigator Network to be involved in the Trial: 6
G.4.1	Name of Organisation	Amsterdam UMC
G.4.3.4	Network Country	Netherlands

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-10-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-10-04

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

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