Clinical Trials Register

Summary
EudraCT Number:	2008-007185-33
Sponsor's Protocol Code Number:	3242K1-2000-WW
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-09-10
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2008-007185-33

A.3

Full title of the trial

A Seamless, Phase 1/2, Multiple Ascending Dose, Proof of Concept Study of ATN-103
Administered to Subjects With Active Rheumatoid Arthritis on a Background of
Methotrexate

A.4.1

Sponsor's protocol code number

3242K1-2000-WW

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Wyeth Pharmaceuticals Inc. Acting through its division Wyeth Research, a Pfizer Company
B.1.3.4	Country	United States
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	ATN-103
D.3.2	Product code	ATN-103
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	ATN-103
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	50
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	ATN-103 is a humanized, trivalent, bi-specific tumor necrosis factor (TNF)-inhibiting fusion protein.

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	Powder for solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Rheumatoid arthritis

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.0
E.1.2	Level	LLT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis

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 evaluate the safety and clinical efficacy of multiple ascending
doses (MAD) of ATN-103 administered SC to subjects with active RA compared with placebo.

E.2.2

Secondary objectives of the trial

To assess the tolerability, PK, pharmacodynamic (PD), and the
optimal treatment frequency regimen for ATN-103 (administered every 4 weeks versus every 8 weeks).

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Intensive Pharmacokinetics Sampling:
A full ATN-103 PK profile will be obtained in a subgroup of up to 50 subjects; this is described in the main clinical trial protocol.

E.3

Principal inclusion criteria

1. Male and female subjects between the ages of ≥ 18 years and ≤ 80 years at the time of signing the ICF.
2. Meets the American College of Rheumatology (ACR, formerly American Rheumatism
Association) 1987 revised criteria for classification of RA at least 24 weeks prior to
screening.
3. ACR functional class I to III.
4. Active RA at the time of screening and at baseline consisting of ≥ 6 swollen and
≥ 6 tender joints (28-joint count).
5. The hs-CRP ≥ 8 mg/L (.8 mg/dL) at screening (as determined by blood specimen sent to the Central Lab). The screening hs-CRP may be repeated once during the screening period.
6. Must be receiving MTX for at least 12 weeks, with a stable dose and route of MTX
(7.5 - 25 mg weekly) for at least 6 weeks prior to baseline and continuing on that dose for the duration of the study.
7. The report of a chest radiograph performed within 12 weeks of the screening visit (chest radiograph must be performed during the screening if no prior chest radiograph report is available) documenting the absence of any evidence of malignancy, infection, or abnormalities suggestive of tuberculosis must be obtained and available in the subject’s study file prior to baseline.
8. All women of childbearing potential (WOCBP) must have a negative serum pregnancy test result at screening and a negative urine pregnancy test result at baseline.
 WOCBP are defined as women who are biologically capable of becoming pregnant,
including women who are using contraceptives or whose sexual partners are either
sterile or using contraceptives.
 Women of non-childbearing potential (WONCBP) are defined as either
postmenopausal (history of amenorrhea for ≥ 52 weeks) or who are surgically sterile, such as after hysterectomy, bilateral oophorectomy, or tubal ligation (procedure performed ≥ 52 weeks before screening). This information must be documented in the subject’s source documents.
 WONCBP do not require a serum and urine pregnancy test.
9. WOCBP who have sexual intercourse with a non-surgically sterilized male must agree and commit to the use of the following highly effective methods of contraception for duration of the study (defined as the time of the signing of the ICF through the conclusion of subject participation). Contraceptive methods considered acceptable for use in this study include:
• Established use of oral, injected or implanted hormonal methods of contraception.
• Double barrier contraception: Use of occlusive diaphragm (cap or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
• Intrauterine device or system
10. All men (unless surgically sterile, as defined below) who have sexual intercourse with a WOCBP must agree and commit to use a highly effective methods of contraception for the duration of the study (defined as the time of the signing of the ICF through the conclusion of subject participation). Highly effective methods of contraception include properly used spermicidal condom.
• To be considered surgically sterilized, a male partner must have had a vasectomy at least 24 weeks before study day 1
11. Willingness and ability to participate in all aspects of the study, including SC
administration of investigational product (by unblinded study personnel), completion of subject assessments, attending scheduled clinic visits, and compliance with all protocol requirements as evidenced by written informed consent.

E.4

Principal exclusion criteria

1. Pregnant women or nursing mothers.
2. Presence of active infections, fungal infections (minor nail and skin infections will be allowed, ie, Tinea Pedis), or open cutaneous ulcers, any underlying diseases that could predispose subjects to infections, or history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks of baseline visit.
3. Significant concurrent, medical conditions at the time of screening or baseline visit
including, but not limited to:
 Any major illness/condition or evidence of an unstable clinical condition, such as,
renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, immunologic
(eg, Felty’s syndrome, human immunodeficiency virus [HIV], infections,
neurological, cerebral psychiatric disease, or evidence of demyelinating disease
which, in the investigator’s judgment, will substantially increase the risk associated with the subject developing an adverse event (AE) or serious adverse event (SAE)
during the study, or preclude the evaluation of the subject’s response.
 A history or current evidence of latent or active tuberculosis infection, evidence of prior or currently active tuberculosis by chest radiography, recent close contact with an individual with active tuberculosis. Subjects who have a positive Mantoux (PPD) tuberculin skin test during screening or within 12 weeks prior to randomization. Documentation of the dose and product used as well as the official test reading must be obtained and available in the subject’s study file.
A positive Mantoux tuberculin skin test is defined as ≥ 5 mm of induration (or as defined by country specific or local standards) at 48-72 hours without consideration of prior Bacillus Calmette-Guérin (BCG) vaccination. However, if the results of the Mantoux tuberculin skin test are thought to represent a false positive eg, < 10 mm, induration possibly due to prior BCG vaccination then performing Interferon Gamma Release Assay (the following are acceptable assays, Quantiferon or T-spot) test is appropriate and must be negative or the patient is excluded. Documentation of prior BCG vaccination and timing (if known), the IGRA product used, the reason for using it and the test result, should be in the subject’s study file.
 A history or suspicion (received antibiotics) of a joint prosthesis infection if
prosthesis not removed or replaced.
 Any rheumatologic disease other than RA, including but not limited to Lyme disease, primary Sjögren’s syndrome, psoriatic arthritis, spondyloarthropathy, systemic lupus erythematosus, systemic vasculitis, polymyositis, infectious arthritis, reactive arthritis (Reiter’s syndrome), or scleroderma.
 Current or history of cancer or lymphoproliferative disease within previous 5 years (resected cutaneous basal cell or squamous cell carcinoma are exempt from time limit) that has been treated with no evidence of recurrence.
 Class III or IV congestive heart failure as defined by the New York Heart Association
 Acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) and
any history of significant cerebrovascular disease within 24 weeks of screening.
 Have a transplanted organ.
 Documented history of any drug-induced liver injury, liver cirrhosis, or fibrosis at any time before baseline visit.
4. Abnormality in hematology or biochemistry profiles at screening:
 Positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis C antibody (HepCAb) with confirmation by recombinant immuno blot assay (RIBA).
 Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels
≥ 2 times the upper limit of normal (ULN).
 Hemoglobin levels ≤ 85 g/L (8.5 g/dL).
 Platelet count ≤ 125 x 10 power 9/L (125,000 cells/mm³) or ≥ 1,000 x 10 power 9/L (1,000,000 cells/ mm³).
 White blood cell count ≤ 3.5 x 10 power 9/L (3,500 cells/ mm³).
 Serum creatinine levels ≥ 177 μmol/L (2 mg/dL).
Screening laboratory tests if considered by the investigator to be transient and inconsistent with the subject’s clinical condition may be repeated once during the screening period for confirmation.
5. Any prior use of B cell-depleting therapy.
6. All drugs which have efficacy in RA (excluding MTX) should be discontinued for
sufficient time that there is minimal systemic exposure or residual therapeutic activity.
A comprehensive but not exhaustive list of drugs and the duration they should be discontinued for prior to entering the study is provided in the clinical trial protocol exclusion criteria section.
7. Known or suspected allergy to ATN-103, any type of TNFi, human immunoglobulin
proteins or other compounds related to these classes of medication.
8. Current or history of psychiatric disease, alcohol or drug abuse that, in the opinion of the investigator, would interfere with the ability to comply with the protocol or give informed consent.

E.5 End points

E.5.1

Primary end point(s)

ACR20 response at Week 16.

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

Yes

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)

Yes

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.8.3

The trial involves single site in the Member State concerned

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

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

Information not present in EudraCT

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

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

Last subject last visit

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.1.3

Elderly (>=65 years)

Yes

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

240

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)

Subjects who complete clinical trial 3242K1-2000-WW will be offered participation in an open-label extension study (under a separate protocol) where they will receive ATN-103 regardless of treatment arm cohort assignment in clinical trial 3242K1-2000-WW.

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

2009-10-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-02-01

P. End of Trial
P.	End of Trial Status	Completed

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