Clinical Trials Register

Summary
EudraCT Number:	2009-017438-32
Sponsor's Protocol Code Number:	VX09-509-101
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-04-26
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2009-017438-32

A.3

Full title of the trial

A 12-week, double-blind, randomized, parallel-group, placebo-controlled study of 4 doses of VX-509 in subjects with active rheumatoid arthritis

A.4.1

Sponsor's protocol code number

VX09-509-101

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	Vertex Pharmaceuticals Incorporated
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.3.2	Product code	VX-509
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	VX 509
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	25
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)	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	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.3.2	Product code	VX-509
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	VX 509
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	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)	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	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	Tablet
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

active rheumatoid arthritis

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
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 assess the clinical response of 4 doses of VX-509 compared to placebo in subjects
with active RA as defined by 2 endpoints: the American College of Rheumatology
defined 20% response (ACR20) and the change from baseline using Disease Activity
Score (DAS)28 improvement at Week 12

• To evaluate the safety and tolerability of VX-509 compared to placebo when
administered for 12 weeks to subjects with active RA

E.2.2

Secondary objectives of the trial

• To assess the clinical response of 4 doses of VX-509 compared to placebo in subjects with active RA using the following:
o ACR-defined 50% and 70% responses (ACR50,70) over a 12-week treatment
period
o EULAR (European League against Rheumatism) response over a 12-week
treatment period
• To assess the improvement in individual components of the ACR response of 4 doses of VX-509 compared to placebo over a 12-week treatment period
• To determine the pharmacokinetics (PK) of VX-509 when administered to subjects with active RA for 12 weeks
• To assess the phosphorylated signal transducer and activator of transcription (P-STAT) biomarker responses in blood and inflammatory protein/proteomic biomarker responses in plasma
• To assess the magnitude of improvement in quality of life (Short Form-36 [SF-361)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male subjects or female subjects who are confirmed to be of non-childbearing potential, between 18 and 75 years of age (inclusive) on the date of consent who agree on study participation and are able to read, understand, and sign and date a written ICF
2. All subjects must have been diagnosed with RA as defined by the ACR revised criteria (Appendix A), with disease duration of at least 6 months from confirmed diagnosis.
3. Subjects must have a swollen joint count of ≥ 6 out of 28 joints and tender joint count of ≥6 out of 28 joints. Joints that have had prior surgery are to be excluded from the joint count.
4. Baseline CRP level must be 1.5 times greater than the upper limit of normal at Screening.
5. Subjects must have failed at least 1 nonbiologic DMARD for any reason (please refer to Appendix B for a list of DMARDs). Subjects who have failed previous treatment with MTX must have at least a 1 -month washout period since the last dose of MTX prior to Day 1. Washout periods for other DMARDs are listed in Appendix B.
6. Subjects may have previously failed no more than 1 biologic DMARD and discontinued treatment for reasons other than inadequate response. Subjects must not have been treated with Rituximab previously. Required washout period from previous biologic DMARD is at least 60 days.
7. Female subjects must be confirmed to be of non-childbearing potential (i.e. either postmenopausal or surgically sterile) in order to be eligible for study enrollment. Female subjects will be considered postmenopausal if they have had 12 months of consecutive spontaneous amenorrhea. A follicle stimulating hormone (FSH) test will be performed locally during the Screening Visit to confirm post-menopausal status. Female subjects will be considered surgically sterile if they are post-hysterectomy, 6 months post surgical bilateral oophorectomy, or 6 months post-tubal ligation .In addition, all females must have a negative serum pregnancy test at the screening visit and also a negative urine pregnancy test at the screening visit and on Day 1 prior to study dosing. Male subjects must be willing to comply with contraception requirements as outlined in Section 12.5.5.1.
8. Subjects must agree not to participate in other interventional clinical studies for the
duration of their participation in this trial.
9. Subjects able to understand and be willing to comply with protocol requirements and instructions and likely to complete the study as planned.

E.4

Principal exclusion criteria

1. Subjects with inflammatory rheumatological disorders other than RA, where arthritis may be a prominent feature, such as systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polydermatomyositis, or Sjogren syndrome, will be excluded. Subjects with RA who have conditions associated secondarily with RA (e.g.,
osteoarthritis of affected joint[s] or sicca syndrome) may be considered for enrollment.
2. Female subjects who are considered to be of childbearing potential (i.e., are not postmenopausal or surgically sterile).
3. Male subjects with female partners that are pregnant, nursing, or planning to become pregnant during the study or within 90 days of the last dose of VX-509.
4. History or evidence of a clinically significant disorder other than RA (including but not
limited to cardiopulmonary, oncologic, renal, metabolic, hematologic or psychiatric disorders), condition or disease that, in the opinion of the investigator and medical
monitor, would pose a risk to subject safety or interfere with the study evaluation,
procedures, or completion.
5. Subjects with clinically important abnormalities in screening physical examination or in screening laboratory test results (including the presence of either hepatitis B surface
antigen, hepatitis C virus antibody, or HIV types 1 and 2 antibody).
6. Subjects with elevation in alanine aminotransferase or aspartate aminotransferase above the upper limit of normal.
7. History of hematologic disorders including neutropenia and thrombocytopenia.
8. Subjects with an acute or chronic active infection requiring systemic antimicrobial
treatment, or subjects who are at high risk of developing an infection due to a compromised immune system. Antifungals for onychomycosis or low-dose antibiotics for rosacea, that are not inhibitors or inducers of CYP3A, will be allowed.
9. Subjects who have undergone or are undergoing treatment with another investigational drug or approved treatment for investigational use within 3 months or 5 half-lives of the drug, whichever is greater.
10. Subjects who require concomitant use of any inhibitors or inducers of cytochrome P450 (CYP) 3A. Please refer to Appendix C for a partial list of such medications.
1 1. Subjects who have been treated with intra-articular injections of corticosteroids within 28 days prior to Day 1.
12. Subjects who have planned major surgery (e.g., joint replacement) or any procedures during the study.
13. Have received any live, attenuated vaccinations within 1 month prior to study drug
administration. Note: Subjects who receive study drug should not receive any type of
these vaccinations within 1 month after receiving their final dose.
14. History of drug or alcohol abuse or excessive alcohol as determined by the investigator, during the last 12 months before the screening visit.
15. History of TB infection of any kind (pulmonary or extrapulmonary, active or latent), regardless of history of anti-TB treatment. Subjects must be screened for TB by customary clinical measures (history, chest x-ray, and skin test) at Screening. Subjects with a PPD skin test with induration >5 mm and <10 mm must have: 1) a negative screening chest radiograph at Screening, 2) a history of Bacille Calmette-Guérin (BCG) vaccination, and 3) a negative serologic test for TB (such as the QuantiFERON or T-spot TB test) in order to be considered eligible for study entry. Subjects with a PPD test 10 mm or greater induration are excluded regardless of BCG vaccination history.

E.5 End points

E.5.1

Primary end point(s)

o Proportion of subjects who achieve an ACR20 response at Week 12
o Change from baseline in DAS28 at Week 12

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

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

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

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

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

The end of the study is defined as the date of final database lock

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
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	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	35
F.4.2	For a multinational trial
F.4.2.1	In the EEA	110
F.4.2.2	In the whole clinical trial	200

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

2010-07-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-06-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-07-11

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