24-week Study With Open Label Extension of VX-509, an Oral JAK3 Inhibitor, in Subjects Taking Methotrexate

Rheumatoid Arthritis Clinical Trial

Official title:

A 24-week, Double-Blind, Randomized, Parallel Group, Placebo-Controlled, Phase 2 Study of Different Doses of VX-509 in Adult Subjects With Active Rheumatoid Arthritis on Stable Methotrexate Therapy With 104-Week Open Label Extension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01590459
• Other study ID #: VX11-509-102
• Secondary ID: 2011-004419-22
• Status: Completed
• Phase: Phase 2
• First received: April 27, 2012
• Last updated: October 23, 2015
• Start date: April 2012
• Est. completion date: July 2014

Study information

• Verified date: October 2015
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesEstonia: The State Agency of MedicineHungary: National Institute for Quality and Organizational Development in Healthcare and MedicinesSlovakia: State Institute for Drug ControlCzech Republic: State Institute for Drug ControlBulgaria: Bulgarian Drug AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSerbia and Montenegro: Agency for Drugs and Medicinal DevicesUkraine: Ministry of HealthArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaRomania: National Agency for Medicines and Medical DevicesMexico: Federal Commission for Protection Against Health Risks
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the safety and efficacy of VX-509, an oral JAK3 inhibitor, for treatment of subjects with active RA who have had an inadequate response to Methotrexate.

Description:

VX-509 is an oral, selective Janus kinase 3 (JAK3) inhibitor being developed by Vertex. In autoimmune diseases, JAK3 is an essential component of the immune signaling cascade. This cascade ultimately contributes to abnormal immune response that results in chronic inflammation and, in the case of rheumatoid arthritis (RA), irreversible damage to cartilage and bones. Selective inhibition of JAK3 offers a new disease modifying approach to the treatment of RA, and a broad range of other autoimmune diseases.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 359
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Male and female subjects, between 18 and 80 years of age (inclusive)

• All subjects must have been diagnosed with RA

• Must have a swollen joint count of =6 out of 66 joints and tender joint count of =6 out of 68 joints

• Baseline CRP level must be above the upper limit of normal

• All subjects must have been receiving stable MTX coadministered with folic or folinic acid (at least 5 mg/week)

• Subjects may remain on 1 nonsteroidal anti-inflammatory medication during the study (aspirin = 325 mg/day is allowed).

• Subjects must not have received prior treatment with a JAK inhibitor

• Subjects who are on an additional nonbiologic DMARD (e.g., sulfasalazine) must be willing to discontinue that DMARD after signing consent, except for hydroxychloroquine

• Subjects may have received previous therapy with a single TNF inhibitor (e.g., etanercept, adalimumab, infliximab, golimumab, certolizumab pegol)

• Females must have a negative pregnancy test prior to study dosing

• Sexually active subjects and their partners must agree to contraceptive requirements

Exclusion Criteria:

• History or presence of a clinically significant medical disorder other than RA 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.

• Subjects with inflammatory, rheumatological disorders other than RA

• Pregnant or nursing female subjects

• Subjects who have a female partner who is pregnant, nursing, or planning to become pregnant

• Subjects who have planned major surgery (e.g., joint replacement) or procedures during the study

• History of drug abuse or positive drug screen

• History of alcohol abuse or excessive alcohol consumption

• History of tuberculosis (TB) infection of any kind (pulmonary or extrapulmonary, active or latent), regardless of history of anti-TB treatment.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• VX-509
50 mg oral tablet
• VX-509 matching placebo
0 mg oral tablet

Locations

Country	Name	City	State
Argentina	Vertex Investigational Site	Buenos Aires
Argentina	Vertex Investigational Site	Buenos Aires
Argentina	Vertex Investigational Site	Buenos Aires
Argentina	Vertex Investigational Site	Santa Fe
Bulgaria	Vertex Investigational Site	Plovdiv
Bulgaria	Vertex Investigational Site	Sevlievo
Bulgaria	Vertex Investigational Site	Sofia
Bulgaria	Vertex Investigational Site	Sofia
Bulgaria	Vertex Investigational Site	Veliko Tarnovo
Czech Republic	Vertex Investigational Site	Brno
Czech Republic	Vertex Investigational Site	Bruntal
Czech Republic	Vertex Investigational Site	Mlada Boleslav
Czech Republic	Vertex Investigational Site	Ostrava - Trebovice
Czech Republic	Vertex Investigational Site	Praha 2
Czech Republic	Vertex Investigational Site	Zlin
Estonia	Vertex Investigational Site	Tallinn
Estonia	Vertex Investigational Site	Tallinn
Estonia	Vertex Investigational Site	Tallinn
Estonia	Vertex Investigational Site	Tallinn
Germany	Vertex Investigational Site	Koeln
Germany	Vertex Investigational Site	Leipzig
Germany	Vertex Investigational Site	Wuerzburg
Germany	Vertex Investigational Site	Zerbst
Hungary	Vertex Investigational Site	Baja
Hungary	Vertex Investigational Site	Budapest
Hungary	Vertex Investigational Site	Budapest
Hungary	Vertex Investigational Site	Szikszó
Mexico	Vertex Investigational Site	Chihuahua
Mexico	Vertex Investigational Site	Cuauhtemoc
Mexico	Vertex Investigational Site	San Luis Potos
Mexico	Vertex Investigational Site	San Miguel Chapultepec
Poland	Vertex Investigational Site	Bialystok
Poland	Vertex Investigational Site	Elblag
Poland	Vertex Investigational Site	Krakow
Poland	Vertex Investigational Site	Lublin
Poland	Vertex Investigational Site	Poznan
Poland	Vertex Investigational Site	Poznan
Poland	Vertex Investigational Site	Torun
Poland	Vertex Investigational Site	Warszawa
Poland	Vertex Investigational Site	Warszawa
Poland	Vertex Investigational Site	Warszawa
Romania	Vertex Investigational Site	Braila
Romania	Vertex Investigational Site	Bucuresti
Romania	Vertex Investigational Site	Bucuresti
Romania	Vertex Investigational Site	Judetul Galati
Russian Federation	Vertex Investigational Site	Kemerovo
Russian Federation	Vertex Investigational Site	Moscow
Russian Federation	Vertex Investigational Site	Ryazan
Russian Federation	Vertex Investigational Site	St. Petersburg
Russian Federation	Vertex Investigational Site	St. Petersburg
Russian Federation	Vertex Investigational Site	Yaroslavl
Serbia	Vertex Investigational Site	Belgrade
Serbia	Vertex Investigational Site	Niska Banja
Serbia	Vertex Investigational Site	Novi Sad
Slovakia	Vertex Investigational Site	Bratislava
Slovakia	Vertex Investigational Site	Dunajska Streda
Slovakia	Vertex Investigational Site	Poprad
Slovakia	Vertex Investigational Site	Rimavska Sobota
Ukraine	Vertex Investigational Site	Donetsk
Ukraine	Vertex Investigational Site	Kharkiv
Ukraine	Vertex Investigational Site	Lviv
Ukraine	Vertex Investigational Site	Odesa
Ukraine	Vertex Investigational Site	Vinnytsia
United States	Vertex Investigational Site	Austin	Texas
United States	Vertex Investigational Site	Bethlehem	Pennsylvania
United States	Vertex Investigational Site	Birmingham	Alabama
United States	Vertex Investigational Site	Boca Raton	Florida
United States	Vertex Investigational Site	Brooklyn	New York
United States	Vertex Investigational Site	Charlotte	North Carolina
United States	Vertex Investigational Site	Clarksburg	West Virginia
United States	Vertex Investigational Site	Clifton	New Jersey
United States	Vertex Investigational Site	Daytona Beach	Florida
United States	Vertex Investigational Site	Duncansville	Pennsylvania
United States	Vertex Investigational Site	Durham	North Carolina
United States	Vertex Investigational Site	Freehold	New Jersey
United States	Vertex Investigational Site	Hickory	North Carolina
United States	Vertex Investigational Site	Houston	Texas
United States	Vertex Investigational Site	Huntsville	Alabama
United States	Vertex Investigational Site	Jackson	Tennessee
United States	Vertex Investigational Site	Kalamazoo	Michigan
United States	Vertex Investigational Site	Las Vegas	Nevada
United States	Vertex Investigational Site	Long Beach	California
United States	Vertex Investigational Site	Mesquite	Texas
United States	Vertex Investigational Site	New Port Richey	Florida
United States	Vertex Investigational Site	North Miami Beach	Florida
United States	Vertex Investigational Site	Ocala	Florida
United States	Vertex Investigational Site	Oklahoma City	Oklahoma
United States	Vertex Investigational Site	Omaha	Nebraska
United States	Vertex Investigational Site	San Antonio	Texas
United States	Vertex Investigational Site	Springfield	Illinois
United States	Vertex Investigational Site	St. Louis	Missouri
United States	Vertex Investigational Site	Tampa	Florida
United States	Vertex Investigational Site	Tustin	California
United States	Vertex Investigational Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Czech Republic,  Estonia,  Germany,  Hungary,  Mexico,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects who achieve a 20% improvement in disease severity according to the American College of Rheumatology criteria, assessed using the C-reactive protein level (ACR20-CRP) response		Week 12	No
Primary	Change from baseline in Disease Activity Score 28 using C-reactive protein (DAS28- CRP)		Week 12	No
Primary	Safety and tolerability	Measured by incidence of treatment-emergent adverse events	Week 12	No
Primary	Safety and tolerability	Measured by clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis)	Week 12	No
Primary	Safety and tolerability	Measured by 12-lead ECG outcomes	Week 12	No
Primary	Safety and tolerability	Measured by vital signs	Week 12	No
Secondary	Proportion of subjects who achieve an ACR20-CRP response		Week 24	No
Secondary	Proportion of subjects who achieve ACR50-CRP and ACR70-CRP responses		Week 12 and 24	No
Secondary	Proportion of subjects who achieve a moderate or good response according to the European League Against Rheumatism (EULAR) response criteria		Week 12 and 24	No
Secondary	Proportion of subjects who achieve remission as defined by DAS28-CRP response		Week 12 and 24	No
Secondary	Proportion of subjects who achieve remission as defined by the ACR/EULAR definition of remission		Week 12 and 24	No
Secondary	Change from baseline in selected Patient Reported Outcomes (PROs)		Week 12 and 24	No
Secondary	Change from baseline in DAS28- CRP		Week 24	No
Secondary	Safety and tolerability as indicated by adverse events, hematology, clinical chemistry, coagulation, urinalysis, electrocardiograms (ECGs) and vital signs		Week 24	No