VELVET, a Dose Range Finding Trial of Veltuzumab in Subjects With Moderate to Severe Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— VELVET  

Official title:

VELVET (Veltuzumab Various Doses Exploratory Trial), a Randomized, Double Blind, Placebo Controlled, Multicentre, Multinational Phase II Dose Range Finding Trial in Subjects With Moderate to Severe Rheumatoid Arthritis Insufficiently Controlled With Either Methotrexate Alone or Methotrexate Plus Anti-tumour Necrosis Factor Biological Treatment, Comparing 3 Different Subcutaneous Dosages of Anti-CD20 Monoclonal Antibody Veltuzumab to Placebo as an add-on Therapy to Methotrexate.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01390545
• Other study ID #: VT-4001-001-SP
• Secondary ID: 2010-022378-15U1
• Status: Terminated
• Phase: Phase 2
• First received: July 5, 2011
• Last updated: October 24, 2012
• Start date: August 2011
• Est. completion date: October 2012

Study information

• Verified date: October 2012
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaCanada: Health CanadaCzech Republic: State Institute for Drug ControlGermany: Paul-Ehrlich-InstitutHungary: National Institute of PharmacyItaly: The Italian Medicines AgencyMexico: Federal Commission for Protection Against Health RisksPoland: Ministry of HealthSpain: Agencia Española de Medicamentos y Productos SanitariosUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a multi-national, multi-centre, placebo-controlled, double-blind, randomized, 4-arm parallel group trial, comparing three different dose levels (80 mg, 160 mg and 320 mg) of veltuzumab to placebo, administered weekly (days 1, 8, 15 and 22) by subcutaneous (sc) injection to subjects with moderate to severe rheumatoid arthritis (RA) (cumulative veltuzumab doses 320 mg, 640 mg, and 1280 mg, respectively). All subjects will be on continued stable co-medication with methotrexate (MTX).

Description:

The trial comprises a screening phase (4 to 12 weeks prior to first administration of veltuzumab), a 4-week treatment phase (weeks 1 to 4), a core phase from week 4 to week 24, and a follow-up phase from week 24 to week 48. The primary end-point, the American College of Rheumatology 20 (ACR 20) response rate, will be evaluated at week 24.

The objectives of this trial are:

• To investigate the efficacy, safety and tolerability at week 24 of three different sc dose levels of the humanized anti-CD20 antibody veltuzumab as an add-on treatment to MTX compared to MTX alone in subjects with moderate to severe RA

• To evaluate the durability of the clinical response and safety of veltuzumab over 48 weeks

• To identify the dosage(s) of veltuzumab with the most favourable benefit-risk profile to be further evaluated in the subsequent phase II/III clinical program in subjects with moderate to severe RA.

Current status of the trial: Following the voluntary temporary halt of the VELVET dose range finding trial, the sponsor has decided to redesign the protocol and start a new trial as soon as possible.

All patients treated prior to the voluntary halt have completed their safety assessments. It was decided to terminate the VELVET trial and consequently not to recommence enrollment.

In the VELVET trial, a total of 11 patients received trial medication prior to the voluntary temporary halt. No efficacy conclusions according to protocol can be drawn from the 11 patients treated. Based on the collected clinical data from this trial, there is no clinical safety signal and no increased clinical safety risk observed to date that precludes continued clinical investigation of veltuzumab.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 300
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Main Inclusion Criteria:

• Active disease defined as:

• Diagnosis of RA using the ACR criteria for the classification of RA for at least 6 months prior to trial entry (Screening, Visit 1)

• Swollen joint count (SJC) = 6 and tender joint count (TJC) = 6 referred to as the 66/68 - joint count system

• High sensitivity C-reactive protein (hs-CRP) = 15 mg/L and/or an erythrocyte sedimentation rate (ESR) = 28 mm/hour

• Positive rheumatoid factor (RF) = 14 IU/mL and/or anti-cyclic citrullinated protein (CCP) = 20 U

• An inadequate response (insufficient initial or loss of response and/or intolerance to at least one administration of these agents) to previous or current treatment with either MTX alone or MTX plus anti-tumour necrosis factor alpha (anti-TNFa) biological treatment. Subjects should not have received more than two different anti-TNFa therapies.

• Receiving MTX 15-25 mg/week (oral or parenteral) for at least 20 weeks, including the last 6 weeks prior to Baseline (Visit 3, Day 1) at a stable dose via the same route of administration and formulation. A stable dose of 12.5 mg of MTX is acceptable if the MTX dose has been reduced for reasons of toxicity, e.g. pulmonary, hepatic or haematological toxicity. MTX co-medication will be continued until the end of the trial (Week 48)

Main Exclusion Criteria:

• Primary or secondary immunodeficiency including HIV infection

• Evidence of acute or chronic infection with hepatitis B and C virus (HBV and HCV)

• Evidence (e.g. chest X-ray [posterior-anterior view], tuberculin/ PPD skin test, etc., according local guidelines) and/or history of active tuberculosis (TB), prior to successfully completing an anti-TB treatment. X-rays performed prior to inclusion (Screening, Visit 1) into the trial are accepted provided they were done within 3 months prior to Screening (Visit 1). Subjects with latent TB infection (LTBI) can be included

• Significant cardiac disease or history of severe COPD

• Diabetes mellitus type 1 or unstable type 2

• History of cancer within the last 5 years treated with anti-cancer chemotherapy

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Veltuzumab
administered once weekly (days 1, 8, 15 and 22) by subcutaneous injection

Locations

Country	Name	City	State
Argentina	Nycomed Investigational Site	Caba	Buenos Aires
Argentina	Nycomed Investigational Site	Caba	Buenos Aires
Argentina	Nycomed Investigational Site	Caba	Buenos Aires
Argentina	Nycomed Investigational Site	Caba	Buenos Aires
Argentina	Nycomed Investigational Site	Caba	Buenos Aires
Argentina	Nycomed Investigational Site	Caba	Buenos Aires
Argentina	Nycomed Investigational Site	Córdoba
Argentina	Nycomed Investigational Site	San Juan
Argentina	Nycomed Investigational Site	San Miguel de Tucumán	Tucumán
Argentina	Nycomed Investigational Site	Santa Fe
Canada	Nycomed Investigational Site	Calgary	Alberta
Canada	Nycomed Investigational Site	Kitchener	Ontario
Canada	Nycomed Investigational Site	Ottawa	Ontario
Canada	Nycomed Investigational Site	Saskatoon	Saskatchewan
Canada	Nycomed Investigational Site	St. Catharines	Ontario
Canada	Nycomed Investigational Site	Toronto	Ontario
Canada	Nycomed Investigational Site	Windsor	Ontario
Czech Republic	Nycomed Investigational Site	Hlucin
Czech Republic	Nycomed Investigational Site	Hostivice
Czech Republic	Nycomed Investigational Site	Plzen
Czech Republic	Nycomed Investigational Site	Praha 2
Czech Republic	Nycomed Investigational Site	Uherske Hradiste
Czech Republic	Nycomed Investigational Site	Zlin
Germany	Nycomed Investigational Site	Bad Nauheim
Germany	Nycomed Investigational Site	Wuerzburg
Hungary	Nycomed Investigational Site	Debrecen
Hungary	Nycomed Investigational Site	Kecskemét
Hungary	Nycomed Investigational Site	Kiskunhaias
Hungary	Nycomed Investigational Site	Kistarcsa
Hungary	Nycomed Investigational Site	Mezokövesd
Hungary	Nycomed Investigational Site	Szekesfehervar
Hungary	Nycomed Investigational Site	Szolnok
Italy	Nycomed Investigational Site	Arenzano (GE)
Italy	Nycomed Investigational Site	Jesi (AN)
Italy	Nycomed Investigational Site	Massa
Italy	Nycomed Investigational Site	Valeggio S/M (VR)
Mexico	Nycomed Investigational Site	Ciudad Obregón	Sonora
Mexico	Nycomed Investigational Site	Culiacan	Sinaloa
Mexico	Nycomed Investigational Site	Distrito Federal	México
Mexico	Nycomed Investigational Site	Distrito Federal
Mexico	Nycomed Investigational Site	Guadalajara	Jalisco
Mexico	Nycomed Investigational Site	Guadalajara	Jalisco
Mexico	Nycomed Investigational Site	Mazatlán	Sinaloa
Mexico	Nycomed Investigational Site	Monterrey	Nuevo León
Poland	Nycomed Investigational Site	Bialystok
Poland	Nycomed Investigational Site	Bydgoszcz
Poland	Nycomed Investigational Site	Lublin
Poland	Nycomed Investigational Site	Poznan
Poland	Nycomed Investigational Site	Sopot
Poland	Nycomed Investigational Site	Warsaw
Spain	Nycomed Investigational Site	A Coruña	Galicia
Spain	Nycomed Investigational Site	Barakaldo	Euskadi
Spain	Nycomed Investigational Site	Sevilla	Andalucía
United Kingdom	Nycomed Investigational Site	Ashford	Middlesex
United Kingdom	Nycomed Investigational Site	Barnsley	S. Yorkshire
United States	Nycomed Investigational Site	Aventura	Florida
United States	Nycomed Investigational Site	Charleston	South Carolina
United States	Nycomed Investigational Site	La Mesa	California
United States	Nycomed Investigational Site	Las Vegas	Nevada
United States	Nycomed Investigational Site	Los Angeles	California
United States	Nycomed Investigational Site	Nashville	Tennessee
United States	Nycomed Investigational Site	San Antonio	Texas
United States	Nycomed Investigational Site	Upland	California

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Czech Republic,  Germany,  Hungary,  Italy,  Mexico,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	American College of Rheumatology 20 (ACR20) response rate at completion of week 24	ACR20 response rate is defined as improvement from baseline to endpoint fulfilling the following criteria: = 20 percent reduction in the Tender joint count (TJC) (66/68 joint count system); = 20 percent reduction in the Swollen joint count (SJC) (66/68 joint count system); = 20 percent reduction in three of the following additional measures: Patient's assessment of pain; Patient's global assessment of disease activity; Physician's global assessment of disease activity; Degree of disability; Level of acute-phase reactant (CRP)	24 weeks	No
Secondary	ACR50/70 response rate	ACR50/70 response rate is defined as improvement from baseline to endpoint fulfilling the following criteria: 50/70 percent reduction in the TJC (66/68 joint count system); 50/70 percent reduction in the SJC (66/68 joint count system); 50/70 percent in three of the following additional measures: Patient's assessment of pain; Patient's global assessment of disease activity; Physician's global assessment of disease activity; Degree of disability; Level of acute-phase reactant (CRP)	24 and 48 weeks	No
Secondary	ACR20 response rate	ACR20 response rate is defined as improvement from baseline to endpoint fulfilling the following criteria: 20 percent reduction in the TJC (66/68 joint count system); 20 percent reduction in the SJC (66/68 joint count system); 20 percent reduction in three of the following additional measures: Patient's assessment of pain; Patient's global assessment of disease activity; Physician's global assessment of disease activity; Degree of disability; Level of acute-phase reactant (CRP)	48 weeks	No
Secondary	Further efficacy analyses (Hybrid ACR response, DAS28-CRP, EULAR response)	To further demonstrate efficacy of veltuzumab	24 and 48 weeks	No