Back to resultsVELVET, a Dose Range Finding Trial of Veltuzumab in Subjects With Moderate to Severe Rheumatoid Arthritis (VELVET)
Primary Purpose
Rheumatoid Arthritis
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Veltuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, anti-CD20 antibody, subcutaneous
Eligibility Criteria
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-TNFα) biological treatment. Subjects should not have received more than two different anti-TNFα 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
Sites / Locations
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
- Nycomed Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Veltuzumab 80 mg
Veltuzumab 160 mg
Veltuzumab 320 mg
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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)
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)
Further efficacy analyses (Hybrid ACR response, DAS28-CRP, EULAR response)
To further demonstrate efficacy of veltuzumab
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01390545
Brief Title
VELVET, a Dose Range Finding Trial of Veltuzumab in Subjects With Moderate to Severe Rheumatoid Arthritis
Acronym
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.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Terminated
Why Stopped
Trial re-design; no safety issues identified
Study Start Date
August 2011 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
October 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
5. Study Description
Brief 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).
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid arthritis, anti-CD20 antibody, subcutaneous
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Veltuzumab 80 mg
Arm Type
Active Comparator
Arm Title
Veltuzumab 160 mg
Arm Type
Active Comparator
Arm Title
Veltuzumab 320 mg
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Veltuzumab
Intervention Description
administered once weekly (days 1, 8, 15 and 22) by subcutaneous injection
Primary Outcome Measure Information:
Title
American College of Rheumatology 20 (ACR20) response rate at completion of week 24
Description
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)
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
ACR50/70 response rate
Description
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)
Time Frame
24 and 48 weeks
Title
ACR20 response rate
Description
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)
Time Frame
48 weeks
Title
Further efficacy analyses (Hybrid ACR response, DAS28-CRP, EULAR response)
Description
To further demonstrate efficacy of veltuzumab
Time Frame
24 and 48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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-TNFα) biological treatment. Subjects should not have received more than two different anti-TNFα 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
Facility Information:
Facility Name
Nycomed Investigational Site
City
La Mesa
State/Province
California
Country
United States
Facility Name
Nycomed Investigational Site
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Nycomed Investigational Site
City
Upland
State/Province
California
Country
United States
Facility Name
Nycomed Investigational Site
City
Aventura
State/Province
Florida
Country
United States
Facility Name
Nycomed Investigational Site
City
Las Vegas
State/Province
Nevada
Country
United States
Facility Name
Nycomed Investigational Site
City
Charleston
State/Province
South Carolina
Country
United States
Facility Name
Nycomed Investigational Site
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Nycomed Investigational Site
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
Nycomed Investigational Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1015ABO
Country
Argentina
Facility Name
Nycomed Investigational Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1114AAH
Country
Argentina
Facility Name
Nycomed Investigational Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1419AHN
Country
Argentina
Facility Name
Nycomed Investigational Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1425DQK
Country
Argentina
Facility Name
Nycomed Investigational Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1425DTG
Country
Argentina
Facility Name
Nycomed Investigational Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1426AAL
Country
Argentina
Facility Name
Nycomed Investigational Site
City
San Miguel de Tucumán
State/Province
Tucumán
ZIP/Postal Code
T4000AXL
Country
Argentina
Facility Name
Nycomed Investigational Site
City
Córdoba
ZIP/Postal Code
X5016KEH
Country
Argentina
Facility Name
Nycomed Investigational Site
City
San Juan
ZIP/Postal Code
J5402DKL
Country
Argentina
Facility Name
Nycomed Investigational Site
City
Santa Fe
ZIP/Postal Code
S3000FWO
Country
Argentina
Facility Name
Nycomed Investigational Site
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
Nycomed Investigational Site
City
Kitchener
State/Province
Ontario
Country
Canada
Facility Name
Nycomed Investigational Site
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
Nycomed Investigational Site
City
St. Catharines
State/Province
Ontario
Country
Canada
Facility Name
Nycomed Investigational Site
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Nycomed Investigational Site
City
Windsor
State/Province
Ontario
Country
Canada
Facility Name
Nycomed Investigational Site
City
Saskatoon
State/Province
Saskatchewan
Country
Canada
Facility Name
Nycomed Investigational Site
City
Hlucin
Country
Czech Republic
Facility Name
Nycomed Investigational Site
City
Hostivice
Country
Czech Republic
Facility Name
Nycomed Investigational Site
City
Plzen
Country
Czech Republic
Facility Name
Nycomed Investigational Site
City
Praha 2
Country
Czech Republic
Facility Name
Nycomed Investigational Site
City
Uherske Hradiste
Country
Czech Republic
Facility Name
Nycomed Investigational Site
City
Zlin
Country
Czech Republic
Facility Name
Nycomed Investigational Site
City
Bad Nauheim
Country
Germany
Facility Name
Nycomed Investigational Site
City
Wuerzburg
Country
Germany
Facility Name
Nycomed Investigational Site
City
Debrecen
Country
Hungary
Facility Name
Nycomed Investigational Site
City
Kecskemét
Country
Hungary
Facility Name
Nycomed Investigational Site
City
Kiskunhaias
Country
Hungary
Facility Name
Nycomed Investigational Site
City
Kistarcsa
Country
Hungary
Facility Name
Nycomed Investigational Site
City
Mezőkövesd
Country
Hungary
Facility Name
Nycomed Investigational Site
City
Szekesfehervar
Country
Hungary
Facility Name
Nycomed Investigational Site
City
Szolnok
Country
Hungary
Facility Name
Nycomed Investigational Site
City
Arenzano (GE)
Country
Italy
Facility Name
Nycomed Investigational Site
City
Jesi (AN)
Country
Italy
Facility Name
Nycomed Investigational Site
City
Massa
Country
Italy
Facility Name
Nycomed Investigational Site
City
Valeggio S/M (VR)
Country
Italy
Facility Name
Nycomed Investigational Site
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44185
Country
Mexico
Facility Name
Nycomed Investigational Site
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44620
Country
Mexico
Facility Name
Nycomed Investigational Site
City
Distrito Federal
State/Province
México
ZIP/Postal Code
06700
Country
Mexico
Facility Name
Nycomed Investigational Site
City
Monterrey
State/Province
Nuevo León
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Nycomed Investigational Site
City
Culiacan
State/Province
Sinaloa
ZIP/Postal Code
80020
Country
Mexico
Facility Name
Nycomed Investigational Site
City
Mazatlán
State/Province
Sinaloa
ZIP/Postal Code
82126
Country
Mexico
Facility Name
Nycomed Investigational Site
City
Ciudad Obregón
State/Province
Sonora
ZIP/Postal Code
85000
Country
Mexico
Facility Name
Nycomed Investigational Site
City
Distrito Federal
ZIP/Postal Code
06700
Country
Mexico
Facility Name
Nycomed Investigational Site
City
Białystok
Country
Poland
Facility Name
Nycomed Investigational Site
City
Bydgoszcz
Country
Poland
Facility Name
Nycomed Investigational Site
City
Lublin
Country
Poland
Facility Name
Nycomed Investigational Site
City
Poznań
Country
Poland
Facility Name
Nycomed Investigational Site
City
Sopot
Country
Poland
Facility Name
Nycomed Investigational Site
City
Warsaw
Country
Poland
Facility Name
Nycomed Investigational Site
City
Sevilla
State/Province
Andalucía
Country
Spain
Facility Name
Nycomed Investigational Site
City
Barakaldo
State/Province
Euskadi
Country
Spain
Facility Name
Nycomed Investigational Site
City
A Coruña
State/Province
Galicia
Country
Spain
Facility Name
Nycomed Investigational Site
City
Ashford
State/Province
Middlesex
Country
United Kingdom
Facility Name
Nycomed Investigational Site
City
Barnsley
State/Province
S. Yorkshire
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
VELVET, a Dose Range Finding Trial of Veltuzumab in Subjects With Moderate to Severe Rheumatoid Arthritis
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