Clinical trial NCT01390545: VELVET, a Dose Range Finding Trial of Veltuzumab in Subjects With Moderate to Severe Rheumatoid Arthritis
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
anti-CD20 antibody
subcutaneous
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-07-11
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: American College of Rheumatology 20 (ACR20) response rate at completion of week 24
timeFrame: 24 weeks
Secondary outcomes:
measure: ACR50/70 response rate
timeFrame: 24 and 48 weeks
measure: ACR20 response rate
timeFrame: 48 weeks
measure: Further efficacy analyses (Hybrid ACR response, DAS28-CRP, EULAR response)
timeFrame: 24 and 48 weeks
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: Nycomed Investigational Site
state: California
city: Los Angeles
country: United States
facility: Nycomed Investigational Site
state: California
city: Upland
country: United States
facility: Nycomed Investigational Site
state: California
city: Aventura
country: United States
facility: Nycomed Investigational Site
state: Florida
city: Las Vegas
country: United States
facility: Nycomed Investigational Site
state: Nevada
city: Charleston
country: United States
facility: Nycomed Investigational Site
state: South Carolina
city: Nashville
country: United States
facility: Nycomed Investigational Site
state: Tennessee
city: San Antonio
country: United States
facility: Nycomed Investigational Site
state: Texas
city: Caba
country: Argentina
facility: Nycomed Investigational Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Nycomed Investigational Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Nycomed Investigational Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Nycomed Investigational Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Nycomed Investigational Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Nycomed Investigational Site
state: Buenos Aires
city: San Miguel de Tucumán
country: Argentina
facility: Nycomed Investigational Site
state: Tucumán
city: Córdoba
country: Argentina
facility: Nycomed Investigational Site
city: San Juan
country: Argentina
facility: Nycomed Investigational Site
city: Santa Fe
country: Argentina
facility: Nycomed Investigational Site
city: Calgary
country: Canada
facility: Nycomed Investigational Site
state: Alberta
city: Kitchener
country: Canada
facility: Nycomed Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: Nycomed Investigational Site
state: Ontario
city: St. Catharines
country: Canada
facility: Nycomed Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Nycomed Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: Nycomed Investigational Site
state: Ontario
city: Saskatoon
country: Canada
facility: Nycomed Investigational Site
state: Saskatchewan
city: Hlucin
country: Czech Republic
facility: Nycomed Investigational Site
city: Hostivice
country: Czech Republic
facility: Nycomed Investigational Site
city: Plzen
country: Czech Republic
facility: Nycomed Investigational Site
city: Praha 2
country: Czech Republic
facility: Nycomed Investigational Site
city: Uherske Hradiste
country: Czech Republic
facility: Nycomed Investigational Site
city: Zlin
country: Czech Republic
facility: Nycomed Investigational Site
city: Bad Nauheim
country: Germany
facility: Nycomed Investigational Site
city: Wuerzburg
country: Germany
facility: Nycomed Investigational Site
city: Debrecen
country: Hungary
facility: Nycomed Investigational Site
city: Kecskemét
country: Hungary
facility: Nycomed Investigational Site
city: Kiskunhaias
country: Hungary
facility: Nycomed Investigational Site
city: Kistarcsa
country: Hungary
facility: Nycomed Investigational Site
city: Mezőkövesd
country: Hungary
facility: Nycomed Investigational Site
city: Szekesfehervar
country: Hungary
facility: Nycomed Investigational Site
city: Szolnok
country: Hungary
facility: Nycomed Investigational Site
city: Arenzano (GE)
country: Italy
facility: Nycomed Investigational Site
city: Jesi (AN)
country: Italy
facility: Nycomed Investigational Site
city: Massa
country: Italy
facility: Nycomed Investigational Site
city: Valeggio S/M (VR)
country: Italy
facility: Nycomed Investigational Site
city: Guadalajara
country: Mexico
facility: Nycomed Investigational Site
state: Jalisco
city: Guadalajara
country: Mexico
facility: Nycomed Investigational Site
state: Jalisco
city: Distrito Federal
country: Mexico
facility: Nycomed Investigational Site
state: México
city: Monterrey
country: Mexico
facility: Nycomed Investigational Site
state: Nuevo León
city: Culiacan
country: Mexico
facility: Nycomed Investigational Site
state: Sinaloa
city: Mazatlán
country: Mexico
facility: Nycomed Investigational Site
state: Sinaloa
city: Ciudad Obregón
country: Mexico
facility: Nycomed Investigational Site
state: Sonora
city: Distrito Federal
country: Mexico
facility: Nycomed Investigational Site
city: Białystok
country: Poland
facility: Nycomed Investigational Site
city: Bydgoszcz
country: Poland
facility: Nycomed Investigational Site
city: Lublin
country: Poland
facility: Nycomed Investigational Site
city: Poznań
country: Poland
facility: Nycomed Investigational Site
city: Sopot
country: Poland
facility: Nycomed Investigational Site
city: Warsaw
country: Poland
facility: Nycomed Investigational Site
city: Sevilla
country: Spain
facility: Nycomed Investigational Site
state: Andalucía
city: Barakaldo
country: Spain
facility: Nycomed Investigational Site
state: Euskadi
city: A Coruña
country: Spain
facility: Nycomed Investigational Site
state: Galicia
city: Ashford
country: United Kingdom
facility: Nycomed Investigational Site
state: Middlesex
city: Barnsley
country: United Kingdom
facility: Nycomed Investigational Site
state: S. Yorkshire
Study officials:
References: