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

This study has been terminated.
(Trial re-design; no safety issues identified)
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01390545
First received: July 5, 2011
Last updated: October 24, 2012
Last verified: October 2012
  Purpose

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).


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Veltuzumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • American College of Rheumatology 20 (ACR20) response rate at completion of week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

    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 [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]

    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 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

    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) [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
    To further demonstrate efficacy of veltuzumab


Estimated Enrollment: 300
Study Start Date: August 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Veltuzumab 80 mg Drug: Veltuzumab
administered once weekly (days 1, 8, 15 and 22) by subcutaneous injection
Active Comparator: Veltuzumab 160 mg Drug: Veltuzumab
administered once weekly (days 1, 8, 15 and 22) by subcutaneous injection
Active Comparator: Veltuzumab 320 mg Drug: Veltuzumab
administered once weekly (days 1, 8, 15 and 22) by subcutaneous injection
Placebo Comparator: Placebo Drug: Veltuzumab
administered once weekly (days 1, 8, 15 and 22) by subcutaneous injection

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01390545

  Show 63 Study Locations
Sponsors and Collaborators
Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01390545     History of Changes
Other Study ID Numbers: VT-4001-001-SP, 2010-022378-15, U1111-1136-3415
Study First Received: July 5, 2011
Last Updated: October 24, 2012
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Germany: Paul-Ehrlich-Institut
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Mexico: Federal Commission for Protection Against Health Risks
Poland: Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Takeda:
Rheumatoid arthritis
anti-CD20 antibody
subcutaneous

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 18, 2014