A clinical study to explore the therapeutic effects of different doses of the new drug veltuzumab, a drug of biologic origin, and placebo, in patients with rheumatoid arthritis.

• Register: EUCTR
• Last refreshed on: 29 October 2012
• Main ID: EUCTR2010-022378-15-ES
• Date of registration: 21/02/2011
• Prospective Registration: Yes
• Primary sponsor: Nycomed GmbH
• Public title: A clinical study to explore the therapeutic effects of different doses of the new drug veltuzumab, a drug of biologic origin, and placebo, in patients with rheumatoid arthritis.
• Scientific 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. - VELVET
• Date of first enrolment: 19/05/2011
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022378-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

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

Contacts

• Name: Clinical trial operations
• Affiliation: Nycomed GmbH

• Name: Clinical trial operations
• Affiliation: Nycomed GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
- Written informed consent obtained before any trial-related activities
- Outpatient, male or female, at least 18 years of age at Screening
- Active rheumatoid arthritis. Diagnosis of RA using the ACR criteria for
the classification of RA for at least 6 months prior to trial entry (based
on swollen and tender joint count; CRP and/or ESR; RF and/or anti-CCP)
- An inadequate response to previous or current treatment with either
MTX alone or a combination of MTX plus anti-tumor necrosis factor alpha
biologic agents.
- Receiving MTX 15-25 mg/week (oral or parenteral) for at least 20
weeks, including the last 6 weeks prior to Baseline at a stable dose
- Subjects of reproductive potential (females and males) must agree to
use effective double-method contraception
- Female subjects must not be actively breast-feeding
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 210
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion criteria:
Medical history/concurrent diseases
Joints
- Subjects who are wheel chair or bed bound
- Rheumatic autoimmune disease other than RA, or significant systemic
involvement secondary to RA
- History of or current inflammatory joint disease other than RA
- Septic prosthetic joint within the last 48 weeks prior to Baseline or
indefinitely if the prosthesis concerned remains in situ.
Infectious diseases
- Primary or secondary immunodeficiency, including human
immunodeficiency virus (HIV) infection
- Evidence of acute or chronic infection with hepatitis B virus (HBV) or
hepatitis C virus (HCV)
- Evidence and/or history of active tuberculosis (TB), prior to
successfully completing an anti-TB treatment. Subjects with latent TB
infection (LTBI) can be included
- Acute clinical manifestations of herpes zoster virus and history of
severe herpes zoster
- History of active infection of any kind or any major episode of infection
requiring hospitalisation or treatment with iv anti infective agents within
6 weeks prior to Baseline or oral anti-infective agents within 2 weeks
prior to Baseline
- History of deep space/tissue infection within 48 weeks prior to
Baseline
- History of osteomyelitis
- History of sepsis of any origin requiring intensive care
- History of serious recurrent or chronic infections not specified above.
Cardio-pulmonary
- Any significant cardiac disease
- History of severe chronic obstructive pulmonary disease (COPD)
and/or history of severe COPD exacerbation(s) within the last 12
months prior to Screening .
Immune system/haematology/biochemistry
- History of a severe allergic reaction or anaphylactic reaction to a
biological agent or history of hypersensitivity to any component of
veltuzumab injection solution
- Subjects with CD4 cell counts (< 250/?l) at Screening
- Hypogammaglobulinemia (IgG < 5.0 g/L, and/or IgM < 0.20 g/L) at
Screening
- Splenectomy
- Subjects with haemoglobin < 9.0 g/dL, white blood cell (WBC) count <
3000 cells/?L, absolute neutrophil count (ANC) < 2000 cells/?L,
lymphocyte count < 800 cells/?L or platelet count < 100,000/?L at
Screening
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT),
gamma-glutamyl transpeptidase (GGT) or alkaline phosphatase levels >
2.0 times the upper limit of normal (ULNR) at Screening
- Subjects with a serum creatinine > ULNR (e.g. > 1.2 mg/dL for males
and > 1.0 mg/dL for females) at Screening
Other medical conditions
- Subjects with diabetes mellitus type 1 or unstable type 2
- History of solid-organ transplantation
- History of cancer within the last 5 years treated with anti-cancer
chemotherapy
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- Current active alcohol or drug abuse or history of alcohol or drug abuse
within 24 weeks prior to Baseline. Opiate-containing medicines are not
allowed
- Evidence of any significant and/or unstable concomitant diseases such
as nervous system, renal, hepatic, endocrine, respiratory or
gastrointestinal disorders which, in the Investigator's opinion, would
preclude subject participation
- Any other medical condition (e.g. clinically relevant abnormal
laboratory values) that would, in the Investigator's opinion, make the
administration of trial drug or trial procedures hazardous to the subject,
or obscure the interpretation of AEs.
Skin
- Chronic skin ulcerations.
Previous and concomitant therapies and procedures
- Any planned, elective or emergency surgical procedure, including bone
or joint surgery/synovectomy wit

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Rheumatoid Arthritis
MedDRA version: 14.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: Veltuzumab solution 75mg/ml
Product Code: hA20 (Immu-106)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Veltuzumab
CAS Number: 728917-18-8
Current Sponsor code: hA20, IMMU-106
Other descriptive name: humanised anti-CD 20 antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 70-80
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: To identify the dosage(s) of veltuzumab with the most favourable
benefit-risk-ratio to be further evaluated in the subsequent Phase II/III
clinical program in patients with moderate to severe RA

Primary end point(s): The primary efficacy variable will be the ACR20 responder rate after 24
weeks of double blind treatment with the study medication. Responders
will be defined as those whose improvement from baseline to endpoint
fullfil the following criteria:
- more or equal to 20% reduction in the TJC (66/68)
- more or equal to 20% reduction in the SJC (66/68)
- more or equal to 20% reduction in three of the following additional
measures:
- Subject assessment of pain (visual analogue scale [VAS])
- Subject global assessment of disease activity (VAS)
- Physician global assessment of disease activity (VAS)
- Degree of disability (HAQ-DI)
- Level of acute-phase reactant (CRP)

Main Objective: To investigate the efficacy and safety of three different sc doses of the
humanized anti-CD20 antibody veltuzumab as an add-on treatment to
MTX over 24 weeks compared to MTX alone

Timepoint(s) of evaluation of this end point: Week 24

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Various times points

Secondary end point(s): ACR20 response rate at week 48, ACR50 and ACR70 response rate at
week 24 and 48. Major clinical response. Safety parameters,
Pharmacokinetic parameters, Pharmacodynamic/Exploratory
biomarkers.

Secondary ID(s)

VT-4001-001-SP

2010-022378-15-DE

Source(s) of Monetary Support

Nycomed GmbH