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

Sponsor

Takeda (Industry)

Overall Status

Terminated

CT.gov ID

NCT01390545

Collaborator

(none)

300

Enrollment

Locations

Arms

Duration (Months)

4.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Veltuzumab	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, 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.

Study Start Date :

Aug 1, 2011

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

American College of Rheumatology 20 (ACR20) response rate at completion of week 24 [24 weeks]
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 [24 and 48 weeks]
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 [48 weeks]
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) [24 and 48 weeks]
To further demonstrate efficacy of veltuzumab

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Nycomed Investigational Site	La Mesa	California	United States
2	Nycomed Investigational Site	Los Angeles	California	United States
3	Nycomed Investigational Site	Upland	California	United States
4	Nycomed Investigational Site	Aventura	Florida	United States
5	Nycomed Investigational Site	Las Vegas	Nevada	United States
6	Nycomed Investigational Site	Charleston	South Carolina	United States
7	Nycomed Investigational Site	Nashville	Tennessee	United States
8	Nycomed Investigational Site	San Antonio	Texas	United States
9	Nycomed Investigational Site	Caba	Buenos Aires	Argentina	C1015ABO
10	Nycomed Investigational Site	Caba	Buenos Aires	Argentina	C1114AAH
11	Nycomed Investigational Site	Caba	Buenos Aires	Argentina	C1419AHN
12	Nycomed Investigational Site	Caba	Buenos Aires	Argentina	C1425DQK
13	Nycomed Investigational Site	Caba	Buenos Aires	Argentina	C1425DTG
14	Nycomed Investigational Site	Caba	Buenos Aires	Argentina	C1426AAL
15	Nycomed Investigational Site	San Miguel de Tucumán	Tucumán	Argentina	T4000AXL
16	Nycomed Investigational Site	Córdoba		Argentina	X5016KEH
17	Nycomed Investigational Site	San Juan		Argentina	J5402DKL
18	Nycomed Investigational Site	Santa Fe		Argentina	S3000FWO
19	Nycomed Investigational Site	Calgary	Alberta	Canada
20	Nycomed Investigational Site	Kitchener	Ontario	Canada
21	Nycomed Investigational Site	Ottawa	Ontario	Canada
22	Nycomed Investigational Site	St. Catharines	Ontario	Canada
23	Nycomed Investigational Site	Toronto	Ontario	Canada
24	Nycomed Investigational Site	Windsor	Ontario	Canada
25	Nycomed Investigational Site	Saskatoon	Saskatchewan	Canada
26	Nycomed Investigational Site	Hlucin		Czech Republic
27	Nycomed Investigational Site	Hostivice		Czech Republic
28	Nycomed Investigational Site	Plzen		Czech Republic
29	Nycomed Investigational Site	Praha 2		Czech Republic
30	Nycomed Investigational Site	Uherske Hradiste		Czech Republic
31	Nycomed Investigational Site	Zlin		Czech Republic
32	Nycomed Investigational Site	Bad Nauheim		Germany
33	Nycomed Investigational Site	Wuerzburg		Germany
34	Nycomed Investigational Site	Debrecen		Hungary
35	Nycomed Investigational Site	Kecskemét		Hungary
36	Nycomed Investigational Site	Kiskunhaias		Hungary
37	Nycomed Investigational Site	Kistarcsa		Hungary
38	Nycomed Investigational Site	Mezőkövesd		Hungary
39	Nycomed Investigational Site	Szekesfehervar		Hungary
40	Nycomed Investigational Site	Szolnok		Hungary
41	Nycomed Investigational Site	Arenzano (GE)		Italy
42	Nycomed Investigational Site	Jesi (AN)		Italy
43	Nycomed Investigational Site	Massa		Italy
44	Nycomed Investigational Site	Valeggio S/M (VR)		Italy
45	Nycomed Investigational Site	Guadalajara	Jalisco	Mexico	44185
46	Nycomed Investigational Site	Guadalajara	Jalisco	Mexico	44620
47	Nycomed Investigational Site	Distrito Federal	México	Mexico	06700
48	Nycomed Investigational Site	Monterrey	Nuevo León	Mexico	64460
49	Nycomed Investigational Site	Culiacan	Sinaloa	Mexico	80020
50	Nycomed Investigational Site	Mazatlán	Sinaloa	Mexico	82126
51	Nycomed Investigational Site	Ciudad Obregón	Sonora	Mexico	85000
52	Nycomed Investigational Site	Distrito Federal		Mexico	06700
53	Nycomed Investigational Site	Białystok		Poland
54	Nycomed Investigational Site	Bydgoszcz		Poland
55	Nycomed Investigational Site	Lublin		Poland
56	Nycomed Investigational Site	Poznań		Poland
57	Nycomed Investigational Site	Sopot		Poland
58	Nycomed Investigational Site	Warsaw		Poland
59	Nycomed Investigational Site	Sevilla	Andalucía	Spain
60	Nycomed Investigational Site	Barakaldo	Euskadi	Spain
61	Nycomed Investigational Site	A Coruña	Galicia	Spain
62	Nycomed Investigational Site	Ashford	Middlesex	United Kingdom
63	Nycomed Investigational Site	Barnsley	S. Yorkshire	United Kingdom