Rheumatoid ArthritisPhase 1NCT01123070

TL011 in Severe, Active Rheumatoid Arthritis Patients

A Phase 1 study testing TL011, anti CD20, for the treatment of rheumatoid arthritis and MabThera infusions in people with Rheumatoid Arthritis, run by Teva Pharmaceutical Industries, Ltd. at 18 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study is to determine the safety and pharmacology of TL011 in patients with severe rheumatoid arthritis. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: TL011, anti CD20, for the treatment of rheumatoid arthritis and MabThera infusions
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 54 participants
Where: 18 sitesin 5 countries
Study dates: 5 Feb 2010to 23 Apr 2012
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adult subjects
Rheumatoid arthritis as defined by the 1987 ACR Classification
Severe active seropositive disease
Inadequate response or intolerance to other DMARDs
Treatment with MTX

Who cannot join

Rheumatic autoimmune disease other than RA
Active infection
Known immunodeficiency syndrome
Positive Hepatitis B surface antigen or antibodies to Hepatitis C
History of cancer

Trial locations and contacts

18 sites in 5 countries.

Country

City, postcode or hospital

18 sites in 5 countries

Hungary4 sites

Teva Investigational Site 5123
Budapest, 1083
Teva Investigational Site 5122
Budapest, H-1023
Teva Investigational Site 5125
Debrecen, 4032
Teva Investigational Site 5124
Szeged, H-6720

Other trials in Hungary

Italy4 sites

Teva Investigational Site 3077
Florence, 50139
Teva Investigational Site 3075
Genova, 16132
Teva Investigational Site 3078
Pavia, 27100
Teva Investigational Site 3076
Siena, 53100

Other trials in Italy

Spain4 sites

Teva Investigational Site 3170
Barakaldo, 48903
Teva Investigational Site 3168
Guadalajara, 19002
Teva Investigational Site 3167
Madrid, 28009
Teva Investigational Site 3169
Seville, 41014

Other trials in Spain

Czechia3 sites

Teva Investigational Site 5428
Pilsen, 323 00
Teva Investigational Site 5426
Prague, 12850
Teva Investigational Site 5429
Uherské Hradiště, 686 01

Other trials in Czechia

United Kingdom3 sites

Teva Investigational Site 3434
Manchester, M13 9WL
Teva Investigational Site 3433
Staffordshire, WS11 5XY
Teva Investigational Site 3435
Wirral, Merseyside, CH49 5PE

Other trials in United Kingdom

About this study

Official title: A Phase Ib Study Evaluating Safety, Pharmacokinetic and Pharmacodynamic Profiles of a Single Course of TL011 Infusions in Subjects With Severe, Active Rheumatoid Arthritis

The purpose of this study is to determine the safety and pharmacology of TL011 in patients with severe rheumatoid arthritis.

Conditions: Rheumatoid Arthritis
Being tested: TL011, anti CD20, for the treatment of rheumatoid arthritis, MabThera infusions
Medical subject headings: Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TL011, anti CD20, for the treatment of rheumatoid arthritisBiological
TL011 administered by 2 infusions, 2 weeks apart
MabThera infusionsBiological
MabThera, administered by 2 infusions, 2 weeks apart

Study groups in NCT01123070
Study group	Role	What they receive
TL011	Experimental	TL011 infusions Receives: Biological: TL011, anti CD20, for the treatment of rheumatoid arthritis
MabThera	Active comparator	MabThera infusions Receives: Biological: MabThera infusions

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Plasma Concentration Versus Time Curve [AUC(0-t)] in Part B
Measured: Day 1 to Day 57

Secondary outcomes (8)

Maximum Observed Concentration (Cmax) in Part B
Measured: Day 1 to Day 57
Number of Participants With Adverse Events in Part B
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring after the first dose of the study drug until 120 days after the last dose of study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Measured: From randomization up to Week 24
Cmax Post First Dose (C1max) and Post Second Dose (C2max) in Part B
Measured: Day 1, Day 15
AUC At First Dose (AUC1) and AUC At Second Dose (AUC2) in Part B
Measured: Day 1, Day 15
Percent Change From Baseline in CD19+ B-cell Count in Part B
Measured: Baseline to Day 57
Number of Participants With American College of Rheumatology (ACR20) Criteria Response in Part B
Defined as at least 20% improvement from the screening values in swollen and tender joint count and in 3 of the following 5 disease activity measures.
- Physician's global assessment of disease activity (VAS)
- Patient's assessment of RA pain (VAS)
- Patient's global assessment of disease activity
- Patient's assessment of physical function (Health Assessment Questionnaire)
- Acute phase reactant (C-reactive protein [CRP])
Measured: Baseline to Day 57
Area Under the Plasma Concentration Versus Time Curve [AUC (0-t)] for Part A Cohort 2
Data available for cohort 2 only per planned analysis.
Measured: Day 1 to Day 57
Number of Participants With Adverse Events in Part A
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring after the first dose of the study drug until 120 days after the last dose of study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Measured: From randomization up to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Feb 201023 Apr 2012

First posted14 May 2010 (estimated)
Study start5 Feb 2010
Primary completion23 Apr 2012
Study completion23 Apr 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 54 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01123070
Sponsor's protocol ID: RA-TL011-101
Other IDs: 2009-015702-18, 2009
Status last verified: Sep 2021
First submitted: 11 May 2010
Last updated: 4 Oct 2021
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis

All Rheumatoid Arthritis trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase Ib Study Evaluating Safety, Pharmacokinetic and Pharmacodynamic Profiles of a Single Course of TL011 Infusions in Subjects With Severe, Active Rheumatoid Arthritis
ClinicalTrials.gov ID: NCT01123070
Acronym / sponsor ID: RA-TL011-101
Conditions: Rheumatoid Arthritis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 54 participants (actual)
Lead sponsor: Teva Pharmaceutical Industries, Ltd.Industry (pharma, biotech, devices)
Study start: 5 Feb 2010 (actual)
Primary completion: 23 Apr 2012 (actual)
Study completion: 23 Apr 2012 (actual)
First posted: 14 May 2010 (estimated)
Results: Posted 4 Oct 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to determine the safety and pharmacology of TL011 in patients with severe rheumatoid arthritis.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
TL011	Experimental	Biological: TL011, anti CD20, for the treatment of rheumatoid arthritisTL011 infusions
MabThera	Active comparator	Biological: MabThera infusionsMabThera infusions

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Adult subjects
Rheumatoid arthritis as defined by the 1987 ACR Classification
Severe active seropositive disease
Inadequate response or intolerance to other DMARDs
Treatment with MTX

Key exclusion criteria (5 listed)

Rheumatic autoimmune disease other than RA
Active infection
Known immunodeficiency syndrome
Positive Hepatitis B surface antigen or antibodies to Hepatitis C
History of cancer

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TL011, anti CD20, for the treatment of rheumatoid arthritisTL011 administered by 2 infusions, 2 weeks apart	Biological	TL011
MabThera infusionsMabThera, administered by 2 infusions, 2 weeks apart	Biological	MabThera

Primary outcome

Area Under the Plasma Concentration Versus Time Curve [AUC(0-t)] in Part B
Time frame: Day 1 to Day 57

8 secondary outcomes

Maximum Observed Concentration (Cmax) in Part B
Time frame: Day 1 to Day 57
Number of Participants With Adverse Events in Part B
Time frame: From randomization up to Week 24
Cmax Post First Dose (C1max) and Post Second Dose (C2max) in Part B
Time frame: Day 1, Day 15
AUC At First Dose (AUC1) and AUC At Second Dose (AUC2) in Part B
Time frame: Day 1, Day 15
Percent Change From Baseline in CD19+ B-cell Count in Part B
Time frame: Baseline to Day 57
Number of Participants With American College of Rheumatology (ACR20) Criteria Response in Part B
Time frame: Baseline to Day 57
Area Under the Plasma Concentration Versus Time Curve [AUC (0-t)] for Part A Cohort 2
Time frame: Day 1 to Day 57
Number of Participants With Adverse Events in Part A
Time frame: From randomization up to Week 24

Results and safety

Results posted to the registry on 4 Oct 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1 TL011 500 mg	3	3
Cohort 2 TL011 1000 mg	0	0
Double Blind TL011 1000 mg	0	0
Double Blind MabThera 1000 mg	0	0

Primary outcome: Area Under the Plasma Concentration Versus Time Curve [AUC(0-t)] in Part B

Time frame: Day 1 to Day 57. Geometric mean (Standard Deviation). Unit: Day*micrograms per milliliter

Measure	Double Blind TL011 1000 mg n = 21	Double Blind MabThera 1000 mg n = 18
Value	7571 (2219)	8377 (2879)

Double Blind TL011 1000 mg vs Double Blind MabThera 1000 mg: Geometric mean ratio: 0.930 (90% CI 0.797 to 1.084), p = 0.4265, ANCOVA

Population analysed: Pharmacokinetics (PK) population included all participants that received at least one dose of 1000 mg TL011 or MabThera and had sufficient plasma concentration results to allow estimation of PK parameters

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 24 weeks after first dose of study drug.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1 TL011 500 mg	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Cohort 2 TL011 1000 mg	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Double Blind TL011 1000 mg	1 of 25 (4%)	11 of 25 (44%)	0 of 25
Double Blind MabThera 1000 mg	1 of 23 (4.3%)	5 of 23 (21.7%)	0 of 23

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Rheumatoid Arthritis

RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

18 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Hungary, Italy, Spain, Czechia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Plasma Concentration Versus Time Curve [AUC(0-t)] in Part B (time frame: Day 1 to Day 57). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01123070.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2021.