Trial Outcomes & Findings for TL011 in Severe, Active Rheumatoid Arthritis Patients (NCT NCT01123070)
NCT ID: NCT01123070
Last Updated: 2021-10-04
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
54 participants
Primary outcome timeframe
Day 1 to Day 57
Results posted on
2021-10-04
Participant Flow
Part A was an open label dose escalation for TL011 with two cohorts. Part B was randomized, double blind with two treatment groups to compare TL011 to MabThera. There was an 8 weeks core study period followed by 16 weeks extended follow up period.
Participant milestones
| Measure |
Cohort 1 TL011 500 mg
Participants were administered 500 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Cohort 2 TL011 1000 mg
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind TL011 1000 mg
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|---|---|
|
Part A Cohort 1 Open Label Period
STARTED
|
3
|
0
|
0
|
0
|
|
Part A Cohort 1 Open Label Period
COMPLETED
|
3
|
0
|
0
|
0
|
|
Part A Cohort 1 Open Label Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Part A Cohort 2 Open Label Period
STARTED
|
0
|
3
|
0
|
0
|
|
Part A Cohort 2 Open Label Period
COMPLETED
|
0
|
3
|
0
|
0
|
|
Part A Cohort 2 Open Label Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Part B Double Blind Period
STARTED
|
0
|
0
|
25
|
23
|
|
Part B Double Blind Period
COMPLETED
|
0
|
0
|
21
|
20
|
|
Part B Double Blind Period
NOT COMPLETED
|
0
|
0
|
4
|
3
|
Reasons for withdrawal
| Measure |
Cohort 1 TL011 500 mg
Participants were administered 500 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Cohort 2 TL011 1000 mg
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind TL011 1000 mg
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|---|---|
|
Part B Double Blind Period
Protocol Violation
|
0
|
0
|
0
|
1
|
|
Part B Double Blind Period
Adverse Event
|
0
|
0
|
2
|
0
|
|
Part B Double Blind Period
Sponsor's Decision
|
0
|
0
|
2
|
2
|
Baseline Characteristics
TL011 in Severe, Active Rheumatoid Arthritis Patients
Baseline characteristics by cohort
| Measure |
Cohort 1 TL011 500 mg
n=3 Participants
Participants were administered 500 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Cohort 2 TL011 1000 mg
n=3 Participants
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind TL011 1000 mg
n=25 Participants
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
n=23 Participants
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Total
n=54 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
52.56 Years
STANDARD_DEVIATION 13.4 • n=5 Participants
|
55.2 Years
STANDARD_DEVIATION 8.3 • n=7 Participants
|
56.8 Years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
56.7 Years
STANDARD_DEVIATION 12.2 • n=4 Participants
|
56.7 Years
STANDARD_DEVIATION 11.7 • n=21 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
45 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Race : White
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
53 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Race : Other
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 57Population: 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
Outcome measures
| Measure |
Double Blind TL011 1000 mg
n=21 Participants
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
n=18 Participants
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve [AUC(0-t)] in Part B
|
7571 Day*micrograms per milliliter
Standard Deviation 2219
|
8377 Day*micrograms per milliliter
Standard Deviation 2879
|
SECONDARY outcome
Timeframe: Day 1 to Day 57Population: 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
Outcome measures
| Measure |
Double Blind TL011 1000 mg
n=21 Participants
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
n=19 Participants
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|
|
Maximum Observed Concentration (Cmax) in Part B
|
396 Micrograms per milliliter
Standard Deviation 84.2
|
450 Micrograms per milliliter
Standard Deviation 109
|
SECONDARY outcome
Timeframe: From randomization up to Week 24Population: Safety analysis set included all participants who received at least one dose of study drug.
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.
Outcome measures
| Measure |
Double Blind TL011 1000 mg
n=25 Participants
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
n=23 Participants
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|
|
Number of Participants With Adverse Events in Part B
|
14 Participants
|
16 Participants
|
SECONDARY outcome
Timeframe: Day 1, Day 15Population: 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. Here, "number analyzed" signifies participants evaluable for this outcome measure. Numbers analyzed were not equal at each time point (C1max and C2max).
Outcome measures
| Measure |
Double Blind TL011 1000 mg
n=22 Participants
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
n=22 Participants
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|
|
Cmax Post First Dose (C1max) and Post Second Dose (C2max) in Part B
C1max
|
339 Micrograms per milliliter
Standard Deviation 68.2
|
356 Micrograms per milliliter
Standard Deviation 74.7
|
|
Cmax Post First Dose (C1max) and Post Second Dose (C2max) in Part B
C2max
|
348 Micrograms per milliliter
Standard Deviation 124
|
448 Micrograms per milliliter
Standard Deviation 110
|
SECONDARY outcome
Timeframe: Day 1, Day 15Population: 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. Here, "number analyzed" signifies participants evaluable for this outcome measure.
Outcome measures
| Measure |
Double Blind TL011 1000 mg
n=22 Participants
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
n=22 Participants
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|
|
AUC At First Dose (AUC1) and AUC At Second Dose (AUC2) in Part B
AUC1
|
2335 Day*micrograms per milliliter
Standard Deviation 527
|
2359 Day*micrograms per milliliter
Standard Deviation 634
|
|
AUC At First Dose (AUC1) and AUC At Second Dose (AUC2) in Part B
AUC2
|
6133 Day*micrograms per milliliter
Standard Deviation 2774
|
6849 Day*micrograms per milliliter
Standard Deviation 4532
|
SECONDARY outcome
Timeframe: Baseline to Day 57Population: PK population. Here, "number analyzed" signifies participants evaluable for this outcome measure.
Outcome measures
| Measure |
Double Blind TL011 1000 mg
n=20 Participants
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
n=18 Participants
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|
|
Percent Change From Baseline in CD19+ B-cell Count in Part B
|
-88.9 Percent change
Standard Deviation 25.9
|
-90.6 Percent change
Standard Deviation 23.1
|
SECONDARY outcome
Timeframe: Baseline to Day 57Population: Intent to Treat (ITT) population included all randomized participants regardless of the treatment actually received.
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 \[CRP\])
Outcome measures
| Measure |
Double Blind TL011 1000 mg
n=25 Participants
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
n=23 Participants
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|
|
Number of Participants With American College of Rheumatology (ACR20) Criteria Response in Part B
|
14 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: Day 1 to Day 57Population: Pharmacokinetics (PK) population included all participants that received at least one dose of 1000 mg TL011 and had sufficient plasma concentration results to allow estimation of PK parameters.
Data available for cohort 2 only per planned analysis.
Outcome measures
| Measure |
Double Blind TL011 1000 mg
n=3 Participants
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve [AUC (0-t)] for Part A Cohort 2
|
6423 Day*micrograms per milliliter
Standard Deviation 1956
|
—
|
SECONDARY outcome
Timeframe: From randomization up to Week 24Population: Safety analysis set included all participants who received at least one dose of study drug.
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.
Outcome measures
| Measure |
Double Blind TL011 1000 mg
n=3 Participants
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
n=3 Participants
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|
|
Number of Participants With Adverse Events in Part A
|
0 Participants
|
2 Participants
|
Adverse Events
Cohort 1 TL011 500 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort 2 TL011 1000 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Double Blind TL011 1000 mg
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Double Blind MabThera 1000 mg
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1 TL011 500 mg
n=3 participants at risk
Participants were administered 500 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Cohort 2 TL011 1000 mg
n=3 participants at risk
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind TL011 1000 mg
n=25 participants at risk
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
n=23 participants at risk
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
4.0%
1/25 • Number of events 1 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/23 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
Blood and lymphatic system disorders
Sideroblastic Anaemia
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/25 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
4.3%
1/23 • Number of events 1 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
Infections and infestations
Herpes Zoster
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/25 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
4.3%
1/23 • Number of events 1 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
Other adverse events
| Measure |
Cohort 1 TL011 500 mg
n=3 participants at risk
Participants were administered 500 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Cohort 2 TL011 1000 mg
n=3 participants at risk
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind TL011 1000 mg
n=25 participants at risk
Participants were administered 1000 mg of TL011, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
Double Blind MabThera 1000 mg
n=23 participants at risk
Participants were administered 1000 mg of MabThera, via intravenous (IV) infusion, two weeks apart (on Day 1 and on Day 15).
|
|---|---|---|---|---|
|
Cardiac disorders
Tachycardia
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
33.3%
1/3 • Number of events 1 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
4.0%
1/25 • Number of events 2 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
4.3%
1/23 • Number of events 1 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
General disorders
Fatigue
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
8.0%
2/25 • Number of events 2 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/23 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
General disorders
Pyrexia
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
8.0%
2/25 • Number of events 2 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/23 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
Injury, poisoning and procedural complications
Infusion Related Reaction
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
8.0%
2/25 • Number of events 3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/23 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
33.3%
1/3 • Number of events 1 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
4.0%
1/25 • Number of events 1 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
4.3%
1/23 • Number of events 1 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
33.3%
1/3 • Number of events 1 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
4.0%
1/25 • Number of events 1 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/23 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
8.0%
2/25 • Number of events 2 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
13.0%
3/23 • Number of events 3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
Infections and infestations
Rhinitis
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
8.0%
2/25 • Number of events 3 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/23 • Up to 24 weeks after first dose of study drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products R&D, Inc.
Phone: 1-888-483-8270
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
- Publication restrictions are in place
Restriction type: OTHER