Trial Outcomes & Findings for Study to Investigate the Safety and Efficacy of Tregalizumab in Subjects (MTX-IR) With Active Rheumatoid Arthritis (NCT NCT01999192)

Results Overview

The primary efficacy variable was the proportion of subjects with an ACR20 response after 12 weeks of double-blind treatment with the study medication. The analysis of the primary endpoint was performed using observed cases (OC) on the FAS.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

321 participants

Primary outcome timeframe

Week 12

Results posted on

2017-08-24

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Level 1 Tregalizumab 25mg Tregalizumab s.c. weekly	Dose Level 2 Tregalizumab 100mg Tregalizumab s.c. weekly	Dose Level 3 Tregalizumab 200mg Tregalizumab s.c. weekly	Placebo Placebo s.c. weekly
Main Phase I STARTED	83	80	78	80
Main Phase I COMPLETED	72	70	70	72
Main Phase I NOT COMPLETED	11	10	8	8
Main Phase II STARTED	64	75	98	44
Main Phase II COMPLETED	55	66	76	43
Main Phase II NOT COMPLETED	9	9	22	1
Extension Phase STARTED	54	56	68	0
Extension Phase COMPLETED	41	38	44	0
Extension Phase NOT COMPLETED	13	18	24	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Investigate the Safety and Efficacy of Tregalizumab in Subjects (MTX-IR) With Active Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1 Tregalizumab n=80 Participants 25mg Tregalizumab s.c. weekly	Dose Level 2 Tregalizumab n=78 Participants 100mg Tregalizumab s.c. weekly	Dose Level 3 Tregalizumab n=76 Participants 200mg Tregalizumab s.c. weekly	Placebo n=79 Participants Placebo s.c. weekly	Total n=313 Participants Total of all reporting groups
Age, Customized 0-<40 years	9 years n=5 Participants	19 years n=7 Participants	12 years n=5 Participants	10 years n=4 Participants	50 years n=21 Participants
Age, Customized 40-<=65 years	62 years n=5 Participants	56 years n=7 Participants	56 years n=5 Participants	57 years n=4 Participants	231 years n=21 Participants
Age, Customized >65 years	9 years n=5 Participants	3 years n=7 Participants	8 years n=5 Participants	12 years n=4 Participants	32 years n=21 Participants
Sex: Female, Male Female	71 Participants n=5 Participants	68 Participants n=7 Participants	58 Participants n=5 Participants	66 Participants n=4 Participants	263 Participants n=21 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants	13 Participants n=4 Participants	50 Participants n=21 Participants

PRIMARY outcome

Timeframe: Week 12

Population: The analysis of the primary endpoint was performed using observed cases (OC) on the FAS. Full analysis set (FAS): All subjects entered into the study who received at least one dose of study medication and have at least one post-baseline assessment.

The primary efficacy variable was the proportion of subjects with an ACR20 response after 12 weeks of double-blind treatment with the study medication. The analysis of the primary endpoint was performed using observed cases (OC) on the FAS.

Outcome measures

Outcome measures
Measure	Dose Level 1 Tregalizumab n=71 Participants 25mg Tregalizumab s.c. weekly	Dose Level 2 Tregalizumab n=66 Participants 100mg Tregalizumab s.c. weekly	Dose Level 3 Tregalizumab n=70 Participants 200mg Tregalizumab s.c. weekly	Placebo n=71 Participants Placebo s.c. weekly
The Proportion of Subjects Who Achieve an ACR20 at Week 12 Following Treatment With Tregalizumab + MTX Compared With Subjects Treated on Placebo + MTX	42.3 percentage of Subjects	47.0 percentage of Subjects	44.3 percentage of Subjects	35.2 percentage of Subjects

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 48 weeks

AUC, Cmax, Tmax at baseline, and at Week (W) 2/Visit (V) 4, W4/V5, W8/V7, W12/V8, W24/V10, W3/V122, W48 (end of Treatment \[EoT\]/ early termination ET), and at follow-up (post EoT/post ET).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 48 weeks

Outcome measures

Outcome data not reported

Adverse Events

25mg Dose Level 1 Tregalizumab

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

100mg Dose Level 2 Tregalizumab

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

200mg Dose Level 3 Tregalizumab

Serious events: 7 serious events

Other events: 15 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	25mg Dose Level 1 Tregalizumab n=105 participants at risk Dose Level 1 Tregalizumab (25mg)	100mg Dose Level 2 Tregalizumab n=117 participants at risk Dose Level 2 Tregalizumab (100mg)	200mg Dose Level 3 Tregalizumab n=122 participants at risk Dose Level 3 Tregalizumab (200mg)	Placebo n=80 participants at risk Placebo -
Infections and infestations Nasopharyngitis	6.7% 7/105 • Number of events 9 • through study completion, up to 1 year All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.	5.1% 6/117 • Number of events 7 • through study completion, up to 1 year All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.	5.7% 7/122 • Number of events 10 • through study completion, up to 1 year All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.	5.0% 4/80 • Number of events 4 • through study completion, up to 1 year All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.
Musculoskeletal and connective tissue disorders Rheumatoid Arthritis	4.8% 5/105 • Number of events 5 • through study completion, up to 1 year All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.	5.1% 6/117 • Number of events 6 • through study completion, up to 1 year All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.	4.1% 5/122 • Number of events 5 • through study completion, up to 1 year All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.	2.5% 2/80 • Number of events 3 • through study completion, up to 1 year All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.
Nervous system disorders Headache	2.9% 3/105 • Number of events 4 • through study completion, up to 1 year All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.	5.1% 6/117 • Number of events 9 • through study completion, up to 1 year All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.	4.9% 6/122 • Number of events 6 • through study completion, up to 1 year All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.	3.8% 3/80 • Number of events 3 • through study completion, up to 1 year All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.

Additional Information

Xuefei Zhou Manager Strategy & Development

Biotest AG

Phone: +496103801

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60