PHARMACEUTICAL COMBINATION COMPRISING AN ANTI-CD3 ANTIBODY AND A CXCR3 ANTAGONIST

1 . A pharmaceutical combination comprising a first active pharmaceutical ingredient which is 1-{(R)-2-(2-Hydroxy-ethyl)-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-(3-methyl-[1,2,4]triazol-1-yl)-ethanone, or a pharmaceutically acceptable salt thereof, and a second active pharmaceutical ingredient which is an anti-CD3 monoclonal antibody.

2 . A pharmaceutical combination according to claim 1 , wherein the first active pharmaceutical ingredient is 1-{(R)-2-(2-Hydroxy-ethyl)-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-(3-methyl-[1,2,4]triazol-1-yl)-ethanone.

3 . A pharmaceutical combination according to claim 1 , wherein the second active pharmaceutical ingredient is a humanized or fully human anti-CD3 monoclonal antibody.

4 . A pharmaceutical combination according to claim 1 , wherein the second active pharmaceutical ingredient is teplizumab.

5 . A pharmaceutical combination according to claim 1 , wherein 1-{(R)-2-(2-Hydroxy-ethyl)-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-(3-methyl-[1,2,4]triazol-1-yl)-ethanone, or a pharmaceutically acceptable salt thereof, is comprised in a pharmaceutical dosage form for oral or intravenous administration of 1-{(R)-2-(2-Hydroxy-ethyl)-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-(3-methyl-[1,2,4]triazol-1-yl)-ethanone, or of a pharmaceutically acceptable salt thereof.

6 . A pharmaceutical combination according to claim 5 , wherein 1 -{(R)- 2 -( 2 -Hydroxy-ethyl)- 4 -[ 2 -trifluoromethyl- 4 -( 2 -trifluoromethyl-pyrimidin- 5 -yl)-thiazol- 5 -yl]-piperazin- 1 -yl}- 2 -( 3 -methyl-[ 1 , 2 , 4 ]triazol- 1 -yl)-ethanone is comprised in the pharmaceutical dosage form in a unit dose between 4 . 0 mg and 100 mg.

7 . A pharmaceutical combination according to claim 1 , wherein the anti-CD3 monoclonal antibody is comprised in a pharmaceutical dosage form for intravenous administration of the anti-CD3 monoclonal antibody.

8 . A pharmaceutical combination according to claim 7 , wherein the anti-CD3 monoclonal antibody is comprised in the pharmaceutical dosage form in a unit dose between 50 μg/m 2 BSA and 1000 μg/m 2 BSA.

9 . A pharmaceutical combination according to claim 1 , wherein the first and the second active pharmaceutical ingredient are comprised in separated pharmaceutical compositions.

10 . (canceled)

11 . A method for the prevention/prophylaxis and/or treatment of a disease or disorder selected from type 1 diabetes, multiple sclerosis, organ transplant rejection, thyroid eye disease, rheumatoid arthritis, ulcerative colitis, crohn's disease, celiac disease, atherosclerosis, psoriasis, lung inflammation, and psoriatic arthritis in a patient in need thereof, wherein the method comprises administering to the patient an effective amount of 1-{(R)-2-(2-Hydroxy-ethyl)-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-(3-methyl-[1,2,4]triazol-1-yl)-ethanone, or a pharmaceutically acceptable salt thereof. and an effective amount of an anti-CD3 monoclonal antibody.

12 . A method for the prevention/prophylaxis and/or treatment of type 1 diabetes in a patient in need thereof, wherein the method comprises administering to the patient an effective amount of 1-{(R)-2-(2-Hydroxy-ethyl)-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-(3-methyl-[1,2.4]triazol-1-yl)-ethanone, or a pharmaceutically acceptable salt thereof. and an effective amount of an anti-CD3 monoclonal antibody.

13 . A method according to claim 11 , wherein 1-{(R)-2-(2-Hydroxy-ethyl)-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-(3-methyl-[1,2,4]triazol-1-yl)-ethanone, or a pharmaceutically acceptable salt thereof, is administered to the patient once or twice per day.

14 . A method according to claim 11 , wherein the anti-CD3 monoclonal antibody is administered to the patient for a treatment period of 2 to 30 days.

15 . A method according to claim 14 , wherein the cumulative dose of the anti-CD3 monoclonal antibody administered to the patient is between 5.0 mg and 40 mg.

16 . A method according to claim 12 , wherein progression from Stage 2 type 1 diabetes to Stage 3 type 1 diabetes is delayed by at least 24 months in at least 75% of the patients compared to untreated patients.

17 . A pharmaceutical composition comprising as active principle 1-{(R)-2-(2-Hydroxy-ethyl)-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-(3-methyl-[1,2,4]triazol-1-yl)-ethanone, or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient, wherein the pharmaceutical composition-is to be administered and/or is administered in combination with a second pharmaceutical composition comprising, as active principle, an anti-CD3 monoclonal antibody and at least one therapeutically inert excipient.

18 . A method according to claim 12 , wherein 1-{(R)-2-(2-Hydroxy-ethyl)-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-2-(3-methyl-[1,2,4]triazol-1-yl)-ethanone, or a pharmaceutically acceptable salt thereof, is administered to the patient once or twice per day.

19 . A method according to claim 12 , wherein the anti-CD3 monoclonal antibody is administered to the patient for a treatment period of 2 to 30 days.

20 . A method according to claim 19 , wherein the cumulative dose of the anti-CD3 monoclonal antibody administered to the patient is between 5.0 mg and 40 mg.

21 . A method according to claim 12 , wherein the anti-CD3 monoclonal antibody is teplizumab.