A Dose-Finding Study of Vedolizumab for Treatment of Steroid-Refractory Acute Intestinal Graft-Versus-Host Disease (GvHD) in Participants Who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Time frame: From first dose up to Day 28

Population: SAS included all participants who received any amount of the study drug.

CR is defined as the resolution of all signs and symptoms of acute graft-versus-host-disease (GvHD). VGPR is defined as resolution of the signs and symptoms of the GvHD: 1) Skin: no rash, or residual erythematous rash involving \<25% of the body surface, without bullae (excluding residual faint erythema and hyperpigmentation). 2) Liver: total serum bilirubin concentration \<2 mg/dL or \<25% of baseline at enrollment. 3) Gut: a) participant tolerates food or enteral feeding; b) predominantly formed stools; c) no overt gastrointestinal bleeding or abdominal cramping; d) no more than occasional nausea or vomiting. PR is defined as improvement of 1 GvHD stage in 1 or more organs without progression in any organ.

Time frame: Day 28

Population: Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.

Time frame: Day 99 (pre-dose)

Population: Pharmacokinetic (PK) set included all participants from the safety set with at least 1 post dose PK sample collected.

The Kaplan-Meier estimate reports the percentage of participants surviving at Months 6 and 12.

Time frame: Months 6 and 12

Population: Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Time frame: From first dose of study drug to 18 weeks after last dose (Up to Week 32)

Population: SAS included all participants who received any amount of the study drug.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

Time frame: From first dose of study drug to 18 weeks after last dose (Up to Week 32)

Population: SAS included all participants who received any amount of the study drug.

Clinical Laboratory parameters included tests for chemistry, hematology and urinalysis. Markedly abnormal values during treatment period were categorized as:alanine aminotransferase (ALT)\>3.0 U/L\*upper limit of normal(ULN),albumin\<25 g/L\*lower limit of normal(LLN),alkaline phosphatase \>3.0 U/L\*ULN,aspartate aminotransferase \>3.0 U/L\*ULN,bilirubin \>2 umol/L\*ULN,blood urea nitrogen(BUN) \>10.7 mmol/L,calcium \<1.75 mmol/L, \>2.88 mmol/L,chloride \<75 mmol/L, \>126 mmol/L,creatinine \>177umol/L,gamma glutamyl transferase (GGT) \>3 U/L\*ULN,glucose \<2.8 mmol/L, \>19.4 mmol/L,phosphate \<0.52 mmol/L, \>2.10 mmol/L,potassium\<3 mmol/L, \>6 mmol/L,sodium \<130 mmol/L, \>150 mmol/L,basophils \>3(10\^9/L)\*ULN,eosinophils \>2(10\^9/L)\*ULN,hematocrit (%) \<0.8\*LLN, \>1.2\*ULN,hemoglobin \<0.8 g/L\*LLN, \>1.2 g/L\*ULN,leukocytes \<0.5 (10\^9/L)\*LLN, \>1.5 (10\^9/L)\*ULN,lymphocytes \<0.5 (10\^9/L)\*LLN, \>1.5(10\^9/L)\*ULN,monocytes \>2 (10\^9/L)\*ULN,neutrophils \<0.5(10\^9/L)\*LLN, \>1.5 (10\^9/L)\*ULN,platelets \<75(10\^9/L), \>600(10\^9/L).

Time frame: From Baseline up to last dose of study drug (Day 99)

Population: SAS included all participants who received any amount of the study drug.

Vital signs included heart rate, respiratory rate, systolic and diastolic blood pressure, temperature and weight. The vital sign values outside the range: systolic blood pressure (SBP) \<85 mmHg and change from Baseline (BL) \<=-20 mmHg, \>180 mmHg and change from Baseline \>=20 mmHg,diastolic blood pressure (DBP) \<50 mmHg and change from Baseline \<=-15 mmHg, \>110 mmHg and change from Baseline \>=15 mmHg, heart rate \<50 beats per minute (bpm),\>120 beats per minute, temperature \<35.6 Degree C, \>37.7 Degree C and weight change from Baseline \<=-7 % and weight change from Baseline \>=7 % assessed during treatment period were considered markedly abnormal.

Time frame: From Baseline up to last dose of study drug (Day 99)

Population: SAS included all participants who received any amount of the study drug.

Time frame: Months 6 and 12

Population: Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.

Time frame: Month 6

Population: Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.

CR is defined as the resolution of all signs and symptoms of acute GvHD.

Time frame: Day 28

Population: Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.

Symptoms of acute intestinal GvHD were measured using the BMT CTN-modified International Bone Marrow Transplant Registry Database (IBMTR) index. Intestinal overall response is either CR, VGPR or PR for intestine only. CR is defined as the resolution of all signs and symptoms of GvHD. VGPR is defined as resolution of the majority of signs and symptoms of intestinal GvHD: a) participant tolerates food or enteral feeding; b) predominantly formed stools; c) no overt gastrointestinal bleeding or abdominal cramping; d) no more than occasional nausea or vomiting. PR is defined as improvement of intestinal GvHD by at least 1 stage.

Time frame: Day 28

Population: Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.

Total Steroids administered in mg/kg/day of methylprednisolone or equivalent

Time frame: From first dose of study drug up to Months 6 and 12

Population: Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.