Study of a Monoclonal Antibody KHK4083 in Moderate Ulcera... | NCT02647866

NCT02647866

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
KHK4083 Cohort 1	Experimental	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.	Drug: KHK4083
KHK4083 Cohort 2	Experimental	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.	Drug: KHK4083
KHK4083 Cohort 3	Experimental	Subjects received one 10.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.	Drug: KHK4083
KHK4083 Cohort 4	Experimental	Subjects received one maximum tolerated dose (10.0 mg/kg) IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.

Name	Type	Description	Arm Group Labels	Other Names
KHK4083	Drug	IV Infusion	KHK4083 Cohort 1 KHK4083 Cohort 2 KHK4083 Cohort 3 KHK4083 Cohort 4

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Subjects With Treatment-related Adverse Events	To determine the safety and tolerability of KHK4083	Up to 52 weeks
Number of Subjects With Treatment-related Serious Adverse Events	To determine the safety and tolerability of KHK4083	Up to 52 weeks
Number of Subjects Who Show Improvement in the Mucosa at Week 12	Measured by the modified Mayo endoscopy sub-score (mMES), which ranges from 0-3 with higher scores = more severe disease.	12 weeks
Proportion of Subjects Who Show Improvement in the Mucosa at Week 52	Measured by the modified Mayo endoscopy sub-score (mMES), which ranges from 0-3 with higher scores = more severe disease.	52 weeks

Secondary Outcomes

Measure	Description	Time Frame
Number of Subjects With Confirmed Anti-KHK4083 Antibodies (Immunogenicity)	The immunogenicity was assessed by determination of the development of anti-drug antibodies (ADA) against KHK4083.	52 weeks
Number of Subjects Who Achieve Mucosal Healing at Week 12

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject is able and willing to comply with study procedures, and to adhere to dosing, visit schedules and follow-up procedures as described in the protocol and ICF;
Subject voluntarily signs/dates an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF in accordance with regulatory and Institutional Guidelines;
Male and female subjects ≥ 18 years of age at the time of enrollment;
Subject has UC that was diagnosed at least 6 months prior to the Screening visit;
Subject has moderately active UC with a total Mayo score of 4-9 and an endoscopic sub-score of at least 2, with disease that extends at least 15 cm from the anal verge;
Subject has had previous treatment (within 5 years prior to Screening) with one or more of the following: corticosteroids, immunosuppressive medications or TNF antagonist therapy that was unsuccessful because of a lack of efficacy response.
Female subjects (WOCBP) must have a negative pregnancy test at Screening and Baseline. WOCBP must agree to use effective contraception;
Male subjects (including those who have had a vasectomy) must use adequate contraception during the study and for at least 6 months after the last dose of investigational product.

Exclusion Criteria:

Subject, who, for any reason, is judged by the Investigator to be inappropriate for this study;
Subject has a medical history of other clinically significant diseases/disorders;
Two or more biologic treatments with different mechanisms of action (e.g., infliximab, vedolizumab and golimumab) or Three or more anti-TNF biologics e.g. infliximab, adalimumab
Subject requires prescription treatment for UC, except for the stable, oral treatment of UC for 4 weeks prior to screening.
Subject has received any of the following prior treatments or treatments within the specified time prior to the Baseline visit:
- Natalizumab, efalizumab, rituximab or other lymphocyte-depleting treatments, including but not limited, to alkylating agents (such as cyclophosphamide or chlorambucil) and total lymphoid irradiation at any time;
- TNF antagonists within 8 weeks, or 5 half-lives (up to 12 weeks);
- Vedolizumab within 16 weeks;
- Methotrexate, cyclosporine, mycophenolate, tacrolimus, thalidomide, or other immune altering drugs within 4 weeks (ophthalmologic preparations are permitted);
- 5-ASA enema, steroid enema or suppository use within 2 weeks ; and/or Investigational agents within 8 weeks or 5 half-lives (whichever is longer).
Subject with recent, suspected or confirmed symptomatic stenosis of the colon, abdominal abscess, or ischemic colitis based on clinical or radiographic data; a history of toxic megacolon; or who had any previous surgery for UC;
Subject with known colonic dysplasia, adenomas or polyposis;
Subject had major surgery within 4 weeks prior to Screening or an anticipated requirement for major surgery;
Subject with enteric pathogens (including Clostridium difficile);
Subject with any of the following hematological and chemistry laboratory values:
- Platelet count < 100,000/mm3;
- Neutrophils < 1500/mm3;
- Serum creatinine ≥ 1.6 mg/dL (≥ 144.4 μmol/L);
- Alkaline phosphatase > 3 times the upper limit of normal (ULN);
- AST or ALT > 2 times ULN;
- Total bilirubin > 2 mg/dL, unless due to Gilbert's Syndrome;
- Serum albumin < 3 g/dL;
- Hemoglobin < 9 g/dL;
- Glycated serum hemoglobin A1c ≥ 9%.
Subject has clinically significant cardiac disease;
Subject is pregnant or breastfeeding;
Subject has had major immunologic reaction;
Subject is Hepatitis B core antibody or surface antigen positive and/or Hepatitis C antibody positive with detectable RNA;
Subject has a history of human immunodeficiency virus (HIV) positivity, tests positive for HIV, or has congenital or acquired immunodeficiency;
Subject has or has had active TB, suspected extra-pulmonary TB, a history of incompletely treated TB, or latent TB or other latent infection. Subjects with latent TB (clinical findings, purified protein derivative [PPD] or interferon gamma release assay [IGRA]) may be included in the study if prophylactic therapy for latent TB is started at least 4 weeks prior to Screening. Subjects with a potentially untreated other infection (clinical findings) are to be excluded.
Subject has bacterial infections requiring treatment with oral or parenteral antibiotics, within 2 and 4 weeks, respectively.
Subject has a history of systemic opportunistic infection or recurrent infections
Subject has malignancy or history of malignancy, except for adequately treated basal cell skin cancer or adequately treated carcinoma in-situ of the cervix without recurrence at least 5 years.
Subject who received a bacille Calmette-Guérin (BCG) vaccine within 6 months of randomization or live vaccination (e.g., measles, mumps, rubella [MMR]; herpes zoster; varicella, intranasal influenza; and oral poliomyelitis) within 4 weeks of randomization.
Subject with a history of or active substance abuse.
Subject has other severe acute or chronic medical or psychiatric condition or laboratory abnormality.

Contacts/Locations Module

Name	Affiliation	Role
Vincent Strout, MBA	Kyowa Kirin, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Greenville	South Carolina	29615	United States

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 4, 2016	Aug 12, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
BG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
BG002	KHK4083 Cohort 3	Subjects received one 10.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
BG003	KHK4083 Cohort 4	Subjects received one maximum tolerated dose (10.0 mg/kg) IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
BG004	Placebo	Subjects received one IV infusion treatment of Placebo every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48. Subjects who participated in Open-Label Therapy received KHK4083 instead of placebo.
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020 BG003

Age, Continuous

Mean

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00047.3(18 to 67) BG00146.1(21 to 75) BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0004 BG0012 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Subjects With Treatment-related Adverse Events

To determine the safety and tolerability of KHK4083

Safety Analysis Set - All randomized subjects who received any (even partial dose) investigational product (KHK4083 or placebo).

Posted

Count of Participants

Participants

Up to 52 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG002	KHK4083 Cohort 3	Subjects received one 10.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG003	KHK4083 Cohort 4	Subjects received one maximum tolerated dose (10.0 mg/kg) IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG004	KHK4083 Combined	The total number of participants analyzed who were randomized to KHK4083 during Induction Therapy.
OG005	Placebo	Subjects received placebo IV infusion treatments from Baseline to Week 12. Subjects who completed double-blind Induction Therapy (i.e., at least five of six treatments) were eligible to enter OLE Therapy and receive 10 treatments of open-label KHK4083 (at the same dose administered to that subject during Induction Therapy) as maintenance therapy. Each subject was to receive one IV infusion every 4 weeks from Week 12 to Week 48.

Units	Counts
Participants	OG0009 OG00110 OG0029 OG003

Title

Denominators

Categories

With Any TEAE

Title	Measurements
	OG0005 OG0017 OG0027 OG003

Primary

Number of Subjects With Treatment-related Serious Adverse Events

To determine the safety and tolerability of KHK4083

Safety Analysis Set - All randomized subjects who received any (even partial dose) investigational product (KHK4083 or placebo).

Posted

Count of Participants

Participants

Up to 52 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG002	KHK4083 Cohort 3	Subjects received one 10.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.

Primary

Number of Subjects Who Show Improvement in the Mucosa at Week 12

Measured by the modified Mayo endoscopy sub-score (mMES), which ranges from 0-3 with higher scores = more severe disease.

Full analysis set - All randomized subjects who received at least one full dose of investigational product and had a Baseline and at least one post-treatment primary efficacy variable.

Posted

Count of Participants

Participants

12 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG002	KHK4083 Cohorts 3 + 4 Combined	Subjects received one 10.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.

Primary

Proportion of Subjects Who Show Improvement in the Mucosa at Week 52

Measured by the modified Mayo endoscopy sub-score (mMES), which ranges from 0-3 with higher scores = more severe disease.

Posted

Count of Participants

Participants

52 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG002	KHK4083 Cohorts 3 + 4 Combined	Subjects received one 10.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.

Secondary

Number of Subjects With Confirmed Anti-KHK4083 Antibodies (Immunogenicity)

The immunogenicity was assessed by determination of the development of anti-drug antibodies (ADA) against KHK4083.

All subjects who received at least one dose of KHK4083, including 14 subjects initially randomized to placebo and who then continued into Open-Label Extension therapy, where they received the maximum tolerated dose of KHK4083.

Posted

Count of Participants

Participants

52 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG002	KHK4083 Cohort 3	Subjects received one 10.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.

Secondary

Number of Subjects Who Achieve Mucosal Healing at Week 12

The endoscopic Mayo Score (Mayo endoscopic subscore) evaluates ulcerative colitis stage, based only on endoscopic exploration. The scale ranges from 0 to 3, with higher scores = more severe activity. Mucosal healing is defined as modified Mayo endoscopy sub-score (mMES) of 0 or 1 at Week 12.

Full analysis set - All randomized subjects who received at least one full dose of investigational product and had a Baseline and at least one post-treatment primary efficacy variable.

Posted

Count of Participants

Participants

12 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG002	KHK4083 Cohorts 3 + 4 Combined

Secondary

Number of Subjects Who Achieve Mucosal Healing at Week 52

Posted

Count of Participants

Participants

52 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG002	KHK4083 Cohorts 3 + 4 Combined	Subjects received one 10.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.

Secondary

Number of Subjects Who Achieve Clinical Improvement at Week 12

Full analysis set - All randomized subjects who received at least one full dose of investigational product and had a Baseline and at least one post-treatment primary efficacy variable.

Posted

Count of Participants

Participants

12 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG002

Secondary

Change From Baseline in Total Mayo Scale Score at Week 52

The overall number of participants is the number in the full analysis set. The number of patients analyzed is the number of patients who had values at the noted visits.

There were no subjects in the 10.0 mg/kg KHK4083 group in the LTE Therapy Period. There were no subjects in the 1.0 mg/kg KHK4083 group in the OLE Therapy Period.

Posted

Mean

Standard Deviation

score on a scale

52 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.

Secondary

Number of Subjects Who Achieve a Clinical Response at Week 12

Full analysis set - All randomized subjects who received at least one full dose of investigational product and had a Baseline and at least one post-treatment primary efficacy variable.

Posted

Count of Participants

Participants

12 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG002

Secondary

Number of Subjects Who Achieve a Clinical Response at Week 52

The Mayo Clinic Score is comprised of 4 parts: stool frequency, rectal bleeding, endoscopic findings and physician's global assessment, each scored from 0-3. The total score ranges from 0-12 with higher scores indicating increased severity of disease. Clinical Response indicates the change from Baseline in the Total Mayo Clinic score <= -3 and the percentage change from Baseline in the Total Mayo Clinic score <= -30% to Week 12, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of <= 1.

Posted

Count of Participants

Participants

52 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG002

Secondary

Number of Subjects Who Achieve Clinical Remission at Week 12

Posted

Count of Participants

Participants

12 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG002	KHK4083 Cohorts 3 + 4 Combined	Subjects received one 10.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.

Secondary

Number of Subjects Who Achieve Clinical Remission at Week 52

Posted

Count of Participants

Participants

52 weeks

ID	Title	Description
OG000	KHK4083 Cohort 1	Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG001	KHK4083 Cohort 2	Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
OG002	KHK4083 Cohorts 3 + 4 Combined	Subjects received one 10.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	KHK4083 Cohort 1	Subjects who qualify will receive 1.0 mg/kg IV infusion treatments of KHK4083 from Baseline to Week 48.	0	9	1	9	5	9
EG001	KHK4083 Cohort 2	Subjects who qualify will receive 3.0 mg/kg IV infusion treatments of KHK4083 from Baseline to Week 48.	1	10	1	10	7	10
EG002	KHK4083 Cohort 3	Subjects who qualify will receive 10.0 mg/kg IV infusion treatments of KHK4083 from Baseline to Week 48.	0	9	1	9	7	9
EG003	KHK4083 Cohort 4	Subjects who qualify will receive maximum tolerated dose (10.0 mg/kg) IV infusion treatments of KHK4083 from Baseline to Week 48.	0	21	3	21	13	21
EG004	KHK4083 Combined	The total number of participants analyzed who were randomized to KHK4083 during Treatment parts A & B.	1	49	6	49	32	49
EG005	Placebo	Subjects received placebo IV infusion treatments from Baseline to Week 12. Subjects who completed double-blind Induction Therapy (i.e., at least five of six treatments) were eligible to enter OLE Therapy and receive 10 treatments of open-label KHK4083 (at the same dose administered to that subject during Induction Therapy) as maintenance therapy. Each subject was to receive one IV infusion every 4 weeks from Week 12 to Week 48.	0	17	3	17	13	17

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG0030 events0 affected21 at risk EG0040 events0 affected49 at risk EG0052 events1 affected17 at risk
Myocardial infarction	Cardiac disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0012 events1 affected10 at risk EG0020 events0 affected9 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0001 events1 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Colitis ulcerative	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0002 events1 affected9 at risk EG0010 events0 affected10 at risk EG0021 events1 affected9 at risk EG003
Hepatotoxicity	Hepatobiliary disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Pneumonia	Infections and infestations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Post procedural infection	Infections and infestations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Blood albumin decreased	Investigations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Abscess drainage	Surgical and medical procedures	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (18.1)	Systematic Assessment	EG0002 events2 affected9 at risk EG0012 events2 affected10 at risk EG0020 events0 affected9 at risk EG0033 events3 affected21 at risk EG0047 events7 affected49 at risk EG0054 events3 affected17 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0021 events1 affected9 at risk EG003
Thrombocytosis	Blood and lymphatic system disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0021 events1 affected9 at risk EG003
Sinus bradycardia	Cardiac disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0021 events1 affected9 at risk EG003
Renal aplasia	Congenital, familial and genetic disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected10 at risk EG0020 events0 affected9 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0013 events3 affected10 at risk EG0020 events0 affected9 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected10 at risk EG0020 events0 affected9 at risk EG003
Abdominal tenderness	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Colitis ulcerative	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0001 events1 affected9 at risk EG0011 events1 affected10 at risk EG0021 events1 affected9 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0012 events1 affected10 at risk EG0020 events0 affected9 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected10 at risk EG0020 events0 affected9 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0001 events1 affected9 at risk EG0010 events0 affected10 at risk EG0021 events1 affected9 at risk EG003
Mucous stools	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected10 at risk EG0020 events0 affected9 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected10 at risk EG0020 events0 affected9 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Asthenia	General disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0021 events1 affected9 at risk EG003
Chest discomfort	General disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0021 events1 affected9 at risk EG003
Chills	General disorders	MedDRA (18.1)	Systematic Assessment	EG0001 events1 affected9 at risk EG0011 events1 affected10 at risk EG0020 events0 affected9 at risk EG003
Pyrexia	General disorders	MedDRA (18.1)	Systematic Assessment	EG0003 events3 affected9 at risk EG0011 events1 affected10 at risk EG0021 events1 affected9 at risk EG003
Hepatic steatosis	Hepatobiliary disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Influenza	Infections and infestations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Oral herpes	Infections and infestations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Pharyngitis	Infections and infestations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Sinusitis	Infections and infestations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected10 at risk EG0020 events0 affected9 at risk EG003
Tonsillitis	Infections and infestations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Scar	Injury, poisoning and procedural complications	MedDRA (18.1)	Systematic Assessment	EG0001 events1 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Amylase increased	Investigations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Aspartate aminotransferase abnormal	Investigations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Blood creatine phosphokinase abnormal	Investigations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0021 events1 affected9 at risk EG003
Blood folate decreased	Investigations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0021 events1 affected9 at risk EG003
C-reactive protein increased	Investigations	MedDRA (18.1)	Systematic Assessment	EG0001 events1 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Lipase increased	Investigations	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.1)	Systematic Assessment	EG0002 events2 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0021 events1 affected9 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (18.1)	Systematic Assessment	EG0001 events1 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Headache	Nervous system disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected10 at risk EG0021 events1 affected9 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected10 at risk EG0020 events0 affected9 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected10 at risk EG0020 events0 affected9 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0010 events0 affected10 at risk EG0021 events1 affected9 at risk EG003
Oropharyageal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Systematic Assessment	EG0001 events1 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Systematic Assessment	EG0000 events0 affected9 at risk EG0011 events1 affected10 at risk EG0020 events0 affected9 at risk EG003
Pruritis	Skin and subcutaneous tissue disorders	MedDRA (18.1)	Systematic Assessment	EG0001 events1 affected9 at risk EG0010 events0 affected10 at risk EG0020 events0 affected9 at risk EG003

ID	Term
D003093	Colitis, Ulcerative
D004066	Digestive System Diseases
D003092	Colitis
D005767	Gastrointestinal Diseases
D015212	Inflammatory Bowel Diseases
D007410	Intestinal Diseases
D003108	Colonic Diseases
D001327	Autoimmune Diseases
D015746	Abdominal Pain

Ancestor Terms

ID	Term
D005759	Gastroenteritis
D007154	Immune System Diseases
D010146	Pain
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D012817	Signs and Symptoms, Digestive

ID	Term
C000627613	KHK4083

EG0042 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0044 events3 affected49 at risk

EG0050 events0 affected17 at risk

EG0040 events0 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0051 events1 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0042 events2 affected49 at risk

EG0051 events1 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0040 events0 affected49 at risk

EG0050 events0 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0040 events0 affected49 at risk

EG0050 events0 affected17 at risk

EG0043 events3 affected49 at risk

EG0051 events1 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0045 events5 affected49 at risk

EG0055 events5 affected17 at risk

EG0042 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0042 events2 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0051 events1 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0043 events3 affected49 at risk

EG0050 events0 affected17 at risk

EG0046 events6 affected49 at risk

EG0050 events0 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0041 events1 affected49 at risk

EG0051 events1 affected17 at risk

EG0042 events2 affected49 at risk

EG0050 events0 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0041 events1 affected49 at risk

EG0051 events1 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0040 events0 affected49 at risk

EG0052 events2 affected17 at risk

EG0040 events0 affected49 at risk

EG0052 events2 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0043 events2 affected49 at risk

EG0051 events1 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0043 events3 affected49 at risk

EG0051 events1 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0040 events0 affected49 at risk

EG0051 events1 affected17 at risk

EG0041 events1 affected49 at risk

EG0051 events1 affected17 at risk

EG0042 events2 affected49 at risk

EG0051 events1 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk

EG0041 events1 affected49 at risk

EG0050 events0 affected17 at risk