Clinical Trials Register

Summary
EudraCT Number:	2017-000573-37
Sponsor's Protocol Code Number:	SHP647-303
National Competent Authority:	Ireland - HPRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-09-04
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Ireland - HPRA

A.2

EudraCT number

2017-000573-37

A.3

Full title of the trial

A Phase 3 Randomized, Double-blind, Placebo controlled, Parallel group Efficacy and Safety Study of SHP647 as Maintenance Therapy in Subjects With Moderate to Severe Ulcerative Colitis (FIGARO UC 303)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Research study to determine whether an investigational drug, SHP647, is safe and effective in the treatment of moderate to severe Ulcerative Colitis, compared with placebo (dummy treatment) – using a randomised and blinded study design (investigator and patients are not aware whether they receive study drug or placebo)(FIGARO UC 303).

A.3.2

Name or abbreviated title of the trial where available

FIGARO UC 303

A.4.1

Sponsor's protocol code number

SHP647-303

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03290781

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Shire Human Genetic Therapies, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Shire Human Genetic Therapies, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Shire Human Genetic Therapies, Inc.
B.5.2	Functional name of contact point	Holly Oakley
B.5.3	Address:
B.5.3.1	Street Address	300 Shire Way
B.5.3.2	Town/ city	Lexington
B.5.3.3	Post code	MA 02421
B.5.3.4	Country	United States
B.5.4	Telephone number	0017818967560
B.5.6	E-mail	holly.oakley@takeda.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	SHP647
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ontamalimab
D.3.9.2	Current sponsor code	SHP647
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	SHP647
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ontamalimab
D.3.9.2	Current sponsor code	SHP647
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ulcerative colitis

E.1.1.1

Medical condition in easily understood language

Long-term condition that results in inflammation and ulcers of the colon and rectum

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045365
E.1.2	Term	Ulcerative colitis
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to evaluate the efficacy of ontamalimab as maintenance treatment of remission, based on composite score of patient reported symptoms and centrally read endoscopy, in subjects with moderate to severe UC.

E.2.2

Secondary objectives of the trial

The key secondary objectives of the study are as follows:
• To evaluate the efficacy of ontamalimab on endoscopic remission, based on centrally read endoscopy.
• To evaluate the efficacy of ontamalimab on clinical remission, based on composite score of patient-reported symptoms.
• To evaluate the efficacy of ontamalimab on maintenance of remission among subjects in remission at baseline of the SHP647-303 study, based on composite score of patient-reported symptoms and centrally read endoscopy.
• To evaluate the efficacy of ontamalimab on clinical response, based on composite score of patient-reported symptoms and centrally read endoscopy.
• To evaluate the efficacy of ontamalimab on mucosal healing, based on a centrally read endoscopic and histological assessment using the Geboes Score grading system.
• To evaluate the efficacy of ontamalimab on glucocorticoid free clinical remission.
• To evaluate the efficacy of ontamalimab on glucocorticoid free remission.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study.
1. Subjects and/or their parent or legally authorized representative must have an understanding, ability, and willingness to fully comply with study procedures and restrictions.
2. Subjects must be able to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent and/or assent, as applicable, to participate in the study.
3. Subjects must have completed the 12 week induction treatment period from study SHP647 301 or SHP647-302.
4. Subjects must have achieved clinical response in induction study SHP647-301 or SHP647 302. Clinical response is defined as:
1) A decrease from the induction study (SHP647 301 or SHP647-302) baseline in the composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding ≥1 point or a subscore for rectal bleeding ≤1
OR
2) A decrease from the induction study (SHP647 301 or SHP647-302) baseline in total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.
For eligibility assessment, clinical response will be determined based on the centrally read endoscopy performed during screening and at Week 12 of induction study SHP647 301 or SHP647 302.
5. Subjects receiving any treatment(s) for UC described in Section 5.2.1 are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.

E.4

Principal exclusion criteria

Subjects are excluded from the study if any of the following exclusion criteria are met:
1. Subjects who had major protocol deviation(s) (as determined by the sponsor) in induction study SHP647 301 or SHP647 302.
2. Subjects who permanently discontinued investigational product because of an adverse event (AE), regardless of relatedness to investigational product, in induction study SHP647-301 or SHP647-302.
3. Subjects who are likely to require surgery for UC during the study period.
4. Subjects are females who became pregnant during induction study SHP647-301 or SHP647 302, females who are planning to become pregnant during the study period, or males or females of childbearing potential not agreeing to continue appropriate contraception methods (ie, highly
effective methods for female and medically appropriate methods for male study subjects)through the conclusion of study participation.
5. Subjects who do not agree to postpone donation of any organ or tissue, including male subjects who are planning to bank or donate sperm and female subjects who are planning
to harvest or donate eggs for the duration of the study and through 16 weeks after last dose of investigational product.
6. Subjects who, in the opinion of the investigator or the sponsor, will be uncooperative or unable to comply with study procedures.
7. Subjects who have a newly diagnosed malignancy or recurrence of malignancy (other than resected cutaneous basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the uterine cervix that has been treated with no evidence of recurrence).
8. Subjects who have developed any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal (except disease under study), endocrine, cardiovascular, pulmonary, immunologic [eg, Felty’s syndrome], or local active infection/infectious illness) that, in the investigator’s judgment, will substantially increase the risk to the subject if he or she participates in the study.
9. Subjects with any other severe acute or chronic medical or psychiatric condition or laboratory or ECG abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
10. Subjects with known exposure to Mycobacterium tuberculosis (TB) since testing at screening in induction study SHP647-301 or SHP647-302 and who are without a generally accepted course of treatment.
11. Subjects who are investigational site staff members or relatives of those site staff members or subjects who are sponsor employees directly involved in the conduct of the study.
12. Subjects who are participating in or plan to participate in other investigational studies (other than induction study SHP647-301 or SHP647 302) during study SHP647-303.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is proportion of subjects in remission at the Week 52 visit. Remission is defined as a composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy as follows:
• stool frequency subscore of 0 or 1 with at least a 1-point change from induction (SHP647 301 or SHP647 302) baseline
AND
• rectal bleeding subscore of 0
AND
• endoscopic subscore of 0 or 1 (modified, excludes friability).

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 52 visit

E.5.2

Secondary end point(s)

The key secondary efficacy endpoints are as follows:
• Endoscopic remission, as defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability), at the Week 52 visit.
• Clinical remission as defined by stool frequency subscore of 0 or 1 with at least a 1-point change from induction study (SHP647-301 or SHP647-302) baseline in stool frequency subscore, and rectal bleeding subscore of 0, at the Week 52 visit.
• Sustained remission, ie, in remission at the SHP647-303 Week 52 visit, among subjects who were in remission at the time of baseline in study SHP647 303. Remission is defined as a composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy, with stool frequency subscore of 0 or 1 with at least a 1-point change from induction study (SHP647-301 or SHP647-302) baseline, and rectal bleeding subscore of 0, and endoscopic subscore of 0 or 1 (modified, excludes friability).
• Clinical response based on composite score at the Week 52 visit. Clinical response (composite) is defined as a decrease from induction study (SHP647-301 or SHP647 302) baseline in the composite score of subject-reported symptoms using daily e diary and centrally read endoscopy of at least 2 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding ≥1 point or a subscore for rectal bleeding ≤1.
• Mucosal healing, based on endoscopic and histologic assessment, at the Week 52 visit. Mucosal healing is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and centrally read Geboes score of ≤2.
• Glucocorticoid-free clinical remission at Week 52, among subjects using glucocorticoids in study SHP647-303 baseline. Glucocorticoid-free clinical remission is defined as clinical remission in addition to not requiring any treatment with glucocorticoids for at least 4 weeks prior to the Week 52 visit. Clinical remission is defined as stool frequency subscore of 0 or 1 with at least a 1-point change from induction study (SHP647-301 or SHP647-302) baseline in stool frequency subscore, and rectal bleeding subscore of 0, at the Week 52 visit.
• Glucocorticoid-free remission at Week 52, among subjects using glucocorticoids in study SHP647-303 baseline. Glucocorticoid-free remission is defined as remission in addition to not requiring any treatment with glucocorticoids for at least 4 weeks prior to the Week 52 visit. Remission is defined as a composite score of subject-reported symptoms using daily e diary and endoscopy, with stool frequency subscore of 0 or 1 with at least a 1-point change from induction study (SHP647-301 or SHP647-302) baseline, and rectal bleeding subscore of 0, and endoscopic subscore of 0 or 1 (modified, excludes friability).

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 52 visit

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

25 mg or 75 mg ontamalimab

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

337

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Bosnia and Herzegovina

Brazil

Canada

Colombia

Israel

Japan

Korea, Republic of

Lebanon

Mexico

New Zealand

Russian Federation

Serbia

South Africa

Turkey

Ukraine

United States

Austria

Belgium

Bulgaria

Croatia

Czechia

France

Germany

Greece

Hungary

Ireland

Italy

Lithuania

Netherlands

Poland

Portugal

Romania

Slovakia

Spain

Switzerland

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The Study Completion Date is defined as the date the final subject, across all sites, completes their final protocol-defined assessment. Please note that this includes the follow-up visit or contact, whichever is later.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

679

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Adolescents (16-17 years)

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

305

F.4.2.2

In the whole clinical trial

772

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

At the end of the 52 week treatment period, the subject will either enter the LTS study (SHP647 304) or the 12 week safety follow up period.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-11-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-03-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-07-01

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