Clinical Trials Register

Summary
EudraCT Number:	2017-000574-11
Sponsor's Protocol Code Number:	SHP647-304
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-11-27
Trial 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

Greece - EOF

A.2

EudraCT number

2017-000574-11

A.3

Full title of the trial

A Phase 3 Long-term Safety Extension Study of SHP647 in Subjects with Moderate to Severe Ulcerative Colitis or Crohn’s Disease (AIDA)

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 long term in the treatment of moderate to severe Ulcerative Colitis or Crohn’s Disease (AIDA)

A.3.2

Name or abbreviated title of the trial where available

AIDA

A.4.1

Sponsor's protocol code number

SHP647-304

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03283085

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	Melanie Ivarsson
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	0016175849253
B.5.5	Fax number	0017814822954
B.5.6	E-mail	mivarsson0@shire.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	Anti-MAdCAM antibody
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	Anti-MAdCAM antibody
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ulcerative colitis or Crohn’s Disease

E.1.1.1

Medical condition in easily understood language

Long-term condition that results in inflammation and ulcers of the colon and rectum or long-term condition that results in inflammation of the the gastrointestinal tract.

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	10017947 - Gastrointestinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10011401
E.1.2	Term	Crohn's disease
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

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 safety and tolerability of long-term treatment with SHP647 in subjects with moderate to severe UC or CD.

E.2.2

Secondary objectives of the trial

Secondary - Subjects with Ulcerative Colitis:
 To evaluate the effect of long-term SHP647 treatment on clinical outcomes (including remission over time
based on composite score of patient-reported symptoms using daily diary and locally read endoscopy,
Mayo-based remission over time, clinical remission over time, partial Mayo score over time).
 To evaluate the effect of long-term SHP647 treatment on endpoints related to endoscopic healing.
Secondary - Subjects with Crohn’s Disease:
 To evaluate the effect of long-term SHP647 treatment on clinical outcomes (including 2 item PRO based
clinical response over time, 2 item PRO based and CDAI-based clinical remission over time.
 To evaluate the effect of long-term SHP647 treatment on endpoints related to endoscopic outcomes
(enhanced endoscopic response as well as endoscopic healing).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects with Ulcerative Colitis
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 been previously enrolled in study SHP647-301, SHP647 302, or SHP647-303, and reached 1 of the following clinical trial milestones:
- Completed the Week 12 visit in induction study SHP647-301 or SHP647 302, and did NOT achieve a clinical response. Clinical response is defined as: 1) a decrease from 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 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.
- Completed the Week 52 visit in maintenance study SHP647-303.
- Withdrew early from maintenance study SHP647-303 due to treatment failure, defined by an endoscopic subscore that has increased by at least 1 point over baseline in the maintenance study or a value ≥2 plus an increase in clinical subscore (stool frequency + rectal bleeding score) of at least 2 points. Centrally read endoscopic subscores will be used to determine treatment failure.
4. 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.

Subjects with Crohn’s Disease
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 been previously enrolled in study SHP647-305, SHP647 306, or SHP647-307, and reached 1 of the following clinical trial milestones:
- Completed the Week 16 visit in induction study SHP647-305 or SHP647 306, and did NOT meet the efficacy criteria (clinical and/or endoscopic response/remission as appropriate) for entry into maintenance study SHP647-307.
- Completed the Week 52 visit in maintenance study SHP647-307.
- Withdrew early from maintenance study SHP647-307 due to treatment failure (or were considered to have failed treatment, at the time of the last visit in study SHP647-307), as defined in the SHP647-307 protocol.
4. Subjects receiving any treatment(s) for CD described in Section 5.3.1, 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

Exclusion Criteria – Subjects with UC:
Subjects are excluded from the study if any of the following criteria are met:
1. Subjects who had major protocol deviation(s) (as determined by the sponsor) in previous studies.
2. Subjects who permanently discontinued investigational product because of an AE, regardless of relatedness to investigational product, in previous studies.
3. Subjects who are likely to require major surgery for UC/CD.
4. Subjects are females who became pregnant during study SHP647-301, SHP647-302, or SHP647-303, females
who are planning to become pregnant during the study period, or males or females of childbearing potential
not agreeing to continue using appropriate contraception methods 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 electrocardiogram (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 previous studies and who have been advised to require treatment for latent or active disease, but who are without a generally accepted course of treatment.

Exclusion Criteria – Subjects with CD:
Subjects are excluded from the study if any of the following criteria are met:
1. Subjects who had major protocol deviation(s) (as determined by the sponsor) in study SHP647-305,
SHP647-306, or SHP647-307.
2. Subjects who permanently discontinued investigational product because of an adverse event (AE), regardless
of relatedness to investigational product, in study SHP647-305, SHP647-306, or SHP647-307.
3. Subjects who are likely to require major surgery for CD or developed acute severe complications of CD (with
or without fulfilling the treatment failure criteria in the maintenance study) that required immediate
intervention (eg, need for immediate biologic treatment with proven effect) and/or CDAI score >450.
4. Subjects are females who became pregnant during study SHP647-305, SHP647-306, or SHP647-307, females
who are planning to become pregnant during the study period, or males or females of childbearing potential
not agreeing to continue using appropriate contraception methods 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.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is assessment of safety as measured by: incidence and severity of AEs; incidence and nature of serious infections; actual values and change from baseline, as well as the incidence of abnormalities in laboratory tests, ECGs, and vital signs; and antidrug antibodies.

E.5.1.1

Timepoint(s) of evaluation of this end point

Please refer to section “Study Schedules” of the Protocol

E.5.2

Secondary end point(s)

Secondary Efficacy Endpoints – Subjects with Ulcerative Colitis:
The secondary efficacy endpoints are as follows:
• Remission based on composite score, assessed yearly and at end of study. Remission is defined as a composite score of patient-reported symptoms using daily diary and locally read endoscopy as follows: 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 locally-read endoscopic subscore of 0 or 1 (modified, excludes friability).
• Remission, based on total Mayo score, assessed yearly and at end of study. Remission is defined as a total Mayo score ≤ 2 with no individual subscore (stool frequency, rectal bleeding, endoscopy [modified, excludes friability], and physician’s global assessment) exceeding 1.
• 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, assessed yearly and at end of study.
• Partial Mayo score of ≤2 with no individual subscore >1 over time. The partial Mayo score does not include the endoscopy subscore.
• Endoscopic remission, as defined by locally read endoscopic subscore 0 or 1 (modified, excludes friability), assessed yearly and at end of study.

Secondary Efficacy Endpoints – Subjects with Crohn’s Disease:
The secondary efficacy endpoints are as follows:
• Clinical remission over time. Clinical remission is defined by 2-item PRO CD daily e-diary subscore of average worst daily abdominal pain ≤3 (based on 11-point NRS over the 7 most recent days) and average daily stool frequency ≤2 of type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days.
• Enhanced endoscopic response, assessed yearly and at end of study, as measured by a decrease in SES-CD of at least 50% from induction study (SHP647-305 or SHP647-306) baseline.
• Clinical remission over time as measured by CDAI <150.
• Clinical remission over time as defined by the following: CD daily e-diary subscores of average worst daily abdominal pain ≤1 (based on the 4-point scale) over the 7 most recent days and average daily stool frequency ≤3 of type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days.
• Both clinical remission by 2-item PRO and enhanced endoscopic response over time (composite endpoint).
• Complete endoscopic healing at end of study, defined as SES-CD=0-2.
All efficacy analyses will be performed using the full-analysis set.
Secondary efficacy endpoints will be summarized by treatment group using descriptive statistics at each assessment visit. Summaries may be presented by the status at entry into the study (eg, induction non-responder, maintenance SHP647 completer, etc). Statistical summaries will include number of subjects and percentages, and 95% confidence intervals.

E.5.2.1

Timepoint(s) of evaluation of this end point

assessed every 24 weeks, yearly, at end of study, or a combination, as detailed in E.5.1

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

Yes

E.6.7

Pharmacodynamic

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Quality of Life

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

25 mg or 75 mg SHP647

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

167

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

Austria

Belgium

Bosnia and Herzegovina

Brazil

Bulgaria

Canada

Colombia

Croatia

Czech Republic

Estonia

France

Germany

Greece

Hungary

Ireland

Israel

Italy

Japan

Korea, Republic of

Lithuania

Mexico

Netherlands

New Zealand

Poland

Portugal

Romania

Russian Federation

Serbia

Slovakia

South Africa

Spain

Switzerland

Ukraine

United Kingdom

United States

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:

247

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:

247

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

2158

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

967

F.4.2.2

In the whole clinical trial

2453

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 this study patients will return to standard of care.

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

2019-02-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-02-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-12-13

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