Clinical Trials Register

Summary
EudraCT Number:	2019-002698-74
Sponsor's Protocol Code Number:	B7541007
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-02-11
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2019-002698-74

A.3

Full title of the trial

A PHASE 2B, MULTICENTER, RANDOMIZED, DOUBLEBLIND,
PLACEBO CONTROLLED DOSE-RANGING
STUDY TO EVALUATE THE EFFICACY, SAFETY, AND
PHARMACOKINETICS OF PF-06480605 IN ADULT
PARTICIPANTS WITH MODERATE TO SEVERE
ULCERATIVE COLITIS

A.3.1

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

A study to evaluate the efficacy and safety of PF 06480605 in adult participants with moderate to severe ulcerative colitis

A.3.2

Name or abbreviated title of the trial where available

Tuscany 2

A.4.1

Sponsor's protocol code number

B7541007

A.5.4

Other Identifiers

Name:

US IND Number

Number:

129188

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	Pfizer 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	Pfizer 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	Pfizer Inc
B.5.2	Functional name of contact point	Clinical Trials.gov Call Centre
B.5.3	Address:
B.5.3.1	Street Address	235 East 42nd Street
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	10017
B.5.3.4	Country	United States
B.5.4	Telephone number	0018007181021
B.5.6	E-mail	ClinicalTrials.gov_Inquiries@pfizer.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.3.1	Product name	PF-06480605
D.3.2	Product code	PF-06480605
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	PF-06480605
D.3.9.2	Current sponsor code	PF-06480605
D.3.9.3	Other descriptive name	Anti-TL1A
D.3.9.4	EV Substance Code	SUB181859
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	100
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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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	Yes
D.3.11.13.1	Other medicinal product type	PF-06480605 neutralizes the binding and subsequent signaling of TL1A to its functional receptor DR3 on immune cells of the innate and adaptive immune system.

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

A phase 2b randomised, double-blind, placebo controlled dose-ranging study in Adults with Moderate to Severe Ulcerative Colitis

E.1.1.1

Medical condition in easily understood language

Adults with Moderate to Severe Inflammatory Bowel Disease

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	20.0
E.1.2	Level	HLT
E.1.2	Classification code	10009888
E.1.2	Term	Colitis (excl infective)
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

1. To evaluate the efficacy of PF-06480605 in induction of clinical remission at Week 14 in participants with moderate to severe active UC.
2. To evaluate the safety and tolerability of PF-06480605 during the induction period (from baseline to Week 14) and during the chronic therapy period (from Week 14 to the End of Study Visit)

E.2.2

Secondary objectives of the trial

1. To evaluate the efficacy of PF-06480605 in inducing remission at Week 14 in participants with moderate to severe active UC.
2. To valuate the efficacy of PF-06480605 on endoscopic appearance at Week 14.
3. To characterize the PK of PF-06480605 during the induction period. To evaluate disease and pathway related biomarkers (ie, hsCRP and fecal calprotectin and serum sTL1A)
Tertiary Objectives
1. To evaluate the effect of PF-06480605 on clinical outcomes and quality of life.
2. To evaluate the effect of PF 06480605 compared to placebo on histopathology score.
3. To collect non banked samples (eg, intestinal biopsies, stool for microbiome and metabolomic analysis, serum for analysis of proteins and metabolomic profiling and blood for RNA analysis) for exploratory research.
4. To enable exploratory research through collection of banked biospecimens
5 .To conduct additional exploratory immunogenicity assessments.
6.To characterize the immunogenicity of PF-06480605

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female participants 18 to 75 years of age.
2. A diagnosis of UC for ≥3 months with endoscopy and pathology reports supporting the diagnosis, disease duration, and extent of disease.
3. Moderate to severe active UC as defined by a Total Mayo Score of ≥6, and an endoscopic subscore of ≥2.
4. Active disease beyond the rectum (>15 cm from the anal verge).
5. Failed or be intolerant of at least 1 of the following treatments.
Steroids, Immunosuppressants (azathioprine [AZA],
6-mercaptopurine [6-MP] or methotrexate [MTX]),
Anti-TNF inhibitors (eg, infliximab, adalimumab, or golimumab),
Anti-integrin inhibitors (eg, vedolizumab),
Anti-IL-12/23 inhibitors (eg, ustekinumab),
JAK inhibitors (eg, tofacitinib).
Participants currently receiving treatments for UC are eligible providing they have been and are anticipated to be on stable dose for the duration of the study.
6. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
7. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.

E.4

Principal exclusion criteria

1. Diagnosis of ischemic colitis, infectious colitis, radiation colitis,
microscopic colitis, indeterminate colitis, or findings suggestive of Crohn’s disease (eg, skip lesions, fistulae/perianal disease, non-necrotizing granulomas, etc.).
2. Clinical signs of fulminant colitis or toxic megacolon.
3. Imminent need for surgery or with elective surgery scheduled to
occur during the study.
4. Evidence of colonic dysplasia, adenomas, or neoplasia
5. Participants who meet either of the 2 criteria below are considered at risk for colonic dysplasia, adenomas, or neoplasia and must have a colonoscopy prior to randomization:
a. If the participant has had extensive (ie greater than left sided) colitis for equal to or greater than 8 years or disease limited to left side of colon (ie distal to splenic flexure) for equal to or greater than 10 years, regardless of age, a colonoscopy within 1 year of screening visit is required to survey for dysplasia.
b. If the participant is equal to or greater than 50 years of age, a colonoscopy within 10 years of screening is required to exclude adenomatous polyps.
Participants with adenomatous polyps identified on screening endoscopy will be eligible after complete polypectomy and follow up surveillance per local guidelines is negative.
Or, If the participant is over 50 years of age, a colonoscopy within 10 years of screening is required to exclude adenomatous polyps. Participants with adenomatous polyps identified on screening endoscopy will be eligible after complete polypectomy and follow-up surveillance per local guidelines is negative.
6. Clinically significant infections within 6 months of baseline (eg those requiring hospitalization or parenteral antimicrobial therapy, or opportunistic infections)
7. Cancer or history of cancer or lymphoproliferative disease within 5 years of baseline (with the exception of adequately treated or excised non-metastatic basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ).
8. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or interfere with the interpretation of study results.
9. Use of prohibted prior/concomitant medications
10. Known exposure to anti-TL1A (PF 06480605) or any type of anti-TL1A therapy.
11. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of investigational product used in this study (whichever is longer). Note: local regulations or other factors may require more than 30 days.
12. A 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
13. Chest Radiograph or computed tomography scan showing abnormalities.
14. Infected with tuberculosis, (TB): Any evidence of untreated latent or active TB infection.
15. Presence of active enteric infections: Known pathogenic bacterial, parasitic, fungal infections, including Clostridium difficile.
16. Infected with human immunodeficiency virus, (HIV), Hepatitis B or C viruses.
17. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat, if deemed necessary:
• Hemoglobin 8.0 g/dL or hematocrit 30% (0.30 v/v);
• Absolute lymphocyte count (ALC) 0.8 x 109/L (800/mm3);
• Absolute neutrophil count (ANC) 1.2 x 109/L (1200/mm3);
• Platelet count 100 x 109/L (100,000/mm3);
• Aspartate aminotransferase, (AST) or alanine aminotransferase, (ALT) ≥2.0 times the upper limit of normal (ULN);
• Total bilirubin level ≥1.5 times the ULN; participants with a history of Gilbert’s syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin in ≤ ULN
18. History of alcohol or drug abuse (per the investigator’s discretion) that would prevent the participant from being compliant with study visits and required procedures.
19. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.

E.5 End points

E.5.1

Primary end point(s)

Proportion of participants achieving clinical remission (defined as a Total Mayo Score ≤2, with no individual subscore >1) at Week 14.
Incidence and severity of treatment emergent adverse events (TEAEs) during the induction period.
Incidence of serious adverse events (SAEs)
Incidence of AEs or SAEs leading to discontinuation
Incidence of clinically significant abnormalities in vital signs, ECGs and laboratory values.

E.5.1.1

Timepoint(s) of evaluation of this end point

At weeks 14 and 56 unless otherwise specified above

E.5.2

Secondary end point(s)

Proportion of participants achieving remission (FDA definition 1 - defined as endoscopic subscore = 0 or 1, stool frequency subscore = 0, and rectal bleeding subscore = 0) at Week 14.
Proportion of participants achieving remission (FDA definition 2 - defined as endoscopic subscore = 0 or 1, ≥1 point decrease from baseline to achieve a stool frequency subscore = 0 or 1, and rectal bleeding subscore = 0) at Week 14.
Proportion of participants achieving endoscopic improvement (defined as endoscopic subscore = 0 or 1) at Week 14.
Proportion of participants achieving endoscopic remission (defined as endoscopic subscore = 0) at Week 14.
PF 06480605 trough concentrations during the induction period through Week 14.
Change from screening in fecal calprotectin during the induction period through Week 14.
Change from baseline in hsCRP during the induction period through Week 14.
Change from baseline in serum sTL1A during the induction period through Week 14.
Incidence of development of anti drug antibodies (ADAs) and neutralizing antibodies (NAbs) during the induction period through Week 14.
Proportion of participants achieving sustained clinical remission (ie, clinical remission at both Week 14 and Week 56).
Proportion of participants achieving remission (FDA definition 1 - defined as endoscopic subscore = 0 or 1, stool frequency subscore = 0, and rectal bleeding subscore = 0) at Week 56.
Proportion of participants achieving sustained remission FDA definition 1 (ie, remission FDA definition 1 at both Week 14 and Week 56).
Proportion of participants achieving remission (FDA definition 2 - defined as endoscopic subscore = 0 or 1, ≥1 point decrease from baseline to achieve a stool frequency subscore = 0 or 1, and rectal bleeding subscore = 0) at Week 56.
Proportion of participants achieving sustained remission FDA definition 2 (ie, remission FDA definition 2 at both Week 14 and Week 56).
Proportion of participants achieving endoscopic improvement (defined as endoscopic subscore = 0 or 1) at Week 56.
Proportion of participants achieving sustained endoscopic improvement (ie, endoscopic improvement at both Week 14 and Week 56).
Proportion of participants achieving endoscopic remission (defined as endoscopic sub score = 0) at Week 56.
Proportion of participants achieving sustained endoscopic remission (ie, endoscopic remission at both Week 14 and Week 56).
PF 06480605 concentration from Week 14 through the End of Study Visit.
Change from Week 14 in fecal calprotectin during the chronic therapy period through the End of Study Visit.
Change from Week 14 in hsCRP during the chronic therapy period through the End of Study Visit.
Change from week 14 in serum sTL1A during the chronic therapy period through the End of Study Visit.
Change from baseline through the End of Study Visit in fecal calprotectin.
Change from baseline through the End of Study Visit in hsCRP.
Change from baseline through the End of Study Visit in serum sTL1A.
Incidence of development of anti drug antibodies (ADAs) and neutralizing antibodies (NAbs) from Week 14 through the End of Study Visit.

E.5.2.1

Timepoint(s) of evaluation of this end point

Individual timepoints as detailed above for each endpoint

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

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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

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

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

Australia

Canada

China

Colombia

India

Japan

Mexico

South Africa

Thailand

United States

Austria

France

Poland

Bulgaria

Romania

Spain

Germany

Italy

Belgium

Hungary

Russian Federation

Serbia

Slovakia

Turkey

Ukraine

United Kingdom

E.8.7

Trial has a data monitoring committee

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

A participant is considered to have completed the study if he/she has completed all phases of the study including; screening, induction phase, chronic therapy period, and the follow up portion of the study up through and including visit (Visit 18), approximately 12 weeks post last dose of IP. The end of the study is defined as the date of the last visit (Visit 18), by the last participant across all sites globally.

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

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)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

120

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

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

180

F.4.2.2

In the whole clinical trial

240

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)

No intervention will be provided to study participants at the end of the study.

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

2020-03-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-02-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-10-25

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