Clinical Trials Register

Summary
EudraCT Number:	2017-003652-22
Sponsor's Protocol Code Number:	INCB50465-206
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-03-29
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

Austria - BASG

A.2

EudraCT number

2017-003652-22

A.3

Full title of the trial

A Phase 2, Open-Label Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia

A.3.1

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

A Phase 2, Open-Label Study of INCB050465 in Participants With Autoimmune Hemolytic Anemia (AIHA)

A.4.1

Sponsor's protocol code number

INCB50465-206

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03538041

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	Incyte Coorporation
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	Incyte Corporation
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	Incyte Corporation
B.5.2	Functional name of contact point	Medical Information
B.5.3	Address:
B.5.3.1	Street Address	1801 Augustine Cut-Off
B.5.3.2	Town/ city	Wilmington
B.5.3.3	Post code	DE 19803
B.5.3.4	Country	United States
B.5.6	E-mail	globalmedinfo@incyte.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	INCB050465 1 mg
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	not yet assigned
D.3.9.2	Current sponsor code	INCB050465
D.3.9.3	Other descriptive name	INCB050465 HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB183790
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	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	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	INCB050465 2.5 mg
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	not yet assigned
D.3.9.2	Current sponsor code	INCB050465
D.3.9.3	Other descriptive name	INCB050465 HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB183790
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	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	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

Autoimmune Hemolytic Anemia (AIHA), immunohemolytic anemia, autoimmune hemolytic anemia, immune complex hemolytic anemia.
Warm AIHA, Cold AIHA

E.1.1.1

Medical condition in easily understood language

Autoimmune Hemolytic Anemia (AIHA)

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10003825
E.1.2	Term	Autoimmune hemolytic anemia
E.1.2	System Organ Class	100000004851

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the efficacy of INCB050465 in the treatment of participants with AIHA.
• Proportion of participants attaining a CR (defined as hemoglobin > 12 g/dL not attributed to transfusion effect and the normalization of hemolytic markers) at any visit from Week 6 to Week 12.
• Proportion of participants attaining a PR (defined as hemoglobin 10-12 g/dL or ≥ 2 g/dL increase from baseline not attributed to transfusion effect and the normalization of hemolytic markers) at any visit from Week 6 to Week 12.

To evaluate the safety of INCB050465 administered as repeat doses in participants with AIHA.
• Safety and tolerability will be assessed by monitoring AEs, measuring vital signs and ECGs, and conducting clinical laboratory blood and urine sample assessments.

E.2.2

Secondary objectives of the trial

To further evaluate the efficacy of INCB050465 in the treatment of participants with AIHA.
• Proportion of participants attaining a CR during postbaseline visits.
• Proportion of participants attaining a PR during postbaseline visits.
• Proportion of participants attaining a ≥ 2 g/dL increase in hemoglobin from baseline.
• Mean, change, and percentage change from baseline of hemoglobin.
• Proportion of participants requiring transfusions.
• Proportion of participants who achieve normalization of hemolytic markers. (Hemolysis markers: hemoglobin, haptoglobin, LDH, reticulocyte count, total bilirubin, and direct/indirect bilirubin.)
• Change of daily usage of prednisone.
• FACIT-F sub-scale assessment.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A participant who meets all of the following criteria may be included in the study:
1. Men or women, aged 18 years or older.
2. Diagnosis of AIHA based on the presence of hemolytic anemia and serological evidence of anti-erythrocyte antibodies, detectable by the DAT as follows:
a. Warm: DAT positive for IgG only or IgG plus C3d
b. Cold (CAD): DAT positive for C3d only, with cold agglutinins of I specificity
c. Mixed: DAT positive for IgG and C3d, with coexistence of warm autoantibodies and high titer cold agglutinins
3. Participants who have disease progression after treatment with standard therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment. There is no limit to the number of prior treatment regimens.
4. Hemoglobin 7 to 10 g/dL. (as determined by local laboratory).
5. No evidence of a lymphoproliferative malignancy or other autoimmune-related underlying conditions (eg, systemic lupus erythematosus, Castleman's disease, Sjögren's syndrome, or other autoimmune diseases).
6. ECOG performance status score of 0 to 2.
7. Willingness to avoid pregnancy or fathering children based on the criteria below:
a. Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR postmenopausal, defined by last menstrual period > 12 months before screening and confirmed by FSH).
b. Woman of childbearing potential who has a negative serum pregnancy test at screening and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through at least 93 days after the last dose of study drug. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participant and her understanding confirmed.
c. Man who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through at least 93 days after the last dose of study drug. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participant and his understanding confirmed.
8. Able to comprehend and willing to sign an ICF.
9. Willingness to receive PJP prophylaxis during the study period.

E.4

Principal exclusion criteria

A participant who meets any of the following criteria will be excluded from the study:
1. Pregnant or breastfeeding women.
2. Concurrent conditions and history of other diseases:
a. History or clinical manifestations of significant unstable metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, or psychiatric disorders.
b. Current or previous malignancy within 5 years of study entry, except basal or squamous cell skin cancer with removal considered to be curative, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval.
c. Clinically significant cardiac disease, including unstable angina, acute myocardial infarction, and or cardiac conduction issues within 6 months of the date of study drug administration.
d. Current New York Heart Association Class II to IV congestive heart failure or uncontrolled arrhythmia.
3. Inadequate hematologic function defined as follows (as determined by local laboratory):
a. ANC < 1.5× 109/L.
b. Platelet count < 100 × 109/L.
4. Severely impaired liver function (Child-Pugh Class C) or ALT or AST ≥ 2 × ULN on repeated assessment.
5. Impaired renal function with estimated creatinine clearance less than 45 mL/min.
6. Anti-phospholipid antibodies positive or elevated anti-streptolysin antibodies.
7. Hepatitis B (HBV) or hepatitis C (HCV) infection: Participants who are positive for the hepatitis B surface antibody or hepatitis B core antibody, will be eligible if they are negative for HBV-DNA; these participants should be considered for prophylactic antiviral therapy. Participants who are positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
8. Known HIV infection or positivity on immunoassay. Note: HIV screening test is optional for participants enrolled in the United States, but participants with known HIV infection enrolled in the United States will be excluded.
9. History or presence of an abnormal ECG, that in the investigator’s opinion is clinically meaningful. Participants with screening QTc interval> 470 milliseconds for males and > 480 milliseconds for females (corrected by Fridericia) are excluded. In the event that a single QTcF is >470 milliseconds for males or >480 milliseconds for females, the participant may enroll if the average QTcF for 3 ECGs is <470 milliseconds for males and <480 milliseconds for females.
10. Use of the following medications:
a. Treatment with rituximab within 3 months of the baseline visit.
b. Use of immunosuppressive therapy within 28 days of the baseline visit. Immunosuppressive therapy includes, but is not limited to, cyclosporine A, tacrolimus, or high-dose corticosteroids. Participants receiving corticosteroids must be at a dose level ≤ 20 mg/day (prednisone or equivalent corticosteroid dose) within 14 days of the baseline visit.
c. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment or exposure to a live vaccine within 28 days of the baseline visit.
d. Use or expected use during the study of any prohibited medications, including potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is longer) before the baseline visit.
e. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before the baseline visit with another investigational medication, or current enrollment in another investigational drug protocol.
f. Use of any prohibited medications within 14 days or 5 half-lives (whichever is longer) before the baseline visit.
11. Known hypersensitivity or severe reaction to INCB050465 or its excipients.
12. Unable to swallow oral medication, malabsorption syndrome, disease significantly affecting gastrointestinal function, total resection of the stomach or small bowel, ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
13. Current alcohol or drug use that, in the opinion of the investigator, will interfere with the participant's ability to comply with the dose regimen and study evaluations.
14. Participants who, in the opinion of the investigator, are unable or unlikely to comply with the dose regimen and study evaluations.
15. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.

E.5 End points

E.5.1

Primary end point(s)

Proportion of participants attaining a CR (defined as hemoglobin >12 g/dL not attributed to transfusion effect and the normalization of hemolytic markers) at any visit from Week 6 to Week 12.
• Proportion of participants attaining a PR (defined as hemoglobin 10-12 g/dL or at least ≥ 2 g/dL increase from baseline not attributed to transfusion effect and the normalization of hemolytic markers) at any visit from Week 6 to Week 12.

E.5.1.1

Timepoint(s) of evaluation of this end point

Efficacy: From Week 6 to Week 12
Safety: Throughout the study

E.5.2

Secondary end point(s)

• Proportion of participants attaining a CR during postbaseline visits.
• Proportion of participants attaining a PR during postbaseline visits.
• Proportion of participants attaining a ≥ 2 g/dL increase in hemoglobin from baseline.
• Mean, change, and percentage change from baseline of hemoglobin.
• Proportion of participants requiring transfusions.
• Proportion of participants who achieve normalization of hemolytic markers. (Hemolysis markers: hemoglobin, haptoglobin, LDH, reticulocyte count, total bilirubin, and direct/indirect bilirubin.)
• Change of daily usage of prednisone.
• FACIT-F sub-scale assessment.

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy: Throughout the study
PK: Week 1: predose; week 2 and week 8: predose, at 1h +- 10min, at 2h +- 10min and at 4h +- 30 min; week 12: predose
PD: DAT for IgG and C3b and cold agglutinin levels: at screening and week 12; reticulocyte count, haptoglobin, total bilirubin, direct/indirect bilirubin, and LDH: at screening, day 1, weeks 1, 2, 4, 6, 8 and 10; complement assessment (CH50, C3, and C4): at day 1 and week 12

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

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

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

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

Austria

France

Italy

United States

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

The end of the study will occur when all participants have completed all applicable follow-up assessments.

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:

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

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

F.4.2.2

In the whole clinical trial

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)

standard of care for treatment of AIHA

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

2018-07-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-18

P. End of Trial
P.	End of Trial Status	Ongoing

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