Clinical Trials Register

Summary
EudraCT Number:	2016-003246-93
Sponsor's Protocol Code Number:	D3461C00008
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:	2016-12-13
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2016-003246-93

A.3

Full title of the trial

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study Characterizing the Pharmacokinetics, Pharmacodynamics, and Safety of Anifrolumab following subcutaneous administration in Adult Systemic Lupus Erythematosus Subjects with Type I Interferon test high result and active skin manifestations

Wieloośrodkowe, randomizowane, prowadzone metodą podwójnie ślepej próby, kontrolowane z zastosowaniem placebo, badanie kliniczne fazy 2 mające na celu określenie farmakokinetyki, farmakodynamiki i bezpieczeństwa stosowania anifrolumabu podawanego podskórnie u dorosłych pacjentów z rozpoznaniem tocznia rumieniowatego układowego z wysokim wynikiem badania interferonu typu I i aktywnymi zmianami skórnymi

A.3.1

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

The purpose of this study is to investigate how a new experimental medication called anifrolumab is distributed in the body when given as subcutaneous (under the skin) injections to subjects with the autoimmune disease called Systemic Lupus Erythematosus (SLE), also known as Lupus. The study will also explore if anifrolumab may improve Lupus skin symptoms.

Celem badania jest poznanie jak nowy eksperymentalny lek o nazwie anifrolumab rozchodzi się wewnątrz organizmu po podaniu podskórnym (zastrzyk podawany pod skórę) u chorych z chorobą autom immunologiczną o nazwie toczeń rumieniowaty układowy, zwaną także toczniem. Badanie będzie także oceniało, czy anifrolumab
może korzystnie wpłynąć na objawy skórne tocznia.

A.4.1

Sponsor's protocol code number

D3461C00008

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	Astrazeneca AB
B.1.3.4	Country	Sweden
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	AstraZeneca
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca
B.5.2	Functional name of contact point	Clinical Trial Transparency
B.5.3	Address:
B.5.3.1	Street Address	Karlebyhus, Astraallén
B.5.3.2	Town/ city	Södertälje
B.5.3.3	Post code	151 85
B.5.3.4	Country	Sweden
B.5.6	E-mail	ClinicalTrialTransparency@astrazeneca.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	Anifrolumab
D.3.2	Product code	MEDI-546
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	ANIFROLUMAB
D.3.9.1	CAS number	1326232-46-5
D.3.9.2	Current sponsor code	MEDI-546
D.3.9.3	Other descriptive name	Immunoglobulin G1, anti-(human type I interferon receptor) (human monoclonal MEDI-546 heavy chain), disulfide with human monoclonal MEDI-546-chain, dimer
D.3.9.4	EV Substance Code	SUB128931
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	150
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

Systemic Lupus Erythematosus

Toczeń rumieniowaty układowy

E.1.1.1

Medical condition in easily understood language

Lupus, an autoimmune disease

Toczeń, choroba autoimmunologiczna

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

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 characterize the pharmacokinetics and pharmacodynamics of anifrolumab.

Scharakteryzowanie farmakokinetyki (PK) i farmakodynamiki (PD) anifrolumabu

E.2.2

Secondary objectives of the trial

1. To characterize the safety and tolerability anifrolumab
2. To characterize the immunogenicity of anifrolumab

1.Scharakteryzowanie bezpieczeństwa i tolerancji anifrolumabu
2.Scharakteryzowanie immunogenności anifrolumabu

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age 18 through 70 years
2. Diagnosis of paediatric or adult SLE for > 24 weeks and fulfilling ≥4 of the 11 ACR classification criteria with at least one being:
-Positive antinuclear antibody (ANA) or
-Elevated anti-dsDNA antibodies or
-anti-Smith (anti-Sm) antibodies
3. Interferon high test result
4. CLASI activity score ≥ 10
5. Currently receiving at least 1 of the following for treatment of SLE:
• Oral prednisone or equivalent of ≤40 mg/day) for a minimum of 2 weeks prior to signing the ICFand with stable dosefor at least 2 weeks prior to randomization
• Any of the following medications for at least 12 weeks prior to signing the ICF, and at a stable doses for at least 8 weeks prior to randomization:
(i) Azathioprine ≤200 mg/day
(ii) Antimalarials (eg, chloroquine, hydroxychloroquine, quinacrine)
(iii) Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day
(iv) Oral, subcutaneous (SC), or intramuscular methotrexate ≤25 mg/week
(v) Mizoribine ≤150 mg/day
6. Must not have signs of active or latent TB.
7. Must not be pregnant or breastfeeding

1.Wiek od 18 do 70 lat podczas oceny przesiewowej
2.Rozpoznanie SLE u dziecka lub osoby dorosłej ≥24 tygodnie przed podpisaniem ICF
oraz spełnienie co najmniej 4 z 11 kryteriów klasyfikacji ACR dla SLE, w tym co najmniej jednego spośród następujących kryteriów:
•dodatni wynik badania w kierunku przeciwciał przeciwjądrowych (ANA)
•podwyższony powyżej normy poziom przeciwciał anty-dsDNA
•podwyższony powyżej normy poziom przeciwciał anty-Smith (anty-Sm)
3.Podwyższony wynik badania IFN typu I
4.Wynik oceny aktywności CLASI ≥10 podczas oceny przesiewowej
5.Aktualne stosowanie, co najmniej 1 spośród następujących metod leczenia SLE:
• prednizon doustny w dawce ≤40 mg/dobę lub równoważna dawka innego
kortykosteroidu, przez co najmniej 2 tygodnie przed podpisaniem ICF; dawka prednizonu doustnego lub równoważna dawka innego kortykosteroidu musi pozostawać stabilna przez co najmniej 2 tygodnie przed randomizacją.
• Dowolne spośród następujących leków podawane, przez co najmniej 12 tygodni przed podpisaniem ICF, przy utrzymaniu stabilnej dawki, przez co najmniej 8 tygodni przed randomizacją:
(i) Azatiopryna ≤200 mg/dobę
(ii) Leki przeciwmalaryczne (np. chlorochina, hydroksychlorochina, kwinakryna)
(iii) Mykofenolan mofetylu ≤2 g/dobę lub kwas mykofenolowy ≤1,44 g/dobę
(iv) Podawany doustnie, podskórne (SC) lub domięśniowo metotreksat ≤25 mg/tydzień
(v) Mizorybina ≤150 mg/dobę
6.Niewystępowanie w wywiadzie utajonej ani aktywnej gruźlicy
7.Kobiety nie mogą być w ciąży ani karmić piersią

E.4

Principal exclusion criteria

1. Active severe or unstable neuropsychiatric SLE
2. Active severe SLE-driven renal disease
3. Any severe herpes infection at any time
4. HBV, HCV, or HIV infection.
5. Known history of a primary immunodeficiency (splenectomy, or any underlying condition predisposing for infection
6. Receipt of any investigation product within 4 weeks or 5 half -lives prior to signing of the ICF
7. History of cancer, apart from:
- Squamous or basal cell carcinoma of the skin if successfully treated
- Cervical cancer in situ if successfully treated

1.Aktywny ciężki lub niestabilny, neuropsychiatryczny SLE
2.Aktywna, ciężka związana z SLE choroba nerek,
3.Dowolne ciężkie zakażenie wirusem ospy wietrznej i półpaśca
4.Potwierdzony dodatni wynik badania w kierunku zapalenia wątroby typu B,
zapalenia wątroby typu C oraz zakażenia HIV
5.Stwierdzony w wywiadzie pierwotny niedobór odporności (np. pospolity zmienny niedobór odporności), stan po splenektomii lub jakakolwiek choroba podstawowa, która predysponuje pacjenta do występowania zakażeń.
6.Przyjmowanie jakiegokolwiek IP (małej cząsteczki lub leku biologicznego) w ciągu
4 tygodni lub 5 okresów półtrwania przed podpisaniem ICF, w zależności od tego, który okres jest dłuższy.
7.Nowotwór złośliwy w wywiadzie, z wyjątkiem:
- raka płaskonabłonkowego lub podstawnokomórkowego skóry po doszczętnym leczeniu
- raka in situ szyjki macicy po doszczętnym leczeniu

E.5 End points

E.5.1

Primary end point(s)

• Anifrolumab concentration and PK parameters, e.g., maximum concentration (Cmax) after first IP dose and trough concentration (Ctrough) after subsequent dosing. Additional PK parameters may be determined where appropriate.
• 21-gene type I IFN signature score and neutralization ratio (relative to baseline)

•Stężenia anifrolumabu i parametry PK, w tym maksymalne stężenie (Cmax) po podaniu pierwszej dawki i minimalne stężenie (Ctrough) po podaniu kolejnej dawki. Dodatkowe parametry PK mogą zostać dookreślone.
•21-genowa sygnatura PD IFN typu 1 i wskaźnik neutralizacji (w odniesieniu do stanu wyjściowego)

E.5.1.1

Timepoint(s) of evaluation of this end point

12 Weeks

12 tygodni

E.5.2

Secondary end point(s)

Safety and tolerability variables including:
• Adverse events (AEs) and serious adverse events (SAEs)
• Adverse events of special interest (AESIs) including herpes zoster, influenza, opportunistic infections, tuberculosis (TB), malignancies, non-SLE related vasculitis, anaphylaxis, and major adverse cardiovascular events (MACE)
• Laboratory variables
• Physical examinations
• Vital signs
• ECG
Immunogenicity as assessed by measurement of anti-drug antibodies (ADA).

Zmienne dotyczące bezpieczeństwa i tolerancji, włączając:
•Zdarzenia niepożądane (AE) i ciężkie zdarzenia niepożądane (SAE);
•Zdarzenia niepożądane o szczególnym znaczeniu (AESI), w tym półpasiec, grypa, zakażenia oportunistyczne, ciężkie zakażenia nieoportunistyczne, gruźlica (TB), nowotwory złośliwe, zapalenie naczyń niezwiązane z SLE, anafilaksja i poważne zdarzenia niepożądane dotyczące układu sercowo-naczyniowego (MACE),
•Parametry laboratoryjne,
•Badania przedmiotowe,
•Podstawowe parametry życiowe
•Badania EKG
Immunogenność oceniana na podstawie pomiaru przeciwciała przeciwko lekowi (ADA)

E.5.2.1

Timepoint(s) of evaluation of this end point

52 weeks

52 tygodnie

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

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Dane zostaną odślepione dla sponsora, kiedy wszyscy pacjenci zakończą wizytę w tygodniu 12.

Sponsor will be unblinded after all patients complete week 12 visit.

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

Hungary

Korea, Republic of

Poland

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

Last Patient Last Visit

LVLS (Last Visit Last Subject)

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

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)

None

Nie dotyczy

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

2017-01-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-12-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-12-17

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