Clinical Trials Register

Summary
EudraCT Number:	2020-004529-22
Sponsor's Protocol Code Number:	D3465C00001
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-18
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2020-004529-22

A.3

Full title of the trial

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 3 Study Evaluating the Efficacy and Safety of Subcutaneous Anifrolumab in Adult Patients with Systemic Lupus Erythematosus

Multicentrikus, randomizált, kettős vak, placebo kontrollált, III. fázisú
vizsgálat a szubkután alkalmazott anifrolumab hatásosságának és
biztonságosságának értékelésére szisztémás lupus erythematosusban
szenvedő felnőtt betegek esetében

A.3.1

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

Subcutaneous Anifrolumab in Adult Patients with Systemic Lupus Erythematosus

A.3.2

Name or abbreviated title of the trial where available

Tulip SC

A.4.1

Sponsor's protocol code number

D3465C00001

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
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	Information Center
B.5.3	Address:
B.5.3.1	Street Address	NA
B.5.3.2	Town/ city	NA
B.5.3.3	Post code	NA
B.5.3.4	Country	United States
B.5.6	E-mail	information.center@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	Yes
D.2.1.1.1	Trade name	SAPHNELO
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 in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
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
D.3.9.2	Current sponsor code	MEDI-546
D.3.9.3	Other descriptive name	ANIFROLUMAB
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	Yes
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 in pre-filled syringe
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

Moderate-to-severe Systemic Lupus Erythematosus (SLE)

E.1.1.1

Medical condition in easily understood language

Systemic Lupus Erythematosus is a disease in which the body's own immune system attacks its own cells and tissues, leading to inflammation and damage.

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10042945
E.1.2	Term	Systemic lupus erythematosus
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue 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

To compare efficacy of anifrolumab with placebo on overall disease activity in patients with SLE.

E.2.2

Secondary objectives of the trial

To compare the efficacy of anifrolumab with placebo on improvement in overall disease activity,
and low (or reduced) OCS use
To compare the efficacy of anifrolumab with placebo on the onset of a sustained reduction in disease activity.
To compare the efficacy of anifrolumab with placebo on the onset of first flare.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Patients who have a diagnosis of pediatric or adult SLE according to the ACR 1997 revised criteria for ≥ 24 weeks prior to signing the ICF
2.To be eligible a patient must have SLEDAI-2K ≥ 6 points "Clinical"
SLEDAI-2K ≥4 points coming from clinical components ("Clinical"
SLEDAI-2K") at screening. In addition, the following criteria must be
met:
Clinical SLEDAI of at least ≥ 4 points at Day 1(randomization).
Note: The "Clinical" SLEDAI-2K is the SLEDAI-2K assessment score
without the inclusion of points attributable to any urine or laboratory
results including immunologic measures: Includes points from the
following clinical components: arthritis, myositis, rash, alopecia, mucosal
ulcers, pleurisy, pericarditis, or vasculitis. Excludes points attributed to a fever, an SLE headache, and organic brain syndrome.
Clinical SLEDAI-2K points at screening cannot only be due to alopecia
and mucosal ulcers.
3.At Screening, BILAG-2004 with at least 1 of the following as
confirmed by Disease Activity Central Team Review:
a.BILAG2004 level A disease in ≥ 1 organ system
b.BILAG2004 level B disease in ≥ 2 organ systems
4.Physician’s Global Assessment (PGA) score ≥ 1.0 on a 0 to 3 VAS at Screening
5.Antinuclear antibody, and/or Anti-dsDNA and/oranti-Smith positive at Screening,
6.Must be on stable background standard therapy with antimalarials and/or immunosuppressants and glucocorticoids alone or in combination.
7.Contraception Requirements
Male patients:
All fertile males who are sexually active must use condom from Day 1 until at least 16 weeks after receipt of the final dose of study intervention. It is strongly recommended that the female partner of a male patient also use an effective method of contraception from Table 9 throughout this period.
Male patients must not donate sperm during the course of the study and for 16 weeks after the last dose of the study intervention.
Female patients:
Negative serum β-human chorionic gonadotropin (β-hCG) test at screening (females of childbearing potential only).
Women of child-bearing potential must have a negative urine pregnancy test at randomization (Day 1), prior to administration of study intervention.
Women of non-childbearing potential must be postmenopausal or have been surgically sterilised (for example: bilateral oophorectomy, or complete hysterectomy), which should be documented in the patient's medical records.
Age-specific requirements may apply for a postmenopausal state.
Females of childbearing potential must use 1 highly effective methods of contraception plus a male condom, from Screening until 16 weeks after the final dose of study intervention, unless the patient is surgically sterile (eg, bilateral oophorectomy, tubal ligation or complete hysterectomy), has a sterile/non-fertile male partner, is at least 12 months postmenopausal, or practices sustained abstinence consistent with the patient's lifestyle.
Malignancy:
Females who have been or are sexually active with an intact cervix must have ocumentation of a cervical cancer screening (Pap smear or human papilloma virus [HPV] tests as per local guidelines) with a normal test result within 2 years prior to randomisation. Any abnormal cervical cancer screening
result documented within 2 years prior to randomisation must be repeated to confirm patient eligibility.
Females aged < 25 years, who have never been sexually active or have well-documented HPV vaccination records may not require a cervical cancer screening test.

E.4

Principal exclusion criteria

1.Active severe or unstable neuropsychiatric SLE
2.Active severe SLE-driven renal disease
3.Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the patient to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at Screening.
4.Any severe case herpes zoster infection at any time prior to Week 0 (Day 1),
5.Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization.
6.History of cancer, apart from:
a. Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥ 3 months prior to Week 0 (Day 1)
b. Cervical cancer in situ treated with apparent success with curative therapy ≥ 1 year prior to Week 0 (Day 1)
7.Any history of severe COVID-19 infection eg, prolonged hospitalisation [hospitalisation for observational purposes is not exclusionary] or any prior COVID-19 infection with documented long COVID and/or clinically significant unresolved sequelae.
Any mild/asymptomatic COVID-19 infection (lab confirmed or suspected based on clinical symptoms) within the last 6 weeks prior to first dosing.
8.Lactating, breastfeeding or pregnant females or females who intend to become pregnant or begin breastfeeding anytime from initiation of Screening until 16 weeks following last dose of study intervation.

E.5 End points

E.5.1

Primary end point(s)

BICLA a composite binary response defined by meeting all of the following criteria:
-Reduction of all baseline (BILAG)-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no
BILAG-2004 worsening in other organ systems, as defined by ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG-2004 B
-No worsening from baseline in SLEDAI-2K, where worsening is defined as an increase from baseline of > 0 points in SLEDAI-2K
-No worsening from baseline in patients' lupus disease activity, where worsening is defined by an increase ≥ 0.30 points on a 3 point PGA VAS

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 52

E.5.2

Secondary end point(s)

1.Proportion of patients who are BICLA responders at Week 52, and have maintained low (or reduced) OCS use through Week 52
• Maintained low (or reduced) OCS use is defined as follows:
• If baseline OCS ≥ 10 mg/day an OCS dose of ≤ 7.5 mg/day
prednisone or equivalent must be achieved by Week 40 and an OCS dose ≤ 7.5 mg/day prednisone or equivalent must be maintained from Week 40 to Week 52
• if baseline OCS < 10 mg/day, OCS dose at Week 40 must be less than or equal to OCS dose at baseline, with no increase from Week 40 OCS dose between Week 40 and Week 52.
2.The time from first dose of study intervention during the Double-Blind Study Period to first BICLA response sustained through week 52
3.Time to flare through Week 52 where flare is defined as either 1 or more new BILAG-2004 A or 2 or more new BILAG 2004 B items compared to the previous visit.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. at week 52
2. through week 52
3. through week 52

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

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Imunogenicity

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

Yes

E.8.1.7.1

Other trial design description

an OLE Period; A Follow-up Period;

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

Argentina

Chile

Colombia

Peru

Philippines

Ukraine

Japan

Korea, Republic of

Mexico

Russian Federation

Thailand

United Kingdom

United States

Bulgaria

Germany

Hungary

Poland

Spain

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 end of the study is defined as the date of the last scheduled procedure shown in the SoA for the last patient in the study 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

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:

324

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

360

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)

Patients are to be treated with standard therapy after they have
concluded study treatment. There are no provisions for administration
of study intervention following End of Treatment (EOT) visit (Week 52
for patients not participating in the OLE Period, and Week 104 for
patients participating in the OLE 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

2021-08-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-08-24

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

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