Clinical Trials Register

Summary
EudraCT Number:	2020-002510-40
Sponsor's Protocol Code Number:	DEALSZ-2020-001
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-10-08
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

Germany - PEI

A.2

EudraCT number

2020-002510-40

A.3

Full title of the trial

A multicenter, randomized, double-blind, placebo-controlled, phase 2, 12-week treatment study followed by a 12 week open label phase and a 12-week follow-up period to assess the efficacy and safety of avdoralimab (IPH5401) C5aR blocking antibody in adult patients with chronic spontaneous urticaria resistant to H1-antihistamine treatment.

A.3.1

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

Study for a new medication in Chronic Urticaria.

A.3.2

Name or abbreviated title of the trial where available

CRUSE

A.4.1

Sponsor's protocol code number

DEALSZ-2020-001

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	Charité Universitätsmedizin Berlin
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Innate Pharma
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Charité Universitätsmedizin Berlin
B.5.2	Functional name of contact point	Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	Charitéplatz 1
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	10117
B.5.3.4	Country	Germany
B.5.4	Telephone number	004930450618435
B.5.5	Fax number	004930450518917
B.5.6	E-mail	karen.ottenstein@charite.de

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	avdoralimab
D.3.2	Product code	IPH5401
D.3.4	Pharmaceutical form	Lyophilisate and solvent for 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	Avdoralimab
D.3.9.1	CAS number	2226393-85-5
D.3.9.2	Current sponsor code	IPH5401
D.3.9.3	Other descriptive name	NNCO215-0384
D.3.9.4	EV Substance Code	SUB204079
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)	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/infusion
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

Chronic spontaneous Urticaria

E.1.1.1

Medical condition in easily understood language

Chronic swelling of the skin

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

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	10072757
E.1.2	Term	Chronic spontaneous urticaria
E.1.2	System Organ Class	10040785 - Skin and subcutaneous 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

The primary objective is to assess the explorative efficacy pf avdoralimab (450 mg weekly) as compared to placebo regarding the change in urticaria activity score 7 (UAS7) from baseline to week 12 in adult patients diagnosed with CSU who remain symptomatic despite H1-AH at approved doses.

E.2.2

Secondary objectives of the trial

Efficacy
QoL
Proportion of clinical (MID) responders
Time to first clinical (MID) response
Proportion of complete responders
Time to first complete response
Proportion of non-response (symptom reocurrence after study-drug dis-continuation)
Safety of subjects treated with avdoralimab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient is capable of giving informed consent
2. Patient has given written informed consent before any study related procedures.
3. Patient is able to communicate with the investigator, understands and is willing to comply with the requirements of the study.
4. Male or Female
5. Patient is 18-75 years of age
6. Patient is diagnosed with moderate to severe CSU and refractory to standard of care treatment at the time of randomization, as defined by the following:
a. The presence of itch and hives for ≥ 6 consecutive weeks at any time prior to enrollment despite current use of H1-AH, and
b. Urticaria activity score UAS7 score (range 0-42) ≥ 16, within 7 days prior to randomization (Day 1), and
c. CSU diagnosis for at least 6 months
7. Patient has not been treated with omalizumab or was last treated three months ago and did not respond to omalizumab.
8. Willing and able to complete a daily symptom diary for the duration of the study and adhere to the study visit schedules.
9. Patients must not have more than one missing diary entry in the 7 days prior to randomization. Re-screening may be considered.
10. Male patients who are sexually active with a female partner of childbearing potential must agree to a highly effective form of contraception and have to continue its use for the duration of the study and until at least 6 months (180 days) after the last dose of avdoralimab
11. Women of childbearing potential have to agree to use a highly effective form of contraception and have to continue its use for the duration of the study and until at least 6 months (180 days) after the last dose of avdoralimab:

E.4

Principal exclusion criteria

1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer;
2. Patients whose urticaria is solely due to inducible urticaria
3. Other diseases with symptoms of urticaria or angioedema, including urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency)
4. Any other active skin disease that might confound the study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, etc.)
5. Patients who have received concomitant prohibited medication within the last 3 months prior to screening:
• Anti-IgE therapy (e.g. omalizumab)
• Routine (daily or every other day during 5 or more consecutive days) doses of systemic corticosteroids or other immunosupressants
• Intravenous immunoglobulins
• Biological therapy
• Systemic immunosuppressants
• Live/attenuated vaccines
• Other investigational drug
6. Use of prohibited treatment detailed in protocol (see under 6.5.8 Table 3)
7. Patients with low IgE (≤ 40 kU/l) and without elevated IgG-anti-TPO (≥ 34 kU/l) as well as patients without low IgE and with elevated IgG-anti-TPO
8. History of anaphylaxis.
9. Presence of clinically significant cardiovascular, renal, bronchial, neurological, psychiatric, metabolic or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients.
10. Medical examination or laboratory findings that suggest the possibility of decompensation of co-existing conditions for the duration of the study. Any items that are cause for uncertainty must be reviewed with the Medical Monitor.
11. Inability to comply with study and follow-up procedures.
12. History of malignancy of any organ system (other than localized basal cell carcinoma or actinic keratosis or Bowen disease: carcinoma in situ of skin; carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
13. History or evidence of ongoing drug or alcohol abuse, within the last 6 months prior to randomization.
14. Study personnel or first-degree relatives of investigator(s) .
15. Subjects who live in detention on court order or on regulatory action as per local and national law (see §40 subsection 1 sentence 3 no. 4 Arzneimittelgesetz)
16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

E.5 End points

E.5.1

Primary end point(s)

UAS7

E.5.1.1

Timepoint(s) of evaluation of this end point

Change from baseline (week 1, V1) to the end of week 12

E.5.2

Secondary end point(s)

Efficacy: UAS7, AAS, Angioedema burdened days, HSS7, ISS7; UCT, Rescue medication use per week
QoL: DLQI, Cu-Q2oL, AE-QoL
Proportion of clinical (MID) responders: Clinical responder regarding UAS7, Clinical responder regarding HSS7, Clinical responder regarding ISS7, Clinical responder regarding UCT, Clinical responder regarding CU-Q2oL
Time to first clinical (MID) response: Time to first clinical response regarding UAS7, Time to first clinical response regarding HSS7, Time to first clinical response regarding ISS7, Time to first clinical response regarding UCT, Time to first clinical response regarding CU-Q2oL
Proportion of complete responders: Complete responder regarding UAS7, Complete responder regarding HSS7, Complete responder regarding ISS7 Complete responder regarding UCT, Complete responder regarding AAS, Complete responder regarding CU-Q2oL
Time to first complete response: Time to first complete response regarding UAS7, Time to first complete response regarding HSS7, Time to first complete response regarding ISS7, Time to first complete response regarding UCT, Time to first complete response regarding AAS, Time to first complete response regarding CU-Q2oL
Proportion of non-response (symptom reocurrence after study-drug dis-continuation): Non-response regarding UAS7, Non-response regarding HSS7, Non-response regarding ISS7, Non-response regarding UCT, Non-response regarding AAS
Safety of subjects treated with avdoralimab: This includes physical examination and clinical observation, routine safety laboratory assessments, vital signs, and safety monitoring: frequency of adverse events (AE/SAE/TEAE).

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy: Change from baseline to all assessment time points*
QoL: Change from baseline to all assessment time points*
Proportion of clinical (MID) responders: Change from baseline to all assessment time points*
Time to first clinical (MID) response: Change from baseline to all assessment time points *
Proportion of complete responders: Change from baseline to all assessment time points*
Time to first complete response: Change from baseline to all assessment time points*
Proportion of non-response (symptom reocurrence after study-drug dis-continuation): Time to onset of reoccurring symptoms from V25 to V26
Safety of subjects treated with avdoralimab: Any time from the first treatment administration

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

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

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

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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 trial is defined as last patient, last visit.

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:

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.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)

routine care

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-12-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-10

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-07-07

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