ICH GCP - EU Clinical trials Registry - 2018-003199-10 (DE)

Prove cliniche Nct

Summary
EudraCT Number:	2018-003199-10
Sponsor's Protocol Code Number:	OLE-NLRC4/XIAP.2016.001
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:	2018-10-04
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

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2018-003199-10

A.3

Full title of the trial

Open-label extension study with Tadekinig alfa (r-hIL-18BP) to monitor safety and tolerability in patients with IL-18 driven monogenic autoinflammatory conditions: NLRC4 mutation and XIAP deficiency

A.3.1

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

OPEN-LABEL STUDY: THERAPEUTIC USE OF TADEKINIG ALFA IN NLRC4 MUTATION AND XIAP DEFICIENCY

A.4.1

Sponsor's protocol code number

OLE-NLRC4/XIAP.2016.001

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	AB2 Bio Ltd.
B.1.3.4	Country	Switzerland
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	AB2 Bio Ltd.
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AB2 Bio Ltd.
B.5.2	Functional name of contact point	Eduardo Schiffrin
B.5.3	Address:
B.5.3.1	Street Address	innovation Park Buildling B
B.5.3.2	Town/ city	Lausanne
B.5.3.3	Post code	1015
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	0041216940043
B.5.6	E-mail	Eduardo.Schiffrin@ab2bio.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	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/150/16
D.3 Description of the IMP
D.3.1	Product name	Tadekinig alfa
D.3.2	Product code	r-hIL-18BP
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Yes
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	Tadekinig alfa
D.3.9.1	CAS number	220712-29-8
D.3.9.2	Current sponsor code	r-hIL-18BPa
D.3.9.3	Other descriptive name	TADEKINIG ALFA
D.3.9.4	EV Substance Code	SUB180338
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	85
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

NLRC4 mutation
XIAP deficiency

E.1.1.1

Medical condition in easily understood language

NLRC4 mutation
XIAP deficiency

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

This is an open-label extension study for patients previously enrolled in the preceding clinical trial NLRC4/XIAP.2016.001 (IND N° 127953 _ EudraCT number: 2018-003297-27) to evaluate the long-term safety and tolerability of TA in patients suffering from pediatric monogenic autoinflammatory diseases harboring deleterious mutations of NLRC4 and XIAP

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Patients have participated in the preceding clinical trial NLRC4/XIAP.2016.001 (IND N° 127953 _ EudraCT number: 2018-003297-27) by one of the following mechanisms:
a.Patients that have completed the first 18-week RCT phase of the preceding clinical trial but were not eligible for the RW phase due to flare symptoms.
b.Patients that completed the first 18-week RCT phase and completed the RW phase of the preceding clinical trial.
c.Patients who have exited either the RCT or RW phase of the preceding clinical trial due to treatment failure requiring rescue immunosuppression. Such patients must wait a minimum of 4 weeks after treatment discontinuation from the preceding clinical trial before enrolling in this OLE. If patients do not consent to enroll in the OLE after their early termination in the main study, they will be asked to continue with the planned visits of the main study.
The time period between participation in the RCT or RW and the OLE study should not exceed 3 months. After this period, patients are no longer eligible for enrollment into the OLE study.
2.Women of childbearing potential with negative urine pregnancy test (UPT) at all visits (if UPT is positive, a blood test for human chorionic gonadotropin (hCG) is to be performed) and who agree to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment. Birth control methods considered highly effective are: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner or sexual abstinence. In each case of delayed menstrual period (over one month between menstruations, confirmation of absence of pregnancy is strongly recommended. This recommendation also applies to women of childbearing potential with infrequent or irregular menstrual cycles. A post-study contraception duration of 4 weeks is recommended taking into account the median half-life of Tadekinig alfa of almost 40h and 5 half-lives representing a duration of 200 hours

E.4

Principal exclusion criteria

1.Patients may not enter the OLE if they voluntarily withdrew from RCT or RW study or if the time period between participation exceeds 3 months
2.Evidence or history of malignancy
3.Evidence of invasive or life-threatening infection
4.History of tuberculosis
5.Life-threatening bleeding within 2 weeks of screening
6.Vaccination with a live vaccine within the previous 3 months
7.Evidence of severe organ compromise including but not limited to:
Intractable encephalopathy, psychosis, or seizures
Creatinine of > 2X ULN (patients receiving dialysis are also excluded)
Albumin < 1.5 g/dL, ALT>10x ULN, or evidence of acute liver failure
Mechanical ventilation (including invasive and non-invasive forms)
Heart failure requiring medical support including medications
Hypotension from any cause requiring the use of vasopressors
8.Pregnant or breastfeeding females
9.Inability to follow highly effective birth control recommendations during the study and until 1 month after the end of the treatment.
10.Inability to provide informed consent, and also assent if applicable
11.Life expectancy less than 4 weeks
12.Concomitant use of other immunosuppression except NSAIDs, glucocorticoids, cyclosporine, tacrolimus, IL-1 inhibitors (Anakinra, Canakinumab, or Rilonacept)
13. Hypersensitivity to the active substance or one of the excipients of the investigational product

E.5 End points

E.5.1

Primary end point(s)

- Reports of adverse events: The incidence, nature and severity of AEs will be reported. Reports will be produced according to the MedDRA highest hierarchy / System Organ Class, by MedDRA Preferred Term, by relationship to Tadekinig alfa and by Common Terminology Criteria for Adverse Events (CTCAE)/severity.
- Abnormal physical examination: body temperature, hepatosplenomegaly, and presence of skin rash.
- Abnormal Laboratory results:
Including CRP, ferritin, fibrinogen, D-dimer, and any clinically significant abnormal laboratory results. All clinically significant abnormal laboratory results or assessments must be followed until they resolve (return to normal or baseline values) or stabilize, or until they are judged by the Investigator to be no longer clinically significant.
- Immunogenicity evaluation: Generation of anti-recombinant human Interleukin-18 Binding Protein (anti-rhIL-18BP) antibodies
- Local tolerability at the injection site (evaluated by a standardized assessment)

E.5.1.1

Timepoint(s) of evaluation of this end point

26 weeks

E.5.2

Secondary end point(s)

Not applicable

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable

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

E.6.6

Pharmacokinetic

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)

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

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

Canada

Germany

United States

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 OLE trial will be defined as the date of the database lock

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

Yes

F.1.1

Number of subjects for this age range:

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.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

In this case, the informed consent will be signed by the legal gardian

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

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

2019-03-26

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status

Prove cliniche Nct

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici