Clinical Trials Register

Summary
EudraCT Number:	2015-003369-27
Sponsor's Protocol Code Number:	REGAIN
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-05-18
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 - BfArM

A.2

EudraCT number

2015-003369-27

A.3

Full title of the trial

A Phase I-IIa trial on low-dose IL-2 (Aldesleukin) treatment for immunological dysregulation in common variable immunodeficiency (CVID)

Phase I-IIA Studie zu niedrig-dosiertem IL-2 (Aldesleukin) in der Behandlung von Immundysregulation bei variablem Immundefekt (CVID [”common variable immunodeficiency”])

A.3.1

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

A Phase I-IIa trial on low-dose IL-2 (Aldesleukin) treatment for immunological dysregulation in common variable immunodeficiency (CVID)

A.3.2

Name or abbreviated title of the trial where available

REGAIN: REGulatory T cells and Aldesleukin for Immunodeficiency- associated eNteropathy

A.4.1

Sponsor's protocol code number

REGAIN

A.5.4

Other Identifiers

Name:

DRKS

Number:

DRKS00010424

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	Universitätsklinikum Freiburg
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	University of Freiburg
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Universitätsklinikum Freiburg
B.5.2	Functional name of contact point	Leiter der Klinischen Prüfung
B.5.3	Address:
B.5.3.1	Street Address	Breisacher Straße 115
B.5.3.2	Town/ city	Freiburg
B.5.3.3	Post code	79106
B.5.3.4	Country	Germany
B.5.6	E-mail	klaus.warnatz@uniklinik-freiburg.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	Yes
D.2.1.1.1	Trade name	PROLEUKIN® S
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharma GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Aldesleukin
D.3.4	Pharmaceutical form	Powder for solution for injection/infusion
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	Aldesleukin
D.3.9.1	CAS number	110942-02-4
D.3.9.3	Other descriptive name	ALDESLEUKIN
D.3.9.4	EV Substance Code	SUB05303MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	18x10 6
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

autoimmune enteropathy (AIE) in common variable immunodeficiency (CVID).

E.1.1.1

Medical condition in easily understood language

chronic diarrhea due to autoimmune disease of the gut in patients with a primary immunodeficiency (CVID)

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	19.0
E.1.2	Level	PT
E.1.2	Classification code	10021449
E.1.2	Term	Immunodeficiency common variable
E.1.2	System Organ Class	10021428 - Immune system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10017922
E.1.2	Term	Gastroenteropathy NOS
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary objective:
To assess the safety (esp. with respect to autoimmunity) of different doses of low-dose s.c. Aldesleukin treatment in CVID patients with AIE

E.2.2

Secondary objectives of the trial

Secondary objectives:
To assess the optimal dose for expansion of Treg cells in CVID patients.
To assess the impact of low-dose Aldesleukin on chronic diarrhoea in patients with AIE and CVID.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Adult patient with a diagnosis of CVID according to the ESID criteria (www.esid.org)
Sufficient IgG replacement therapy for at least 6 months with IgG trough levels above 6g/l.
Diagnosis of autoimmune enteropathy of the upper gastrointestinal tract proven by histology. Last biopsy <6 months before study inclusion.
Clinical activity of enteropathy within the last month before inclusion defined as ≥ 3 loose stools per day on more than half of the days.
Report of negative culture for pathogenic intestinal bacteria within one month before study inclusion.
Failure of topic or systemic steroid treatment or contraindications for steroid therapy or unacceptable side effects of steroid treatment.
Daily dose of glucocorticosteroids ≤ 20mg prednisolone (or equivalent) at the day of baseline visit.

E.4

Principal exclusion criteria

Need for a scheduled application of contrast agent during the trial.
Patients with malignant neoplasm within the last 5 years prior to visit 1 (except adequately treated basal cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the uterine cervix).
Patients with an ECOG ≥ 2.
Patients with a history of or current severe cardiac or pulmonary disease or uncontrolled pericardial or pleural effusion.
Patients with thrombosis or thromboembolic event < 6 months before study inclusion.
Patients with active CNS involvement (e.g. intracranial granulomata, multiple sclerosis, vasculitis or other autoinflammatory CNS disease) or recurrent seizures.
Uncontrolled chronic infectious disease (including HIV, EBV, CMV, HCV, HBV, tuberculosis) or conditions which represent a high risk for infection (i.e. severe bronchiectasis) which might interfere with the study at the discretion of the investigator.
Major infection requiring antibiotic therapy or infection requiring hospitalization within the last 4 weeks prior to the baseline visit.
Treatment with any immunosuppressive, cytotoxic drug within the last 4 weeks prior to visit 1 (except prednisolone ≤ 20mg or equivalent).
Patients with allogenic organ transplants.
Active autoimmue manifestation requiring treatment (except autoimmune enteropathy).
Clinically relevant chronic or acute renal (creatinine >1.25 ULN), hepatic (AST > 3 ULN, bilirubin > 1.5 x ULN) or other severe organ impairment.
Preexisting cytopenia (hematocrit <30%, thrombocytes <100.000/μl, leukocytes <3.000/μl or neutrophils <1.500/μl or CD4 cell counts <100/ μl.

E.5 End points

E.5.1

Primary end point(s)

Primary safety endpoint:
Adverse events will be recorded according to GCP guidelines during the treatment and follow-up phase at every site visit (every two weeks). Patients will be clinically monitored for signs of autoimmunity at every site visit. Autoantibodies will be measured before start of the therapy and after completion of the follow-up period. Differential blood count (eosinophil counts), lymphocyte subsets as well as liver enzymes and creatinine will be measured every two weeks.

E.5.1.1

Timepoint(s) of evaluation of this end point

Data from at least 33 treatment cycles (n=3 patients fulifilling the whole treatment period) will be analysed. Regression models will be used to describe the relation of the different outcomes to dose.

E.5.2

Secondary end point(s)

Key secondary endpoint(s):
% of Tregs will be measured before each cycle and on day 4 of every cycle and on day 6 of the induction cycle(s).
Disease activity will be assessed with a self-administered questionnaire (IBDQ) and a stool diary filled in by patients.

E.5.2.1

Timepoint(s) of evaluation of this end point

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

E.6.7

Pharmacodynamic

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

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

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 clinical trial can be terminated prematurely at his centre by the investigator if, for instance unforeseeable circumstances have arisen at the trial centre which preclude the continuation of the clinical trial, the investigator considers that the resources for continuation are no longer available, the investigator considers that the continuation of the trial is no longer ethically or medically justifiable.

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

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)

After end of the trial, continuation of trial medication is at the discretion of the treating physician.

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

2016-06-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-01

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-06-05

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