Clinical Trials Register

Summary
EudraCT Number:	2013-004726-28
Sponsor's Protocol Code Number:	ILIT2Linköping-Jönköping
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-11-27
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

Sweden - MPA

A.2

EudraCT number

2013-004726-28

A.3

Full title of the trial

Double-blind randomised controlled study to down regulate allergic responses in adults with allergic rhinoconjunctivitis by using three intralymphatic injections of grass and/or birch allergen one month in between during the non-seasonal period.

Dubbelblind randomiserad kontrollerad studie avseende nedreglering av allergisvar hos vuxna med allergisk rinokonjunktivit genom att använda tre intralymfatiska injektioner av gräs- och/eller björkallergen med en månads mellanrum under icke-pollenperiod.

A.3.1

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

A treatment study of 66 adult persons with injection of grass- and/or birch pollen in a lymph nodule with one month in between - for treatment of pollen allergy.

Behandling av 66 vuxna som har pollenallergi med tre injektioner av gräs- och/eller björkallergen i en lymfkörtel med en månads mellanrum.

A.3.2

Name or abbreviated title of the trial where available

ILIT2 - trial to down regulate allergy by IntraLymphatic allergen ImmunoTherapy

ILIT2 - studie för att nedreglera allergi med IntraLymfatisk ImmunTerapi

A.4.1

Sponsor's protocol code number

ILIT2Linköping-Jönköping

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	Allergy Centre
B.1.3.4	Country	Sweden
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	FORSS foundation
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Allergy Centre
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	Allergy Centre
B.5.2	Functional name of contact point	Lennart Nilsson
B.5.3	Address:
B.5.3.1	Street Address	Allergy Centre/University Hospital
B.5.3.2	Town/ city	Linköping
B.5.3.3	Post code	58185
B.5.3.4	Country	Sweden
B.5.4	Telephone number	0046101034781
B.5.5	Fax number	0046101034773
B.5.6	E-mail	Lennart.J.Nilsson@lio.se

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	ALK-Alutard SQ Betula verrucosa (R)
D.2.1.1.2	Name of the Marketing Authorisation holder	ALK-Abello
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	ALK-Alutard SQ Betula verrucosa (R)
D.3.2	Product code	VO1AA05
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intralymphatic use
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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	ALK-alutard SQ 5-grasses
D.2.1.1.2	Name of the Marketing Authorisation holder	ALK-Abello
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	ALK-alutard SQ 5-grasses
D.3.2	Product code	VO1AA02
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intralymphatic use
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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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	Injection
D.8.4	Route of administration of the placebo	Intralymphatic use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Allergic rhinoconjunctivitis

Allergisk rinokonjunktivit

E.1.1.1

Medical condition in easily understood language

Hay fever

Pollensnuva

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Symptoms and medicine consumption via "Rhinoconjunctivitis Total Symptom Score" (RTSS) and use of rhinitis medications (MS) will be evaluated during the season before treatment and compared with the three following pollen seasons. The RTSS and medication score will be answered by the patients at the end of the birch pollen season and at the end of the grass pollen season.

Symtom och medicinkonsumtion via "Rhinoconjunctivitis Total Symptom Score" och användande av allergimediciner (MS) vilket utvärderas under pollensäsongen innan behandlingen och under de tre följande pollensäsongerna. RTSS och medicin-användande utvärderas i slutet av björkpollensäsongen och i slutet av gräspollensäsongen.

E.2.2

Secondary objectives of the trial

Symptoms following conjunctival allergen provocation before treatment compared to two months after the end of the first and third season after treatment.

Effects on quality of life (QoL), measured for the season before the treatment and after the three following pollen seasons using the "Rhinoconjunctivitis Quality of Life Questionnaire" (RQLQ).

Skin prick reactions, specific IgE, inflammatory mediators and cell-mediated immunity in blood after the first and third pollen seasons after treatment compared with pretreatment.

Safety variables: Registration of adverse events from the time of the first injection to 1 year after the last injection has been given to all patients. Also, control of Hb, leucocytes, differential count of leucocytes, transaminases and creatinine will be done before the treatment, after the treatment and at the end of the study.

Symtom vid konjunktival allergenprovokation före behandling jämfört med två månader efter slutet av den första och tredje pollensäsongen efter behandling.

Effekt på livskvalitet (QoL), mätt säsongen före behandling och efter de tre följande pollensäsongerna genom att använda "Rhinoconjunctivitis Quality of Life Questionnaire" (RQLQ).

Pricktestreaktioner, analys av specifikt IgE, inflammatoriska mediatorer samt cellmedierad immunitet efter den första och tredje pollensäsongen efter behandling jämfört med innan behandling.

Säkerhetsvariabler: Registrering av oväntade händelser från tiden av första injektionen till ett år efter sista injektionen har givits till alla patienterna. Dessutom, kontroll av Hb, vita, diff, transaminaser och kreatinin görs innan behandling, efter behandling och vid slutet av studien.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age 18-55 years,
Seasonal allergic symptoms for grass and birch during the two latest seasons
Positive skin prick test to birch and grass.
Retrospective symptoms measured as RTSS >= 8
Accepted and signed informed consent.

18-55 års ålder.
Allergiska pollensymtom för gräs och björk under de senaste två pollensäsongerna.
Positiv pricktest mot björk och gräs.
Retrospektiva symtom mätta med RTSS på mer än eller lika med 8.
Underskrivet informerat samtycke

E.4

Principal exclusion criteria

The presence of any of the following will exclude the potential study patient from entry into the study and will exclude the patient for the ILIT injections at visits 3, 4 and 5:

Pregnancy or nursing, or planning for that November 2014 until mars 2015. Women with childbearing potential should use contraceptives. Condom only is not enough as contraceptive.
Adequate anticonception:
- Oral contraceptive, either combined or progestogen alone,
- Injectable progestogen,
- Implants or etenogestrel or levonogestrel,
- Sterilisation done by the fertile woman, or male partner sterilization prior to the female subject’s entry into the study, and this male is the sole partner for that subject.
a. Also, has practiced adequate contraception for 30 days prior to the first ILIT injection
b. Has a negative pregnancy test on the day of vaccination
c. Has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series.
Autoimmune or collagen disease
Known cardiovascular disease, i.e. not even NYHA class I.
ACE-blockers withdrawn after discussion with the Principal Investigator 2 weeks before first injection until 2 weeks after last injection
Pulmonary disease with FEV1 < 80 % of predicted
Pulmonary disease, perennial or seasonal with daily use of more than 800 microgram inhalated budesonide/ day (or equivalent) or treatment with omalizumab.
Unstable asthma, decided by the investigator or >15% reversibility in FEV1 in visit 2.
Concomitant infection with fever or other signs/symptoms of an acute or chronic infection vid behandling.
Allergic reaction last 3-4 days or anaphylaxia last month before ILIT injections.
Vaccination of any kind one month before to one month after the three times of ILIT injections.
Recent or on-going hepatic disease
Recent or on-going renal disease
All tumour diseases without non-melanoma skin cancers or in situ cervix cancer
Increased bleeding tendency with or without abnormal platelets, PK-INR or APTT.
Any other than study medication with an effect of interfering with the immune response
Immuno- or chemotherapy last 15 years
Upper airway disease (non-allergic sinusitis, nasal polyps)
Depot steroid injection for treatment of allergic rhinoconjunctivitis
Chronic obstructive or restrictive lung disease
Disease or conditions rendering the treatment of anaphylactic reactions difficult (symptomatic coronary heart diseases, severe arterial hypertension and treatment with beta-blockers)
Major metabolic disease
Known or suspected allergy to additives to the study product
Skin diseases with barrier defect in the inguinal areas
Alcohol, drug abuse or tobacco smoking
Mental incapability of coping with the study
Participation in another clinical study from visit one until last patient has been evaluated after the pollen season after treatment. Thereafter, studies with pharmacological agents or studies that could otherwise disturb the study are not permitted after the first evaluation of the study.

Om något av följande föreligger exkluderas patienten ur studien och patienten exkluderas från ILIT-injektioner vid besök 3, 4 och 5:
Graviditet eller amning, eller planerande för graviditet under perioden November 2014 - Mars 2015. Kvinnor i fertil ålder skall använda antikonceptionsmedel. Kondom är inte tillfyllest som antikonceptionsmedel.
Adekvat antikonception:
- Oralt preventivmedel, antingen kombinationspreparat eller progesteron
- Injicerat progesteron
- Implantat för antikonception
- Sterilisering av den fertila kvinnan, eller dennas manliga partner om denne har steriliserat sig innan studien och är den ende sexuella partnern för kvinnan
a, Dessutom om kvinnan har använt adekvat kontraception i 30 dagar innan den första ILIT-injektionen
b, Har en negativ graviditetstest på dagen för vaccination
c, Har godkänt att fortsätta adekvat kontraception under hela behandlingsperioden och i två månader efter avslutad vaccinatiosserie
Autoimmun eller kollagen sjukdom.
Känd kardiovaskulär sjukdom, vilket innebär uteslutande även av HYHA klass I.
ACE-hämmare, efter diskussion med prövningsledare, 2 veckor före första injektionen till 2 veckor efter sista injektionen
Lungsjukdom med FEV1 <80% av förväntat
Lungsjukdom, perenn eller under säsongs, med dagligt användande av >800 mikrogram inhalerat budesonid/dag (eller ekvivalent dos) eller behandling med omalizumab
Instabil astma, beslutat av prövningsledare, eller >15% reversibilitet i FEV1 vid besök 2.
Samtidig infektion med feber eller andra tecken/symtom av en akut eller kronisk infektion vid behandling
Allergisk reaktion senaste 3-4 dagarna eller anafylaxi senaste månaden innan ILIT-injektionerna
Vaccination av ngt vaccin en månad före till en månad efter de tre gångerna som ILIT-injektioner ges
Nylig eller pågående leversjukdom
Nylig eller pågående njursjukdom
Alla tumörsjukdomar förutom icke-melanoma hudmaligniteter eller in situ cervixcancer
Ökad blödningstendens med eller utan abnormala trombocyter, PK-INR eller APTT
Någon annan än studiemedicinen med en effekt som interferar med immunsvar
Immun- eller kemoterapi senaste 15 åren
Övre luftvägssjukdom (icke-allergisk sinuit, nasal polyp)
Depot steroidinjektion för behandling av allergisk rinokonjunktivit
Kronisk obstruktiv eller restriktiv lungsjukdom
Sjukdom eller förhållande som kan påverka behandlingen av anafylaktisk reaktion (symptomatisk koronarkärlssjukdom, svår arteriell hypertension och behandling med betablockerare
Metabolisk sjukdom av allvarligare grad
Känd eller misstänkt allergi mot tillsatser i studieprodukten
Hudsjukdomar med barriärdefekt i ljumskområdena
Alkohol eller drogmissbruk
Mental oförmåga att kunna medverka i studien
Deltagande i någon annan klinisk studie från besök 1 till sista patient har evaluerats efter pollensäsongen efter studiebehandling. Studie med läkemedel eller studier som på annat vis skulle kunna störa studien är inte heller tillåtna efter den första evalueringen av studien.

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

See above

Se ovan

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

see above

Se ovan

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

Yes

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)

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

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

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

Last visit for last patient

Sista besöket för sista patienten

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)

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 according to general pracitice

Rutinomhändertagande enligt gängse praxis

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

2014-01-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-12-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-11-16

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