Clinical Trials Register

Summary
EudraCT Number:	2018-004869-14
Sponsor's Protocol Code Number:	CLL19H1
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-02-07
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2018-004869-14

A.3

Full title of the trial

Peptide vaccination with PD-L1 and PD-L2 peptides in untreated chronic lymphatic leukemia.

Peptidvaccination med PD-L1 og PD-L2 peptider til patienter med ubehandlet kronisk lymfatisk leukæmi

A.3.1

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

Vaccination therapy for patients with untreated chronic lymphocytic leukemia

Terapeutisk vaccinationsbehandling til patienter med ubehandlet kronisk lymfatisk leukæmi

A.4.1

Sponsor's protocol code number

CLL19H1

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	Dept. of hematology, Herlev Hospital
B.1.3.4	Country	Denmark
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	IO Biotech
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dept. of hematology, Herlev Hospital
B.5.2	Functional name of contact point	Primary invetsigator
B.5.3	Address:
B.5.3.1	Street Address	Herlev ringvej 75
B.5.3.2	Town/ city	Herlev
B.5.3.3	Post code	2730
B.5.3.4	Country	Denmark
B.5.4	Telephone number	004538689210
B.5.6	E-mail	uffe.klausen@regionh.dk

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	PD-L1 Long1 and PDL2 Long201
D.3.4	Pharmaceutical form	Concentrate 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	PD-L1 long1 (9-28)
D.3.9.2	Current sponsor code	PD-L1 long1
D.3.9.3	Other descriptive name	PEPTIDE ANTIGENS
D.3.9.4	EV Substance Code	SUB169176
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PD-L2 Long201
D.3.9.3	Other descriptive name	PEPTIDE ANTIGENS
D.3.9.4	EV Substance Code	SUB169176
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Montanide ISA51
D.3.9.1	CAS number	190396-06-6
D.3.9.3	Other descriptive name	MONTANIDE ISA51
D.3.9.4	EV Substance Code	SUB33722
D.3.10	Strength
D.3.10.1	Concentration unit	µl microlitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic lymphocytic leukemia with un-mutated IGHV

kronisk lymfatisk leukæmi med umuteret IGHV

E.1.1.1

Medical condition in easily understood language

chronic lymphocytic leukemia with adverse prognostic gene variation

Kronisk lymfatisk leukæmi med dårlig prognostisk genvariation

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

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	10008958
E.1.2	Term	Chronic lymphocytic leukaemia
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 main objective is to evaluate the efficacy of the vaccine, in means of changes in the lymphocyte count and structural changes in lymph node and/or spleen size.

Hovedformålet er at vurderer vaccinens anti-leukæmiske effect ved at måle ændringerne I lymfocyttallet og størrelsen på sygdomsinfiltrede organer.

E.2.2

Secondary objectives of the trial

The secondary objective is to evaluate vaccine specific immune
responses before and during the treatment and continue to follow the safety profile of the drug.

Det sekundære mål er at evaluere vaccinespecifikke immunresponser før
og under behandlingen, samt fortsætte med at registrere behandlingens bivirkninger.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

CLL according to national guidelines.
Unmutated IGHV gene
No prior CLL directed treatment
Age ≥ 18
ECOG performance status of 0 or 1
No life-threatening conditions
Adequate hematologic and end-organ function
Bone marrow function: Neutrophilocytes > 1,0 x 109/l; Platelets > 100 x 109/l
Renal function: eGFR/1,73m^2 > 50
For fertile women: agreement to use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 120 days after the last treatment.
For men: agreement to use contraceptive measures and agreement to refrain from donating sperm.

CLL ifølge nationale kriterier
Umuteret IGHV genstatus
Ingen tidligere CLL behandling
Alder ≥ 18
ECOG performance status på 0 eller 1
Ingen livstruende lidelser
Tilstrækkelig funktion af knoglemarv og øvrige vitale organer
For fertile kvinder: aftale om at anvende præventionsmetoder med en fejlfrekvens på <1% pr. År i behandlingsperioden og i mindst 120 dage efter den sidste behandling.
For mænd: Enighed om at bruge præventionsforanstaltninger og aftale om at afstå fra at give sæd.

E.4

Principal exclusion criteria

Other active malignant diseases requiring treatment.
Significant medical condition per investigators judgement e.g. severe Astma/COLD, poorly regulated heart condition, insulin dependent diabetes mellitus.
Acute or chronic viral/bacterial infection e.g. HIV, CMV, EBV, hepatitis or tuberculosis
Serious known allergies or earlier anaphylactic reactions.
Known sensibility towards Montanide ISA-51
Any active autoimmune diseases e.g. autoimmune neutropenia, thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, autoimmune glomerulonephritis, autoimmune adrenal deficiency, autoimmune thyroiditis etc.
Pregnant and breastfeeding women.
Fertile women not using secure contraception with a failure rate less than < 1%
Psychiatric disorders that according to the investigator could influence compliance.
Treatment with other experimental drugs

Andre aktive kræftsygdomme som kræver behandling, undtagen spinocellulært eller basocelulært carcinom i huden.
Betydelig medicinsk tilstand eks. Svær astma/KOL, dårligt reguleret hjerte tilstand og/eller insulinafhængig diabetes mellitus.
Akut eller kronisk viral/bakteriel infektion, f.eks. HIV, CMV, EBV, hepatitis eller tuberkulose
Kendte allergier eller tidligere anafylaktiske reaktioner.
Kend følsomhed over for Montanide ISA-51
Aktive autoimmune sygdomme, f.eks. Autoimmun neutropeni, trombocytopeni eller hæmolytisk anæmi, systemisk lupus erythematosus, sclerodermi, myasthenia gravis, autoimmun glomerulonefritis, autoimmun binyrebarkinsuficiens, autoimmun thyroiditis etc.
Gravide og ammende kvinder
Fertile kvinder, der ikke bruger sikker prævention, med en fejlfrekvens mindre end <1%
Patienter, der tager immunsuppressive medikamenter inkl. Kortikosteroider og methotrexat
Psykiatriske lidelser, som ifølge efterforskeren kunne påvirke kompliance.
Behandling med andre eksperimentelle lægemidler

E.5 End points

E.5.1

Primary end point(s)

Responses to the vaccine according to IW-CLL response criteria

Respons til vaccinen ifølge IW-CLL responskriterier.

E.5.1.1

Timepoint(s) of evaluation of this end point

Disease assesment will be performed before and after treatment which ends after 23 weeks.

Sygdomsbyrden bliver evalueret før og efter behandlingen som afsluttes efter 23 uger.

E.5.2

Secondary end point(s)

Time to first treatment

tiden til første behandling

E.5.2.1

Timepoint(s) of evaluation of this end point

Patients will be followed until they fulfill the treatment criteria according to IW-CLL guidelines or until this endpoint can no longer be obtained.

Patienterne vil blive fulgt indtil de opfylder behandlingskriterierne ifølge IW-CLL retningslinjerne eller indtil dette endepunkt ikke længere kan opnås.

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

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.8.3

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

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 trial is LVLS

Studiet slutter ved sidste patients sidste besøg

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)

Watch and wait according to IWCLL guidelines

Kontroller uden behandling jf. IWCLL retningslinjerne

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

2019-03-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-04-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-03-08

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials