Clinical Trials Register

Summary
EudraCT Number:	2017-002106-13
Sponsor's Protocol Code Number:	ATH3G10-005
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:	2017-06-30
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

Sweden - MPA

A.2

EudraCT number

2017-002106-13

A.3

Full title of the trial

Double-blind, randomised, placebo-controlled, multicentre, Phase IIa study to investigate the effect of phosphorylcholine human monoclonal antibody (PC-mAb) 3G10 on arterial inflammation, together with safety and tolerability, in subjects with elevated lipoprotein a (Lp[a])

A.3.1

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

Double-blinded, randomised, placebo-controlled, multicentre , Phase IIa study to investigate the effect efficacy, safety and tolerability of phosphorylcholine human monoclonal antibody (PC-mAb) 3G10 on arterial inflammation, together with safety and tolerability, in subjects with elevated lipoprotein a (Lp[a ])

En fas 2a, dubbelblind, randomiserad, placebokontrollerad multicenterstudie för att undersöka effekt, säkerhet och tolerabilitet av behandling med 3G10 på arteriell inflammation hos forskningspersoner med förhöjda nivåer av lipoprotein a (Lp[a]).

A.4.1

Sponsor's protocol code number

ATH3G10-005

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	Athera Biotechnologies AB
B.1.3.4	Country	Sweden
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	Athera Biotechnologies AB
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	Athera Biotechnologies AB
B.5.2	Functional name of contact point	CEO
B.5.3	Address:
B.5.3.1	Street Address	c/o Business Center, Level 4, S:t Eriksgatan 117
B.5.3.2	Town/ city	Stockholm
B.5.3.3	Post code	SE-11343
B.5.3.4	Country	Sweden
B.5.4	Telephone number	0046761938190
B.5.6	E-mail	c.schmidt@athera.se

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	3G10
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	3G10
D.3.9.2	Current sponsor code	3G10
D.3.9.3	Other descriptive name	3G10
D.3.9.4	EV Substance Code	SUB175106
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	20
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 infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Arterial inflammation in subjects with elevated lipoprotein a (Lp[a])

E.1.1.1

Medical condition in easily understood language

Arterial inflammation in subjects with elevated lipoprotein a (Lp[a])

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10051615
E.1.2	Term	Atherosclerotic cardiovascular disease
E.1.2	System Organ Class	100000022953

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 effects of four 250 mg 3G10 once monthly intravenous injections on monocyte function ex vivo.

E.2.2

Secondary objectives of the trial

Primary objective
The primary objective is to assess the effects of four 250 mg 3G10 once monthly intravenous injections on monocyte function ex vivo.
Secondary objectives
To assess functional effects of 3G10 on arterial inflammation in vivo
To assess 3G10 effects on arterial stiffness
To assess the safety and tolerability of 3G10
Exploratory objectives
To assess the effects of 3G10 on heart function and LFR in a subgroup of the study population
To study the pharmacodynamics of 3G10 by scavenger receptor and adhesion molecule expression on circulating monocytes and other circulating biomarkers
To study the pharmacokinetics of 3G10
To further assess 3G10 effects on arterial stiffness over time
To further assess functional effects of 3G10 on arterial inflammation in vivo
To study the change in plasma protein patterns

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provision of a signed written informed consent
2. Lp(a) above 50 mg/dL at screening
3. Male or female, ≥ 50 years of age at screening
4. Weight of at least 63 kg and maximum 125 kg at screening (dose = 2-4 mg/kg body weight)

E.4

Principal exclusion criteria

1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the result or the subject’s ability to participate in the study
2. Illness (including common colds) for the last 4 weeks before Visit 3 and Visit 4
3. Medical history of myocardial infarction (MI) or stroke within 12 months of screening
4. Ongoing or paroxysmal atrial fibrillation
5. Clinically overt heart failure
6. Hypertension defined as ≥180/100 mmHg
7. Diabetes mellitus
8. Ongoing treatment with statins or PCSK9 inhibitor
Except when:
• Statin is prescribed for primary prevention and Lp(a) >50 mg/dl and LDLc >100 mg/dL (2.5 mmol/L)
• Statin and/or PCSK9, or other lipid lowering medication, are prescribed for secondary prevention, and Lp(a) >50 mg/dL
9. Systemic autoimmune diseases requiring treatment
10. Cancer, excluding basal cell carcinoma, within the last five years
11. Medical PET, SPECT, abdominal or thoracic CT examination during the previous 12 months’ time period
12. Conditions contraindicating MRI such as, but not limited to, claustrophobia, having a history of brain or heart surgery and pacemaker implantation, permanent make-up, past or present occupation as metalworker or welder. Having metallic implants that cannot be declared safe under the employed MRI scanning conditions, or which will significantly degrade MRI scan quality.
13. Positive HIV or hepatitis test
14. Clinically significant abnormal findings in haematology or clinical chemistry at screening or any value ≥ 3 times the upper limit of normal haematology or clinical chemistry at screening
15. The subject is unable to understand the written and verbal instructions
16. Pregnant or breast feeding women. A negative urine pregnancy test must be demonstrated in females at screening. The females must be of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal defined as 12 month of amenorrhea (in questionable cases a blood sample with simultaneous determination of follicle stimulating hormone 25 150 IE/L and estradiol <200 pmol/L is confirmatory). The male subjects must agree to use condom in combination with use of contraceptive methods with failure rate of <1% to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the date of dosing until 3 months after last dosing of the IMP.
17. History or current drug or alcohol abuse which in the opinion of the Investigator should preclude participation in the study
18. Subjects who have participated in any other clinical study that included drug treatment within 3 months of the administration of investigational product in this study
19. Subjects who have received any type of vaccination within 21 days before dosing or who anticipate the need for vaccination before the end of the study
20. Plasma donation within one month of screening or any blood donation/blood loss >450 mL during 3 months prior to screening
21. Subjects who have planned any scheduled invasive treatment/surgical procedure during the whole study
22. Investigator considers subject unlikely to comply with study procedures, restrictions and requirements
23. History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses.
24. Recent (<1 month prior to screening) or current treatment with medications that may have a significant effect on plaque inflammation, including oral, rectal, or subcutaneous/intramuscular injected corticosteroids and immunosuppressive medications (e.g. cyclosporine, methotrexate, tacrolimus, azathioprine, anti-thymocyte globulin, sirolimus, anti-TNF agents such as infliximab, anti-IL6 therapy such as tocilizumab, or anti-IL1 therapy such as anakinra)

E.5 End points

E.5.1

Primary end point(s)

Change in TEM in monocytes isolated from treated subjects from baseline to visit 11

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to visit 11

E.5.2

Secondary end point(s)

Secondary efficacy endpoints
Change in TBRmax in common carotid arteries by fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) from baseline to Visit 11
Change in PWV (m/sec) assessed by Sphygmocor Xcel from baseline to Visit 11

Safety endpoints
Safety and tolerability: AEs/SAEs, vital signs, physical examination, ECG and laboratory assessments including haematology, clinical chemistry and immunogenicity

Exploratory endpoints
Change from baseline in cardiac variables and LFR variables, as assessed by MRI, in a subgroup of the study population
IgM anti-PC level, other circulating biomarkers, monocyte adhesion markers and scavenger receptors assessed by fluorescence-activated cell sorting (FACS) over time
Pharmacokinetics: 3G10 serum levels
Arterial stiffness variables, assessed by Sphygmocor Xcel
TBRmean (carotid and aorta), TBRgluc (carotid and aorta) and TBRmax (aorta) assessed by 18F-FDG PET/CT
Change in protein pattern from baseline to Visit 11 as assessed by proteomics measurements

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary efficacy endpoints are evaluated from baseline to Visit 11

Safety endpoints: Adverse events (AE) will be assessed from administration of study drug until end of study visit. ECG will be assessed at screening and pre-dose as well as post dose at dosing visits. Vital signs and physical examination will be assessed during all visits to the clinic. Safety blood samples will be assessed at all visit to the clinic. Immunogenicity will be assessed pre-dose at each dosing visit dosing and at the end of study visit.

Exploratory endpoints will be presented showing observed values and changes from baseline at each available visit/assessment

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

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Last visit of the last subject in the trial

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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.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

2017-09-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-07-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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