Clinical Trials Register

Summary
EudraCT Number:	2020-003966-38
Sponsor's Protocol Code Number:	CADPT06A12201
National Competent Authority:	Iceland - IMCA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2024-03-06
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

Iceland - IMCA

A.2

EudraCT number

2020-003966-38

A.3

Full title of the trial

EXploratory PLatform trial on Anti-INflammatory agents in Alzheimer’s Disease (EXPLAIN-AD): A randomized, placebo controlled, multicenter platform study to evaluate the efficacy, safety, tolerability and pharmacokinetics of various anti-inflammatory agents in patients with mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease

A.3.1

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

Study of the efficacy and safety of various anti-inflammatory agents in participants with mild cognitive impairment or mild Alzheimer's Disease

A.3.2

Name or abbreviated title of the trial where available

EXploratory PLatform trial on Anti-INflammatory agents in Alzheimer’s Disease (EXPLAIN-AD)

A.4.1

Sponsor's protocol code number

CADPT06A12201

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	Novartis Pharma AG
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	Novartis Pharma AG
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	Novartis healthcare A/S
B.5.2	Functional name of contact point	Medical information
B.5.3	Address:
B.5.3.1	Street Address	Edvard Thomsens Vej 14
B.5.3.2	Town/ city	Kopenhagen S
B.5.3.3	Post code	2300
B.5.3.4	Country	Denmark
B.5.4	Telephone number	-
B.5.5	Fax number	-
B.5.6	E-mail	skriv.til@novartis.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	Yes
D.2.1.1.1	Trade name	Ilaris
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Canakinumab
D.3.2	Product code	ACZ885
D.3.4	Pharmaceutical form	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	CANAKINUMAB
D.3.9.1	CAS number	914613-48-2
D.3.9.2	Current sponsor code	ACZ885
D.3.9.4	EV Substance Code	SUB30137
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	150
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

Mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease

E.1.1.1

Medical condition in easily understood language

Study to evaluate the efficacy, safety, tolerability and pharmacokinetics of various anti-inflammatory agents in patients with early Alzheimer's disease

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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	10001896
E.1.2	Term	Alzheimer's disease
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To compare the effects of each individual agent vs. placebo on cognition in early AD

E.2.2

Secondary objectives of the trial

• To investigate the safety (AEs) and tolerability of each individual agent vs placebo
• To investigate the effects of each individual agent vs placebo in lowering central inflammation
• To explore the effects of each individual agent vs placebo on neuropsychiatric symptoms
• To compare the effects of each individual agent vs placebo on function (activities of daily living)
• To compare the effects of each individual agent vs placebo on memory and executive function
• To determine the pharmacokinetics of each individual agent
• To determine the total target and immunogenicity of each individual biotherapeutic agent

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female, age ≥ 45 years and ≤ 90 years at the time of signing the informed consent;
2. Participant has a reliable study partner or caregiver can accompany the participant to all visits;
3. A diagnosis of probable MCI due to AD or mild AD according to the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria;
4. Confirmed amyloid and tau positivity via CSF sampling performed at screening;
5. Mini-Mental State Examination (MMSE) total score of 20 to 30 (inclusive) and DSST score at least one standard deviation (SD) below normative data at point of screening.

E.4

Principal exclusion criteria

1. Use of other investigational agents prior to screening until:a) Small molecules: after five half-lives, or within 30 days until the expected pharmacodynamic effect has returned to baseline, whichever is longer; OR b) Biologicals: blood concentration has returned to baseline (or below serological responder threshold) for antibodies induced by active immunotherapy; or five half-lives for monoclonal antibodies or other biologicals;
2. Current medical or neurological condition that might impact cognition or performance on cognitive assessments, e.g., MCI not due to AD, non-Alzheimer dementia, Huntington’s disease, Parkinson’s disease, stroke, schizophrenia, bipolar disorder, active major depression, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), active seizure disorder, or history of traumatic brain injury associated with loss of consciousness and ongoing residual transient or permanent neurological signs/symptoms including cognitive deficits, and/or associated with skull fracture;
3. If a historical MRI or CT scan has been performed, signs of major cerebrovascular disease shown on such scans (i.e., presence of infarction in greater than 25% of white matter; more than one lacune within basal ganglia or more than 2 lacunes in white matter);
4. Diagnosis of vascular dementia prior to screening (e.g.., modified Hachinski Ischaemic Scale score > 6 or those who meet the NINDS AIREN criteria for vascular dementia);
5. Previous exposure to amyloid vaccines or intravenous immunoglobulins meant to treat Alzheimer's disease.

E.5 End points

E.5.1

Primary end point(s)

• The Neuropsychological Test Battery (NTB) score

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks

E.5.2

Secondary end point(s)

• Safety
• Positron-Emission Tomography Translocator Protein 18 kDa (PET TSPO)
• The Neuropsychiatric Inventory (NPI-D) total score
• Tablet-based neuropsychiatric At-Home study partner assessment score
• The Everyday Cognition (ECog) scale
• The Neuropsychological Test Battery memory and executive function composites
• Digit Symbol Substitution Test
• Tablet-based cognitive at-home assessment
• Pharmacokinetics and pharmacodynamics in plasma and cerebrospinal fluid

E.5.2.1

Timepoint(s) of evaluation of this end point

throughout the 24 week trial

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity and Tolerability

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

Yes

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

Yes

E.8.2.3.1

Comparator description

Platform study

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

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

United Kingdom

United States

Finland

Iceland

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

LVLS

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

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:

180

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

720

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

If a participant’s capacity to consent is impaired his/her representative may consent (where allowed). The study is explained to the extent possible and participants (if capable) must indicate agreement with signed consent.

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

560

F.4.2.2

In the whole clinical trial

900

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)

Following the completion of the study, no further study treatment will be made available to patients. Patients will be advised to follow the recommended standard of care as per local guidelines as directed by their 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

2021-06-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-29

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-03-07

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