Clinical Trials Register

Summary
EudraCT Number:	2019-000848-95
Sponsor's Protocol Code Number:	020119
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:	2019-02-14
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

Denmark - DHMA

A.2

EudraCT number

2019-000848-95

A.3

Full title of the trial

A Placebo-Controlled, Double-Blind, Randomized, Proof-of-Concept Study to Evaluate the Efficacy and Tolerability of Erenumab in Patients with Trigeminal Neuralgia

Et randomiseret, dobbelt-blindet, placebo-kontrolleret eksplorativt studie med hen-blik på at vurdere effekten og tolerabiliteten af erenumab til behandling af patienter med trigeminusneuralgi.

A.3.1

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

Investigation on the effect and tolerability of erenumab in trigeminal neuralgia

Undersøgelse af effekten og tolerabilitet af erenumab ved trigeminusneuralgi

A.4.1

Sponsor's protocol code number

020119

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	Dansk Hovedpine Center, Neurologisk Klinik, Rigshospitalet - Glostrup
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	Novartis
B.4.2	Country	European Union
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Danish Headache Center
B.5.2	Functional name of contact point	Lars Bendtsen
B.5.3	Address:
B.5.3.1	Street Address	Valdemar Hansens Vej 5
B.5.3.2	Town/ city	Glostrup
B.5.3.3	Post code	2600
B.5.3.4	Country	Denmark
B.5.5	Fax number	38633065
B.5.6	E-mail	lars.bendtsen@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	Yes
D.2.1.1.1	Trade name	Aimovig
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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.3.4	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	ERENUMAB
D.3.9.3	Other descriptive name	Aimovig
D.3.9.4	EV Substance Code	SUB183612
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	140
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	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	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
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

Trigeminal neuralgia

Trigeminusneuralgi

E.1.1.1

Medical condition in easily understood language

Trigeminal neuralgia is a painful neuropathic disorder characterized by stabbing, intense, touch-evoked pain attacks in the face.

Trigeminusneuralgi er en alvorlig ansigtssmertelidelse med unilaterale svære stikkende, jagende og/eller skarpe smerter af få sekunders varighed der er lokaliseret i ansigtet.

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	PT
E.1.2	Classification code	10044652
E.1.2	Term	Trigeminal neuralgia
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

1. To evaluate the proportion of subjects classified as responders at the evaluation period (i.e. week 1-4). A subject who meets the following criterion will be classified as a responder: has a reduction of ≥ 30% in mean average daily pain intensity score (mean ADP) assessed using the 11-point numerical rating scale (NRS) during the evaluation period (week 1-4) compared with baseline (weeks -4 to -1). Patients that are protocol violators, e.g., patients having to in-crease current medications or who will undergo surgery in the evaluation period as well as patients who drop out due to worsening of symptoms or side effects will be recorded as non-responders.

E.2.2

Secondary objectives of the trial

To evaluate the proportion of:
- Subjects reaching a reduction of ≥50% and ≥75% respectively in mean ADP during the evaluation period compared with baseline.
- Subjects with a response in mean daily number of paroxysms at evaluation period (i.e. reduction of ≥ 30% in mean of daily number of paroxysms at evaluation period compared with baseline).
- Subjects with a Patient Global Impression of Change (PGIC) scale response at evaluation period ( i.e. has a PGIC response of “much improved” or “very much improved” at week 4.)
To evaluate the change from baseline to week 4 in the active and placebo group respectively:
- Mean ADP.
- Number of paroxysms.
- The Penn Facial Pain Scale-Revised (PENN-FPS-R) score.
To evaluate the percentage of drop-outs in active and placebo group caused by:
- Increased intake of TN-medication.
- Side-effects.
To evaluate the percentage of subjects with side-effects registered in weeks 1-4 during treatment compared with placebo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• A diagnosis of primary TN (idiopathic or classical) according to criteria of The Interna-tional Classification of Headache Disorders 3rd edition.
• Age between 18 and 85 years.
• Subjects must have a minimum mean of 3 TN related pain paroxysms per day with a mean ADP of 4 to 10, inclusive, on the 11-point NRS (0= no pain; 10= maximum pain imaginable) during the 7-day screening phase to enter the baseline phase.
• Subjects must have a minimum mean of 3 TN related pain paroxysms per day with a mean ADP of 4 to 10, inclusive, on the 11-point NRS (0= no pain; 10= maximum pain imaginable) during the 4-week baseline phase to enter the treatment phase (to be ran-domized).

E.4

Principal exclusion criteria

• Significant cardiovascular and cerebrovascular disease such as ischemic heart disease, previous myocardial infarction or previous stroke or transient ischemic attack, major CVD interventions.
• Language difficulties.
• Poor compliance, i.e. unlikely to be able to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject’s and investigator’s knowledge.
• Severe psychiatric disease.
• Anamnestic or clinical symptoms of any kind that are deemed relevant for study partic-ipation by the physician who examines the patient.
• Taking any TN-medication, where the prescribed daily dose has changed within 2 weeks prior to the baseline and evaluation periods (refer to section 6.4 for the list of these medications).
• Pregnant or breastfeeding, or is a female expecting to conceive during the study, includ-ing through 4 weeks after treatment.
• Female subject of childbearing potential who is unwilling to use an acceptable method of effective contraception during the study. Acceptable methods of effective birth control include not having intercourse (true abstinence, when this is in line with the preferred and usual lifestyle of the subject), hormonal birth control methods (pills, shots/injections, implants, or patches), intrauterine devices, surgical contraceptive methods (vasectomy with medical assessment of the surgical success of this procedure or bilateral tubal ligation), or two barrier methods (each partner must use one barrier method) with spermicide - males must use a condom with spermicide; females must choose either a diaphragm with spermicide, OR cervical cap with spermicide, OR contraceptive sponge with spermicide. Female subjects not of childbearing potential are defined as any female who: is post-menopausal by history, defined as:
Age ≥ 55 years with cessation of menses for 12 or more months, OR
Age < 55 years but no spontaneous menses for at least 2 years, OR
Age < 55 years and spontaneous menses within the past 1 year, but currently amenorrhe-ic (eg, spontaneous or secondary to hysterectomy), AND with postmenopausal gonado-tropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of "postmen-opausal range" for the laboratory involved. OR o Underwent bilateral oophorectomy OR o Underwent hysterectomy OR o Underwent bilateral salpingectomy.
• Known sensitivity to any component of erenumab.
• Member of investigational site staff or relative of the investigator.

E.5 End points

E.5.1

Primary end point(s)

1. To evaluate the proportion of subjects classified as responders at the evaluation period (i.e. week 1-4).
a. A subject who meets the following criterion will be classified as a responder:
i. Has a reduction of ≥ 30% in mean average daily pain intensity score (mean ADP) assessed using the 11-point numerical rating scale (NRS) during the evaluation period (week 1-4) compared with baseline (weeks -4 to -1).
ii. Patients that are protocol violators, e.g., patients having to increase cur-rent medications or who will undergo surgery in the evaluation period as well as patients who drop out due to worsening of symptoms or side ef-fects will be recorded as non-responders.
The change/reduction in mean ADP from baseline to evaluation period is calculated as follow-ing: (mean ADP of evaluation period) – (mean ADP of baseline period). If this reduction is ≥ 30% the given subjects is classified as a responder.

E.5.1.1

Timepoint(s) of evaluation of this end point

See above.

E.5.2

Secondary end point(s)

Efficacy:
1. To evaluate the proportion of subjects reaching ≥50% reduction in mean ADP during the evaluation period (week 1-4) compared with baseline (week -4 to -1).

2. To evaluate the proportion of subjects reaching ≥75% reduction in mean ADP during the evaluation period (week 1-4) compared with baseline (week -4 to -1).

3. The proportion of subjects with a response in number of paroxysms at evaluation period.
a. A subject who meets the following criterion will be classified as a responder:
i. Has a reduction of ≥ 30% in mean of daily number of paroxysms during the evaluation period (week 1-4) compared with baseline (week -4 to -1).
The change/reduction in mean number of paroxysms from baseline to evaluation period is cal-culated as following: (mean number of paroxysms of evaluation period) – (mean number of paroxysm of baseline period). If this reduction is ≥ 30% the given subjects is classified as a responder.

4. Proportion of subjects with a Patient Global Impression of Change (PGIC) scale re-sponse at evaluation period. A subject who meets the following criterion will be classi-fied as a responder: has a PGIC response of “much improved” or “very much improved” at week 4.

5. Change from baseline to week 4 in mean ADP in active and placebo group.
This is calculated as following: (mean ADP of evaluation period) – (mean ADP of baseline pe-riod) and is a measure for the absolute change in mean ADP.

6. Change from baseline to week 4 in number of paroxysms in active and placebo group.
This is calculated as following: (mean number of paroxysms of evaluation period) – (mean number of paroxysms of baseline period) and is a measure for the absolute change in mean number of paroxysms.

7. Change from baseline to week 4 in the Penn Facial Pain Scale-Revised (PENN-FPS-R) score.

8. Drop-outs caused by increased intake of TN-medication in active group compared to placebo.

9. Drop-outs caused by side-effect in active group compared to placebo.
Safety:
1. Percentage of subjects with side-effects registered in weeks 1-4 during treatment with erenumab compared with placebo.

E.5.2.1

Timepoint(s) of evaluation of this end point

See above.

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

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

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

GCP Unit Region Hovedstaden

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)

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

2019-04-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-07-29

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-09-13

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