Clinical Trials Register

Summary
EudraCT Number:	2019-001081-15
Sponsor's Protocol Code Number:	APH204
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-04-26
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

2019-001081-15

A.3

Full title of the trial

An exploratory phase II, randomised, double-blind, placebo-controlled, parallel-group study investigating the efficacy and safety of Sepranolone in women with menstrual migraine

A.3.1

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

A study to evaluate the effectiveness and safety of study drug (sepranolone) in women with menstrual migraine

A.4.1

Sponsor's protocol code number

APH204

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	Asarina Pharma ApS
B.1.3.4	Country	Denmark
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	Asarina Pharma ApS
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	Scandinavian CRO AB
B.5.2	Functional name of contact point	Anna Runeson
B.5.3	Address:
B.5.3.1	Street Address	Skolgatan 8
B.5.3.2	Town/ city	Uppsala
B.5.3.3	Post code	75015
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+46703033508
B.5.6	E-mail	anna.runeson@scro.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	Sepranolone
D.3.2	Product code	UC1010
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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	SEPRANOLONE
D.3.9.1	CAS number	516-55-2
D.3.9.2	Current sponsor code	UC1010
D.3.9.4	EV Substance Code	SUB33700
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	25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SEPRANOLONE
D.3.9.1	CAS number	516-55-2
D.3.9.2	Current sponsor code	UC1010
D.3.9.4	EV Substance Code	SUB33700
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	40
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 in pre-filled syringe
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

Menstrual migraine

E.1.1.1

Medical condition in easily understood language

Menstrual migraine

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

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	10065540
E.1.2	Term	Menstrual migraine
E.1.2	System Organ Class	100000004852

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 evaluate the effect of two different doses (10 mg and 16 mg) of sepranolone on number of menstrual migraine days compared with placebo in patients with menstrual migraine.

E.2.2

Secondary objectives of the trial

To investigate the treatment efficacy of Sepranolone as assessed by amount of symptomatic treatment needed
To evaluate the effect of two different doses (10 mg and 16 mg) of sepranolone on number of menstrual migraine days compared with placebo in patients with menstrual migraine.
To investigate the responder rate of Sepranolone on menstrual migraine
To investigate the effect of Sepranolone on auxiliary migraine symptoms
To evaluate the effect of Sepranolone on menstrual migraine related physical and functional impairment in women with menstrual migraine
To evaluate the effect of Sepranolone on the impact of menstrual migraine on everyday activities in patients with menstrual migraine
To evaluate the effect of Sepranolone on the impact of menstrual migraine on overall daily activities in women with menstrual migraine
To measure Sepranolone exposure

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Main Inclusion Criteria
The woman must:
1. provide her informed consent prior to any study related procedures
2. be aged ≥18 and ≤45 years.
3. have a regular menstrual cycle of 24-35 days
4. use sufficient barrier contraception, IUD, be truly abstinent or the woman or her male sexual partner has been surgically sterilized (further described in Section 4.3.1).
5. have a history of migraine according to the IHS classification ICHD-3 with a history of at least 12 months with migraine in conjunction with menstruation and in at least 2 out of 3 ovulatory menstrual cycles.
6. for randomisation, have documented menstrual migraine attacks during at least two menstrual cycles out of the three-cycle screening and baseline period. A menstrual migraine attack is defined as starting at a time between Day -2 and Day +3 of full menstrual flow (limits inclusionary)
Further, the woman may
7. have a total of maximum ten (10) migraine or other headache days per month.

E.4

Principal exclusion criteria

Main Exclusion Criteria
The woman must not have:
1. participated in a clinical study and received active drug in such a study within 30 days or 5 study drug half-lives, whichever the longest, prior to the first study visit.
2. in the investigator's opinion, evidence and/or history of any clinically significant neurological disease, other intracranial or systemic diseases or conditions potentially interfering with study assessments
3. a BMI >35 kg/m2.
4. or has had a malignant disease within the previous 5 years (except non-melanoma skin cancer, cervical or breast ductal carcinoma in situ)
5. HIV or ongoing hepatitis by history
6. have allergies to ingoing study drug components including egg allergy or a history of anaphylactic reactions.
7. have a less than 80% compliance with eDiary reporting during Days -7 until + 7 in each of the three-cycle baseline periods.
The woman must not be:
8. suffering any other medically significant and unstable disease potentially interfering with or being negatively affected by participation in the study, as judged by the investigator.
9. pregnant or breast-feeding, or planning pregnancy during the study period
10. taking any systemic steroid hormonal treatment during 3 months before the study visit. Topical corticosteroids and stable doses of inhalational treatment for asthma or seasonal allergy may be allowed. For injectable hormonal contraceptives, a 6-month washout is required.
11. previously been diagnosed with a major psychiatric disorder according to DSM 5® criteria, including drug abuse or dependency
12. taking disallowed medications or allowed with restrictions with respect to their use prior to or during the study (this list is not comprehensive). Disallowed medications include: corticosteroids, OCTs, over-the-counter or prescription drugs for PMS symptoms, including but not limited to, bioidentical hormones, St John’s wort, Evening primrose oil, Agnus castor.

E.5 End points

E.5.1

Primary end point(s)

Reduction in the menstrual cycle mean number of menstrual migraine Days.
The menstrual cycles need to be ovulatory as demonstrated by mid-luteal phase elevated progesterone levels.

E.5.1.1

Timepoint(s) of evaluation of this end point

During Day -2 to Day +5 of three menstrual cycles, compared to baseline.

E.5.2

Secondary end point(s)

1. Change from baseline in the menstrual cycle number of doses of rescue symptomatic medication taken.
2. Change from baseline of the menstrual cycle mean number of migraine Days. The menstrual cycles need to be ovulatory as demonstrated by mid-luteal phase elevated progesterone levels.
3. Change from baseline of the menstrual cycle mean number of days with moderate or severe migraine.
4. Change from baseline of number of days with moderate or severe migraine.
5. Proportion of women having 30%-50%-75%-100% or more reduction in number of migraine Days.
6. Change from baseline in the menstrual cycle auxiliary migraine symptoms in patients’ reporting of associated symptoms (nausea, vomiting, photophobia, phonophobia)
7. Change from baseline in the menstrual cycle on the Migraine Physical Function Impact Diary score 24-hour recall version during Day –2 – Day +5.
8. Change from baseline in the menstrual cycle on the composite functional endpoint/ MM scale Change from baseline in Migraine Physical Function Impact Diary score 24-hour recall version.
9. Change from baseline in the menstrual cycle on the global impact on daily activities endpoint/ MM scale Change from baseline in Migraine Physical Function Impact Diary score 24-hour recall version.
10. Plasma levels of isoallopregnanolone.
11.Reduction in the menstrual cycle mean number of migraine days per menstrual cycle . The menstrual cycles need to be ovulatory as demonstrated by mid-luteal phase elevated progesterone levels.
12. Reduction in the menstrual cycle mean number of migraine days per month, compared to baseline. The menstrual cycles need to be ovulatory as demonstrated by mid-luteal phase elevated progesterone levels.
13. Reduction in the menstrual cycle mean number of migraine Days during the full treatment period, compared to baseline . The menstrual cycles need to be ovulatory as demonstrated by mid-luteal phase elevated progesterone levels.
14. Change from baseline in the menstrual cycle number of doses of rescue symptomatic medication taken per menstrual cycle .

E.5.2.1

Timepoint(s) of evaluation of this end point

1, 9 During Day -2 to Day +5 during three consecutive menstrual cycles.
2. Between Day -2 to Day +5 during the last two out of three consecutive menstrual cycles.
3. Between Day -2 to Day +5 during three consecutive menstrual cycles.
4. Between Day -2 to Day +5 during the last two out of three consecutive menstrual cycles.
5. During Days -2 to Day +5 vs. baseline.
8. 6, 7, 9, 14 During three consecutive menstrual cycles
6, 7, 9 During the last two out of three consecutive menstrual cycles.
8. During Day –2 – Day +5 during the last two out of three consecutive menstrual cycles.
10. Blood sampling done on Day -7 ±2 during screening and each treatment cycle.
11. During three menstrual cycles, compared to baseline
12. Mean number of migraine days per month, compared to baseline

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

Yes

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

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

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

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 undergoing 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)

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

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.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

2019-06-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-06-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-04-06

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