Clinical Trials Register

Summary
EudraCT Number:	2021-005496-39
Sponsor's Protocol Code Number:	APHP211042
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-10-20
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

France - ANSM

A.2

EudraCT number

2021-005496-39

A.3

Full title of the trial

Prospective, randomized, double-blind, placebo controlled, multicenter study assessing the efficacy of intracavernosal Clostridium Botulinum neurotoxin type A (Xeomin®) 100U as add-on therapy to sildenafil 100 mg on demand compared to sildenafil 100 mg on demand for the treatment of erectile dysfunction (ED) not sufficiently responsive to standard therapy with phosphodiesterase type 5 inhibitors

Étude multicentrique prospective, randomisée, en double aveugle, contrôlée par placebo, évaluant l'efficacité de la neurotoxine intracaverneuse de Clostridium Botulinum de type A (Xeomin®) 100U en traitement d'appoint au sildénafil 100 mg à la demande par rapport au sildénafil 100 mg à la demande pour le traitement de dysfonction érectile (DE) pas suffisamment sensible au traitement standard avec des inhibiteurs de la phosphodiestérase de type 5

A.3.1

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

Étude multicentrique prospective, randomisée, en double aveugle, contrôlée par placebo, évaluant l'efficacité de la neurotoxine intracaverneuse de Clostridium Botulinum de type A(Xeomin®) 100U en traitement d'appoint au sildénafil 100 mg à la demande par rapport au sildénafil 100 mg à la demande pour le traitement de dysfonction érectile (DE) pas suffisamment sensible au traitement standard avec des inhibiteurs de la phosphodiestérase de type 5

A.3.2

Name or abbreviated title of the trial where available

MENOX

A.4.1

Sponsor's protocol code number

APHP211042

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information

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	XEOMIN
D.2.1.1.2	Name of the Marketing Authorisation holder	MERZ PHARMACEUTICALS GMBH
D.2.1.2	Country which granted the Marketing Authorisation	France
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	XEOMIN
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intracavernous use
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	Yes
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	Powder for solution for injection
D.8.4	Route of administration of the placebo	Intracavernous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Erectile dysfunction

Dysfonction érectile

E.1.1.1

Medical condition in easily understood language

to facilitate long-lasting cavernosal smooth muscle relaxation through an alteration of the balance within the erectile

pour faciliter la relaxation durable des muscles lisses caverneux grâce à une altération de l'équilibre au sein du tissu érectile

E.1.1.2

Therapeutic area

Diseases [C] - Male diseases of the urinary and reproductive systems [C12]

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	10020381
E.1.2	Term	Hormonal imbalance
E.1.2	System Organ Class	100000004848

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 investigate the efficacy of intracavernosal Clostridium Botulinum neurotoxin type A(Xeomin®) 100U as add-on therapy to sildenafil 100 mg on demand in men with ED and insufficient response to standard oral therapy with sildenafil 100 mg on demand during the 4-week open-label run-in-phase.

E.2.2

Secondary objectives of the trial

The secondary objectives are to further describe the efficacy and safety of Clostridium Botulinum neurotoxin type A(Xeomin®) 100U IC as add-on therapy to sildenafil 100 mg on demand.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- For the open-label run-in phase (4 week duration):

Subjects have to fulfill all of the following criteria before being included in the open-label run-in phase:
1. Written informed consent signed before any study-specific procedure
2. History of ED for at least 6 months prior to screening, defined as “the inability to achieve and maintain an erection of the penis sufficient to complete satisfactory sexual intercourse”. The diagnosis of ED had to be confirmed by a physician
3. Stable, heterosexual relationship for at least 6 months prior to screening
4. Aged ≥18 to ≤ 80 years at visit 1 the first screening examination
5. Highly motivated to obtain treatment for ED according to physician judgment
6. History of previous use of at least 1 marketed PDE5-I and insufficient
therapeutic efficacy despite use of the highest approved dose
7. Ability to understand and follow study-related instructions

- For the double-blind treatment phase (3 month duration):

Subjects have to fulfill all of the following criteria before being included in the double-blind treatment phase:
1. At least 4 attempts at sexual intercourse on 4 separate days during the open-label run-in phase with use of 100 mg sildenafil approximately 1 hour before attempting intercourse (according to the answer to the following question in the Subject Diary: “Was sexual activity initiated with the intention of intercourse?”)
2. IIEF-EF score <17
3. At least 50% of attempts at sexual intercourse during the open-label run-in phase had been unsuccessful, i.e. the following question in the Subject Diary had to be answered with “No”: “Did your erection last long enough for you to have successful intercourse?”
(SEP 3: success in maintenance of erection)
4. Highly motivated to obtain treatment for ED
5. Ability to understand and follow study-related instructions

E.4

Principal exclusion criteria

1. Hypersensitivity to the active substance (Clostridium Botulinum neurotoxin type A) or to any of the excipients (Human albumin, sucrose)

Any cardiovascular condition, incl. unstable angina pectoris that would have precluded sexual activity
2. History of myocardial infarction, stroke within 6 months prior to screening
3. Presence of penile anatomical abnormalities such as penile fibrosis or Lapeyronie’s disease which, in the investigator’s opinion, would have significantly impaired sexual performance4. Concomitant use of nitrates / nitric oxide donors
4. Generalized disorders of muscle activity (e.g. myasthenia gravis, Lambert-Eaton syndrome)
5. Prior injection of botulinum toxin A in any site for any indication

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the change in the erectile function between baseline and month 3, measured by the International Index of Erectile Function – Erectile Function subscale (IIEF-EF). The International Index of Erectile Function (IIEF) is a 15-item self-report instrument assessing male sexual function. The Erectile Function (EF) domain score of the IIEF, comprised of items 1 to 5 and 15 from the IIEF, is used in this study.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 month; 3 month; 6month and 9 month

E.5.2

Secondary end point(s)

i. The Sexual Encounter Profile (SEP). The SEP is a log diary with 5 questions answered after each sexual intercourse attempt, providing information as to whether the erection was hard enough to penetrate (SEP 2), or whether it was maintained for completion (SEP 3) or a satisfactory sexual experience (SEP 4).

ii. The Erection Hardness Score (EHS). The EHS is a single-item Likert scale. The tool asks men to consider the question ‘How would you rate the hardness of your erection?’ and select one of the options below:
0 – Penis does not enlarge
1 – Penis is larger, but not hard
2 – Penis is hard, but not hard enough for penetration
3 – Penis is hard enough for penetration, but not completely hard
4 – Penis is completely hard and fully rigid

iii. Global Assessment Question (GAQ1): “Has the treatment you have been taking over the past 4 weeks improved your erections? (Please compare your current erections after treatment with your erections before your participation in this study)”: yes or no and if necessary GAQ2 ‘If yes, has the treatment improved your ability to engage in sexual activity?’
iv. Persistence of efficacy at 6 and 9 month post- Xeomin® 100U IC using the same tools: IIEF-EF, SEP, EHS, GAQ

For safety: Nature, number and severity of adverse events

E.5.2.1

Timepoint(s) of evaluation of this end point

1 month; 3 month; 6month and 9 month

M1; M3; M6; et M9

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

Last visit at 10 month

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:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

126

F.2 Gender

F.2.1

Female

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

226

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)

Patients will continue to be followed by the urologist for the rest of their treatment at the end of the research

Les patients continueront à se faire suivre par l'urologue pour la suite de leur prise en charge à la fin de la recherche

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

2021-12-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-12-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-07-23

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