Clinical Trials Register

Summary
EudraCT Number:	2021-005719-29
Sponsor's Protocol Code Number:	D-FR-52014-245
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:	2022-04-12
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2021-005719-29

A.3

Full title of the trial

An open-label, multicentre, single arm study to assess the efficacy and safety of triptorelin 6-month formulation administered subcutaneously in participants with locally advanced and/or metastatic prostate cancer previously treated and castrated with a GnRH analogue

Étude multicentrique en ouvert, à un seul bras, évaluant l’efficacité et la sécurité de la formulation de triptoréline-6 mois administrée par voie sous-cutanée chez des participants atteints d’un cancer de la prostate localement avancé et/ou métastatique précédemment traité et castré avec un analogue de la GnRH.

A.3.1

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

Effects of triptorelin when given every 6-months under the skin to adult males
with cancer in the prostate

Effets de la triptoréline administrée tous les 6 mois sous la peau chez des patients adultes ayant un cancer de la prostate

A.4.1

Sponsor's protocol code number

D-FR-52014-245

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	Ipsen Pharma SAS
B.1.3.4	Country	France
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	Ipsen Pharma SAS
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ipsen Bioinnovation
B.5.2	Functional name of contact point	Medical Monitor
B.5.3	Address:
B.5.3.1	Street Address	102 Park Drive
B.5.3.2	Town/ city	Milton Park, Oxfordshire
B.5.3.3	Post code	OX14 4RY
B.5.3.4	Country	United Kingdom
B.5.6	E-mail	muhammad.shoaib.ext@ipsen.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	Decapeptyl
D.2.1.1.2	Name of the Marketing Authorisation holder	Ipsen Pharmaceuticals 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.3.4	Pharmaceutical form	Powder and solvent for suspension 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	TRIPTORELIN
D.3.9.1	CAS number	57773-63-4
D.3.9.3	Other descriptive name	Triptorelin embonate (pamoate)
D.3.9.4	EV Substance Code	SUB11324MIG
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	22.5
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	Yes
D.3.11.13.1	Other medicinal product type	Triptorelin is an agonist analogue of natural GnRH.

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

prostate cancer

cancer de la prostate

E.1.1.1

Medical condition in easily understood language

prostate cancer

cancer de la prostate

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	24.1
E.1.2	Level	LLT
E.1.2	Classification code	10085679
E.1.2	Term	Locally advanced prostate cancer
E.1.2	System Organ Class	100000004864

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 efficacy of triptorelin embonate 22.5 mg 6-month formulation administered subcutaneously in maintaining serum testosterone castrate levels in
participants with advanced prostate cancer previously treated and castrated with a
GnRH analogue.

Évaluer l’efficacité de la formulation de triptoréline embonate-6 mois (22,5 mg) administrée par voie sous-cutanée dans le maintien de taux de testostéronémie de castration chez des participants atteints d’un cancer de la prostate avancé précédemment traité et castré avec un analogue de la GnRH.

E.2.2

Secondary objectives of the trial

- To evaluate the efficacy of triptorelin embonate 22.5 mg 6-month formulation
administered subcutaneously on castration;
- To evaluate the efficacy of triptorelin embonate 22.5 mg 6-month formulation
administered subcutaneously on testosterone levels <0.694 nmol/L (20 ng/dL);
- To demonstrate the effect of triptorelin embonate 22.5 mg 6-month formulation administered subcutaneously to suppress the ‘acute-on-chronic’ effect following the administration of the second dose;
- To demonstrate the effect of triptorelin embonate 22.5 mg 6-month formulation administered subcutaneously in the maintenance of PSA;
- To demonstrate the safety profile of triptorelin embonate 22.5 mg 6-month
formulation administered subcutaneously;

- Evaluer l’efficacité de la formulation de triptoréline embonate-6 mois (22,5 mg) administrée par voie sous-cutanée sur la castration
- Evaluer l’efficacité de la formulation de triptoréline embonate-6 mois (22,5 mg) administrée par voie sous-cutanée sur le maintien de taux de testostéronémie < 0,694 nmol/l (20 ng/dl)
- Démontrer l’effet de la formulation de triptoréline embonate-6 mois (22,5 mg) administrée par voie sous-cutanée sur la suppression du phénomène « aigu-sur-chronique » (ou micro-poussée) après l’administration de la deuxième dose
- Démontrer l’effet de la formulation de triptoréline embonate-6 mois (22,5 mg) administrée par voie sous-cutanée sur le maintien du taux d’antigène prostatique spécifique (PSA, prostate-specific antigen)
- Démontrer le profil de sécurité de la formulation de triptoréline embonate-6 mois (22,5 mg) administrée par voie sous-cutanée

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Participant is male and must be 18 years of age inclusive, at the time of signing the informed consent.
2. Participant has histologically or cytologically proven prostate cancer with rising PSA after failed local therapy or metastatic disease, or requiring radiotherapy, and be a candidate for long-term (i.e. >1 year) androgen deprivation therapy.
3. Participant requires a GnRH analogue treatment for a minimum of 18 months, of which a minimum of 3 months of GnRH analogue treatment has already been provided prior to screening. (Note: participants must receive study intervention on Day 1 in accordance with the treatment schedule of their previously received GnRH analogue therapy).
4. Has serum testosterone levels <1.735 nmol/L (50 ng/dL) at screening.
5. Has Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 (see Appendix 10.4).
6. Has a life expectancy of >18 months.
7. Male participants must agree that, if their partner is at risk of becoming pregnant (although highly unlikely in this study population), they will use an effective method of contraception. The participant must agree to use the contraception during the whole of the study and for 9 months after the last dose of study intervention.
8. Capable of giving signed informed consent as described in Appendix 10.1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

1. Participant de sexe masculin âgé d’au moins 18 ans au moment de la signature du formulaire de consentement éclairé.
2. Présence d’un cancer de la prostate histologiquement et cytologiquement prouvé, avec augmentation des taux de PSA après un échec de traitement local ou une atteinte métastatique, ou nécessitant une radiothérapie et participant candidat pour un traitement par privation androgénique à long terme (c’est-à-dire > 1 an).
3. Nécessité d’un traitement par analogue de GnRH pendant un minimum de 18 mois, dont un minimum de 3 mois de traitement par analogue de GnRH déjà administré avant la sélection. (Remarque : les participants devront recevoir le traitement à l’étude le Jour 1 conformément au calendrier de traitement de leur traitement précédent par analogue de GnRH.)
4. Testostéronémie < 1,735 nmol/l (50 ng/dl) à la sélection.
5. Score de performances ECOG (Eastern Cooperative Oncology Group) de 0 à 1 (se reporter à l’Annexe 10.4 du protocole).
6. Espérance de vie > 18 mois
7. Un participant dont la partenaire présente un risque de grossesse (bien que hautement improbable dans cette population à l’étude) devra accepter d’utiliser un moyen de contraception efficace. Le participant devra utiliser ce moyen de contraception pendant l’intégralité de l’étude et les 9 mois suivant la dernière dose du traitement à l’étude.
8. Capacité à fournir un consentement éclairé signé conformément à ce qui est décrit dans l’Annexe 10.1 du protocole, ce qui inclut le respect des exigences et restrictions répertoriées dans le formulaire de consentement éclairé (FCE) et dans ce protocole

E.4

Principal exclusion criteria

Medical conditions
1.Presence of another neoplastic lesion or brain metastases.
2.Metastatic hormone-sensitive prostate cancer with high tumour burden
3.Metastatic castration-resistant prostate cancer
4.Any concomitant disorder or resulting therapy that is likely to interfere with participant compliance or with the study in the opinion of the investigator.

Prior/concomitant therapy
5.Use of finasteride (Proscar®) or dutasteride (Avodart®/Avolve®) within the past 6 months
6.Planned intermittent scheme of GnRH analogue
7.Use of any other therapy for prostate cancer during the study (e.g. chemotherapy)
8.Prior hypophysectomy or adrenalectomy

Prior/concurrent clinical study experience
9.Participation in another study with an experimental drug within 3 months before signing informed consent or within five half-lives of the investigational drug (whichever was the longer), or any other type of medical research.
Diagnostic assessments
10.Severe kidney or liver failure (creatinine >2 times the normal range, aspartate aminotransferase and alanine aminotransferase >3 times the normal range)

Other exclusions
11.Any concomitant disorder or resulting therapy that is likely to interfere with participant’s compliance, the subcutaneous administration of the drug or with the study in the opinion of the investigator.
12.Previous history of QT prolongation or concomitant use of medicinal products known to prolong the QT interval or with a known risk of torsades de pointes
13.Known hypersensitivity to triptorelin or any of its excipients, GnRH, other GnRH agonist/analogues.
14.Known active use of recreational drug or alcohol dependence in the opinion of the investigator
15.Inability to give informed consent or to comply fully with the protocol.

Pathologies médicales
1. Présence d’une autre lésion néoplasique ou de métastases cérébrales.
2. Cancer de la prostate hormonosensible métastatique à haute charge tumorale
3. Cancer de la prostate métastatique résistant à la castration
4. Toute pathologie concomitante ou le traitement résultant, susceptible d’interférer avec l’observance du participant ou avec l’étude, d’après l’investigateur.

Médicaments antérieurs/concomitants
5. Utilisation de finastéride (Proscar®) ou de dutastéride (Avodart®/Avolve®) au cours des 6 mois précédent
6. Schéma intermittent prévu de traitement par analogie de la GnRH
7. Utilisation de tout autre traitement contre le cancer de la prostate pendant l’étude (par exemple chimiothérapie)
8. Antécédents d’hypophysectomie ou de surrénalectomie

Expérience d’étude clinique antérieure/concomitante
9. Participation à une autre étude évaluant un médicament expérimental au cours des 3 mois précédant la signature du consentement éclairé ou dans les cinq demi-vies du médicament expérimental (selon la durée la plus longue) ou à tout autre type de recherche médicale.
Évaluations diagnostiques
10. Insuffisance rénale ou hépatique sévère (créatinine > 2 fois la plage de valeurs normales, aspartate aminotransférase et alanine aminotransférase > 3 fois la plage de valeurs normales)

Autres critères de non-inclusion
11. Toute pathologie concomitante ou le traitement résultant, susceptible d’interférer avec l’observance du participant, l’administration sous-cutanée du médicament ou avec l’étude, d’après l’investigateur.
12. Antécédents d’allongement de l’intervalle QT ou utilisation concomitante d’un médicament connu pour allonger l’intervalle QT ou présentant un risque connu de torsades de pointes.
13. Hypersensibilité connue à la triptoréline ou à l’un de ses excipients, à la GnRH, ou autres agonistes/analogues de GnRH.
14. Utilisation active connue de substances à usage récréatif ou dépendance connue à l’alcool, selon l’avis de l’investigateur
15. Incapacité à fournir son consentement éclairé ou à respecter totalement le protocole.

E.5 End points

E.5.1

Primary end point(s)

Percentage of participants maintaining castrate levels of serum testosterone during
the study (maintenance of castration defined as testosterone <1.735 nmol/L (50 ng/dL) at Day 29, Day 85, Day 141, Day 169, Day 253, Day 309 and Day 337)

Pourcentage de participants maintenant des taux de testostéronémie de castration pendant l’étude (maintien de taux de castration définis comme une testostéronémie < 1,735 nmol/l (50 ng/dl) au Jour 29, Jour 85, Jour 141, Jour 169, Jour 253, Jour 309 et Jour 337)

E.5.1.1

Timepoint(s) of evaluation of this end point

Please refer to E.5.1

Cf. E.5.1

E.5.2

Secondary end point(s)

- Percentage of participants castrated at each
timepoint on Day 29, Day 85, Day 141, Day 169, Day 253, Day 309 and Day 337
(castration defined as testosterone <1.735 nmol/L (50 ng/dL)).
- Percentage of participants with a serum testosterone level <0.694 nmol/L (20 ng/dL) during the study.
- Percentage of participants with a serum testosterone level <0.69 nmol/L (20 ng/dL) at each timepoint on Day 29, Day 85, Day 141, Day 169, Day 253, Day 309 and Day 337.
- Percentage of participants castrated on Day 3 and Day 7 after each injection administered on Day 1 and Day 169 (castration defined as testosterone
<1.735 nmol/L (50 ng/dL)).
- Percent change in PSA from baseline (prior to injection) at Day 169 and Day 337 (Percent change in PSA defined as the absolute value of difference between the PSA values at Day 169 and Day 337 and the baseline value divided by the baseline value).
- Incidence of TEAEs (including local tolerability) throughout the study i.e. up to
Day 337.
- Change from baseline in clinical safety laboratory parameters (blood chemistry and haematology) at Day 337
- Change from baseline in physical examination at Day 169 and Day 337
- Change from baseline in ECG at Day 337
- Change from baseline in vital signs (blood pressure and heart rate) at each visit up to Day 337

- Pourcentage de participants castrés à chaque point temporel au Jour 29, Jour 85, Jour 141, Jour 169, Jour 253, Jour 309 et Jour 337 (taux de castration définis comme une testostéronémie < 1,735 nmol/l (50 ng/dl))
- Pourcentage de participants ayant un taux de testostéronémie < 0,694 nmol/l (20 ng/dl) pendant l’étude
- Pourcentage de participants ayant un taux de testostéronémie < 0,694 nmol/l (20 ng/dl) à chaque point temporel au Jour 29, Jour 85, Jour 141, Jour 169, Jour 253, Jour 309 et Jour 337
- Pourcentage de participants castrés, au Jour 3 et au Jour 7 après chaque injection administrée au Jour 1 et au Jour 169 (taux de castration définis comme une testostéronémie < 1,735 nmol/l (50 ng/dl))
- Pourcentage de variation du taux de PSA par rapport aux valeurs initiales (avant l’injection) au Jour 169 et au Jour 337
(Pourcentage de variation du taux de PSA défini comme la valeur absolue de la différence entre les taux de PSA mesurés au Jour 169 et au Jour 337 et à l’inclusion, divisée par la valeur initiale mesurée à l’inclusion)
- Incidence des EIAT (y compris tolérance locale) pendant toute l’étude, c’est-à-dire jusqu’au Jour 337
- Variation des paramètres biologiques cliniques de sécurité (biochimie sanguine et hématologie) au Jour 337 par rapport aux valeurs initiales
- Variation de l’examen clinique au Jour 169 et au Jour 337 par rapport aux valeurs initiales
- Variation de l’examen ECG au Jour 337 par rapport aux valeurs initiales
- Variation des signes vitaux (pression artérielle et fréquence cardiaque) à chaque visite jusqu’au Jour 337, par rapport aux valeurs initiales

E.5.2.1

Timepoint(s) of evaluation of this end point

Please refer to E.5.2

Cf. E.5.2

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)

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

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

LPLV

Dernière visite du dernier patient

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

122

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

153

F.4.2.2

In the whole clinical trial

153

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

2022-08-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-05-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-07-08

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials