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    Summary
    EudraCT Number:2021-005344-30
    Sponsor's Protocol Code Number:TETRA-pilot
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2022-05-27
    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.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2021-005344-30
    A.3Full title of the trial
    TETRA-pilot: Testosterone in transgender women after vaginoplasty: a dose-finding and feasibility pilot study
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Dose and feasibility of testosterone in transgender women
    A.3.2Name or abbreviated title of the trial where available
    TETRA-pilot
    A.4.1Sponsor's protocol code numberTETRA-pilot
    A.5.4Other Identifiers
    Name:File number toetsingonlineNumber:NL79312.029.21
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAmsterdam UMC, location VUmc
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAmsterdam UMC, location VUmc
    B.4.2CountryNetherlands
    B.4.1Name of organisation providing supportKyowa Kirin Services Limited
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmsterdam UMC, location VUmc
    B.5.2Functional name of contact pointProject contact
    B.5.3 Address:
    B.5.3.1Street AddressDe Boelelaan 1117
    B.5.3.2Town/ cityAmsterdam
    B.5.3.3Post code1081HV
    B.5.3.4CountryNetherlands
    B.5.4Telephone number31204444307
    B.5.5Fax number31204444312
    B.5.6E-mailn.c.gieles@amsterdamumc.nl
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Tostran 2% Gel
    D.2.1.1.2Name of the Marketing Authorisation holderKyowa Kirin
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTostran 2% Gel
    D.3.2Product code RVG 33424
    D.3.4Pharmaceutical form Gel
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPTransdermal use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Low testosterone levels in transgender women who underwent a vaginoplasty. We will investigate the serum testosterone levels at different doses of testosteron gel and if there are side effects.
    E.1.1.1Medical condition in easily understood language
    Transgender women who underwent a genital operation may have very low testerone levels. We will study the effect of different dosages of testosterone gel and if there are side effects.
    E.1.1.2Therapeutic area Body processes [G] - Physiological processes [G07]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To establish dose-response relationships to achieve testosterone levels between 1.5-2.5 nmol/l with daily use of 2% transdermal testosterone (Tostran®) at different dosages in transgender women after vaginoplasty.
    To study side effects of androgenism at the different dosages (facial hair growth, acne, depilation rate, alopecia)
    E.2.2Secondary objectives of the trial
    To assess the applicability and patient evaluation a clinical outcome symptoms questionnaire on hypogonadal symptoms (energy, sleep, cognition, vitality, mood, quality of life, sexual function and arousability).
    To assess safety (blood pressure, heartrate, BMI, laboratory measurements)
    If additional consent is provided, to explore feasibility of measurement and potential effects on vaginal pulse amplitude during arousal.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Start of gender affirming hormone therapy at or after 18 years of age
    - Current use of estradiol therapy with good compliance for at least six months
    - Underwent vaginoplasty at least 6 months ago
    - Sufficient knowledge of the Dutch language
    - BMI 18-35 kg/m2
    - Testosterone levels <0.8 nmol/l measured since vaginoplasty
    - To participant in optional vaginal pulse amplitude measurement: minimal self-reported vaginal depth of five centimeters
    E.4Principal exclusion criteria
    - No regular follow-up visits at the clinic for gender dysphoria in the past four years
    - Current use of testosterone therapy
    - Current untreated clinical depression
    - Severe familial dyslipidemia (e.g. Familial Hypercholesterolemia)
    - Serum estradiol concentration lower than 150 pmol/l or higher than 700 pmol/L the VUmc reference range (150-700 pmol/L) at last visit prior to baseline.
    - Mental health issues that prevent participation
    - Current use of anticoagulation treatment or corticosteroids
    - Any of the following contraindications for the use of testosterone gel (Tostran®): Known, past or suspected breast cancer; Known or suspected estrogen-dependent malignant tumours (e.g genital tract carcinoma); Acute liver disease, or a history of liver disease as long as liver function tests have failed to return to normal (<2.5xULN); Porphyria; Cerebral hemorrhage; Known hypersensitivity to the active substances or to any of the excipients (Propylene glycol, Ethanol anhydrous, Isopropyl alcohol, Oleic acid, Carbomer 1382, Trolamine, Butylhydroxytoluene (E321), Hydrochloric acid (used for pH adjustment)); Interfering medication (SPC).
    E.5 End points
    E.5.1Primary end point(s)
    The first main end point of this study is the total testosterone level during the different dosages in the dose-escalation phase and after two months of dose continuation at the established dose. Serum testosterone concentrations will be determined using liquid-chromatography tandem mass spectrometry (LC-MS/MS) which is an accurate determination methods for testosterone concentrations in the low ranges.

    The second main endpoint of the study are changes in symptoms of androgenism. For these, we use the Hirsuta pictoral questionnaire to assess hair growth and self-developed questions on acne, depilation rate, alopecia and application site symptoms.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At baseline, after two weeks and optionally at six and ten weeks. Subsequently, after one and two months.



    E.5.2Secondary end point(s)
    Secondary outcomes measures include the applicability and feasibility of a clinical symptoms questionnaire designed to assess hypogonadal symptoms. This includes the following questionnaires: the HIS-Q questionnaire excluding the questions on sexuality, the Changes in Sexual Function Questionnaire-14 Female, the Sexual Excitation Scale the Cantril ladder, the vitality subscale of the Short-Form 36, the PROMIS Depression short form , the PROMIS anxiety short form and Sexual Desire Inventory and two sets of self-developed questions on demographic background and sexual satisfaction. After filling in the questionnaire, participants will be asked self-constructed questions on the clarity, suitability and completeness of the questionnaire for the assessment of symptoms from low testosterone.

    Additional laboratory measurements include 17-beta-estradiol, LH, FSH, prolactin, SHBG, LDL and HDL cholesterol and triglycerides.

    The following patient characteristics will be recorded: age, height, weight, BMI, blood pressure, heart rate, alcohol use, smoking, family history and type and dose of estradiol use.

    If additional consent is provided, feasibility of measurement and potential effect of testosterone therapy on vaginal pulse amplitude during arousal within participants.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Participants are asked to fill in and assess the clinical symptoms questionnaire during the first and last visit of the study.

    At baseline and at each subsequent visit patient characteristics will be recorded.

    Participants will have blood drawn at baseline and at two weeks, and if dose-escalation occurs at six weeks and ten weeks after baseline, and at every month during the two-month dose-continuation phase.

    If additional consent is provided, vaginal pulse amplitude will be measured in the week after signing the informed consent and in the week before the final visit.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy No
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial 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.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 10
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    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 in principle, regular care with the endocrinologist will be continued. If participants wish to continue using low dose testosterone therapy off label, they will be allowed to do so provided that no severe side effects take place during the trial that require the person to cease therapy for safety reasons. This will be prescribed and monitored by the endocrinologist as part of regular care visits.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-06-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-05-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2023-08-23
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