Klinefelter syndrome – the effect of Testosterone treatment In PubertY A randomized, double-blind placebo-controlled intervention study ‘The TiPY study’

2023-505854-16-00 Therapeutic use (Phase IV) Ongoing, recruiting

Start 1 Apr 2025 · Status Ongoing, recruiting · 1 EU/EEA countries · 4 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ongoing, recruiting
Participants planned 32
Countries 1
Sites 4

47,XXY (Klinefelter syndrome)

The primary study objective is to evaluate the effect of two years testosterone replacement therapy (TRT) during puberty in boys with Klinefelter syndrome on • changes in body composition

Key facts

Sponsor
Rigshospitalet
Participant type
Pediatric, Patients
Age range
0-17 years
Gender
Male
Therapeutic area
Diseases [C] - Hormonal diseases [C19], Diseases [C] - Male Urogenital Diseases [C12]
Trial duration
1 Apr 2025 → ongoing
Decision date (initial)
2023-09-20
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
The Novo Nordisk Foundation · Rigshospitalet’s Research council (part time research employment for three years for Lise Aksglæde)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary study objective is to evaluate the effect of two years testosterone replacement therapy (TRT) during puberty in boys with Klinefelter syndrome on
• changes in body composition

Secondary objectives 8

  1. The secondary study objectives are to evaluate effects of two years testosterone replacement therapy (TRT) during puberty in boys with Klinefelter syndrome on • pubertal development and virilization
  2. Effect on growth and body proportions
  3. Effect on lipid and glucose metabolism and systemic inflammation
  4. Effect on neurocognitive development, adaptive behavioral functioning, psychopathology and quality of life
  5. Effect on bone mineralization
  6. Effect on muscle strength
  7. Effect on QTc (ECG)
  8. Effect on fertility

Conditions and MedDRA coding

47,XXY (Klinefelter syndrome)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1. *Boys with Klinefelter syndrome (with a 47,XXY karyotype verified by conventional chromosome analysis or ArrayCGH). *Age 10-14 years at inclusion *LH > +2 standard deviations (SD) by ultrasensitive LH assay *Free T<+2SD *Signed consent from parents

Exclusion criteria 1

  1. *Previous or ongoing T treatment except for TRT because of micropenis during minipuberty *Contraindications to testosterone treatment *Participation in any other clinical trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Change in body composition as evaluated by whole body dual energy x-ray absorptiometry (DEXA) scan and measurement of body fat percentage, ratio between android and gynoid fat percentage and muscle mass.

Secondary endpoints 8

  1. Pubertal development (Tanner stageing), voice frequency and measurement of reproductive hormones in serum.
  2. Height, weight, sitting-height, head circumference, arm span, measurement of IGF1, IGF1BP3 in serum, and evaluation of bone age (xray)
  3. serum cholesterol (total, HDL, LDL), triglyceride, free fatty acids, glycerol, adiponectin, leptin, glucose, insulin, HbA1C, IL-6, TNF-α, IL-1RA, hsCRP/CRP
  4. neuropsychological assessment before and after 2 year treatment
  5. Bone health evaluated by whole body DEXA and Bone Health Index (BHI), and measurement of bone turnover markers (25-OH-vitamin D, calcium, phosphate, magnesium, PTH, alkaline phosphatase (liver and bone), osteocalcin, PINP (procollagen type I N-terminal propetide), CTX (carboxy terminal telopeptide of collagen type I), RANKL (receptor activator of nuclear factor kappa-B ligand), OPG (osteoprogeterin), Klotho, sclerostin and TRACP 5b (tartrate-resistant acid phosphatase 5b)
  6. grip-strength
  7. Electrocardiogram with evaluation of QTc
  8. Semen quality (if the boy is able and willing to deliver a semen sample)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

AndroGel 1%

PRD10703493 · Product

Active substance
Testosterone
Pharmaceutical form
GEL
Route of administration
TRANSDERMAL USE
Max daily dose
50 mg milligram(s)
Max total dose
36500 mg milligram(s)
Max treatment duration
24 Month(s)
Authorisation status
Not Authorised
MA holder
REGION HOVEDSTADENS APOTEK
Paediatric formulation
No
Orphan designation
No

Placebo 1

The placebo consists of a gel for transdermal application. It is manufacured by Besins Healthcare in France. It is provided in bottles with a pump. The bottles are identical to the bottles with Androgel 1%.

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

94 Total trials 54 Recruiting 24 Ended
Academic / Non-commercial
Sponsor organisation
Rigshospitalet
Address
Blegdamsvej 9
City
Copenhagen Oe
Postcode
2100
Country
Denmark

Scientific contact point

Organisation
Rigshospitalet
Contact name
Lise Aksglaede

Public contact point

Organisation
Rigshospitalet
Contact name
Lise Aksglaede

Third parties 1

OrganisationCity, countryDuties
Frederiksberg Hospital
ORG-100028217
 Frederiksberg, Denmark On site monitoring

Locations

1 EU/EEA country · 4 investigational sites

By country

CountryMS statusPlanned subjectsSites
Denmark Ongoing, recruiting 32 4
Rest of world — 0 —

Investigational sites

Denmark

4 sites · Ongoing, recruiting
Aalborg University Hospital
Department of Pediatrics, Ladegaardsgade 5, 9000, Aalborg
Rigshospitalet
Department of Growth and Reproduction, Blegdamsvej 9, 2100, Copenhagen Oe
Aarhus Universitetshospital
Department of Paediatrics and Adolescent Medicine, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N
Odense University Hospital
Hans Christian Andersen Children’s Hospital, Kloevervaenget 47, 5000, Odense C

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Denmark 2025-04-01 2025-04-01

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) CTIS protocol 6
Protocol (for publication) Evaluation plan 3
Protocol (for publication) Pain questionnaire 1
Protocol (for publication) Randomization at Region Hovedstadens Apotek 1
Protocol (for publication) Stamdata 2
Recruitment arrangements (for publication) Recruitment 2
Subject information and informed consent form (for publication) Deltagerinfomation til deltagere mellem 15 og 17 ar 1
Subject information and informed consent form (for publication) Deltagerinformation til deltagere der fylder 18 ar under follow up 1
Subject information and informed consent form (for publication) Deltagerinformation til deltagere_10-14 ar 3
Subject information and informed consent form (for publication) Deltagerinformation til forldre 2
Subject information and informed consent form (for publication) Dine rettigheder som forsgsperson i forsg med medicin 2
Subject information and informed consent form (for publication) foraeldrefuldmagt 1
Subject information and informed consent form (for publication) Samtykkeerklring forldre og deltagere mellem 15 og 17 ar 2
Subject information and informed consent form (for publication) Samtykkeerklring unge fra 18 ar 1
Summary of Product Characteristics (SmPC) (for publication) Summary of product_Androgel 1_ Pump PI _ US 1

Application history

6 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-06-15 Denmark Acceptable
2023-09-20
 2023-09-20
2 SUBSTANTIAL MODIFICATION SM-1 2023-10-31 Denmark Acceptable
2023-11-06
 2023-11-07
3 SUBSTANTIAL MODIFICATION SM-2 2023-12-28 Denmark Acceptable
2024-01-26
 2024-01-29
4 NON SUBSTANTIAL MODIFICATION NSM-1 2024-04-19 Denmark Acceptable
2024-01-26
 2024-04-19
5 NON SUBSTANTIAL MODIFICATION NSM-2 2025-03-19 Denmark Acceptable
2024-01-26
 2025-03-19
6 SUBSTANTIAL MODIFICATION SM-3 2026-04-11 Denmark Acceptable
2026-05-29
 2026-05-29