A Multicenter Randomized Controlled Trial Assessing the Efficacy and Safety of Recombinant Human Follicle Stimulating Hormone (r-hFSH-alfa originator) and Human Chorionic Gonadotropin (hCG) in Enhancing Sperm Concentration in Men with Oligozoospermia, Low Testosterone, and Normai FSH Serum Levels (APHRODITE Group 3): A Collaborative Research Initiative

2025-525005-20-00 Protocol MATES Study Therapeutic use (Phase IV) Authorised, recruitment pending

Status Authorised, recruitment pending · 3 EU/EEA countries · 7 sites · Protocol MATES Study

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Authorised, recruitment pending
Participants planned 138
Countries 3
Sites 7

Male Infertility

To assess the impact of the combined administration of r-hFSH-alfa originator plus hCG compared to no treatment on sperm concentration in men with lowered semen analysis, low testosterone serum levels and normai FSH serum levels.

Key facts

Sponsor
Martin-Luther-Universitaet Halle-Wittenberg
Participant type
Patients
Age range
18-64 years
Gender
Male
Therapeutic area
Phenomena and Processes [G] - Reproductive and Urinary Physiological Phenomena [G08]
Decision date (initial)
2026-05-19
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the impact of the combined administration of r-hFSH-alfa originator plus hCG compared to no treatment on sperm concentration in men with lowered semen analysis, low testosterone serum levels and normai FSH serum levels.

Secondary objectives 4

  1. To assess the impact of the combined administration of r-hFSH-alfa originator plus hCG compared to no treatment on the following semen parameters: total sperm count (TSC), total motile sperm count (TMSC), % progressive motile sperm and morphology normai sperm
  2. To assess the impact of the combined administration of r-hFSH-alfa originator plus hCG compared to no treatment on DNA Fragmentation Index (DFI)
  3. To assess the impact of the combined administration of r-hFSH-alfa originator plus hCG compared to no treatment on hormonal values
  4. To evaluate the safety and tolerability of the combined administration of r-hFSH-alfa originator plus hCG compared to no treatment

Conditions and MedDRA coding

Male Infertility

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

  1. Male with an age ≥ 18 years old ≤ 55 years old
  2. Male infertility of at least 12 months (ICMART definition)
  3. Sperm concentration ≥ 1 million/ml and ≤ 16 million/ml at screening
  4. Normal FSH serum levels (1.5-8 IU/mL) at screening
  5. Normal LH serum levels (at least 1.5 IU/ml) at screening
  6. Low testosterone serum levels (between 210 and 350 ng/dL, corresponding to 7.3-12.1nmol/L) at screening
  7. Normal serum prolactin and thyroid-stimulating hormone (TSH) values as measured in a local lab
  8. Have not received gonadotropin, aromatase inhibitors and SERMs at least 3 months before the start of screening
  9. No clinically significant abnormal findings in the screening haematology, biochemistry, and urinalysis parameters
  10. BMI < 35 kg/m2

Exclusion criteria 9

  1. Diagnosed genetic mutations responsible for abnormal sperm concentration (e.g., YCMD, CFTR gene mutations)
  2. Signs of testicular inflammation and or infection, as well as signs of obstruction (including testicular volume higher than 25 mL at ultrasound examination)
  3. Patients with clinical varicocele (any grade)
  4. At Screening and during the study period the presence of an uncontrolled chronic disease (ongoing acute episodes or inadequate treatments), such as diabetes mellitus, thyroid disorders, autoimmune diseases such as arthritis, vasculitis or inflammatory bowel disease
  5. Presence of active malignancies
  6. Patients with history of gonadotoxic treatments
  7. Patients that received testosterone therapy at any time during the previous 12 months of the study screening
  8. Patients with a history of anabolic steroid use
  9. Patients with one testis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The primary endpoint of the study will be the evaluation of sperm concentration (Ml/ml) on the last day of treatment (week 16) compared to the untreated arm

Investigational products

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

Test 2

GONAL-f 900 IU/1.44 mL solution for injection in pre-filled pen

PRD3311572 · Product

Active substance
Follitropin Alfa
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS INJECTION
Max daily dose
150 IU international unit(s)
Max total dose
7200 IU international unit(s)
Max treatment duration
16 Week(s)
Authorisation status
Authorised
ATC code
G03GA05 — FOLLITROPIN ALFA
Marketing authorisation
EU/1/95/001/035
MA holder
MERCK EUROPE B.V.
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

GONASI HP 250 U.I. / 1 ml polvere e solvente per soluzione iniettabile

PRD2493650 · Product

Active substance
Chorionic Gonadotrophin
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAMUSCULAR INJECTION
Max daily dose
500 IU international unit(s)
Max total dose
14000 IU international unit(s)
Max treatment duration
16 Week(s)
Authorisation status
Authorised
ATC code
G03GA01 — CHORIONIC GONADOTROPHIN
Marketing authorisation
003763289
MA holder
IBSA FARMACEUTICI ITALIA
MA country
Italy
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Martin-Luther-Universitaet Halle-Wittenberg

6 Total trials 2 Recruiting 3 Ended
Academic / Non-commercial
Sponsor organisation
Martin-Luther-Universitaet Halle-Wittenberg
Address
Ernst-Grube-Strasse 40, Kroellwitz Kroellwitz
City
Halle (Saale)
Postcode
06120
Country
Germany

Scientific contact point

Organisation
Martin-Luther-Universitaet Halle-Wittenberg
Contact name
Center for Reproductive Medicine and Andrology

Public contact point

Organisation
Martin-Luther-Universitaet Halle-Wittenberg
Contact name
Benedetta Porro

Third parties 1

OrganisationCity, countryDuties
Gb Pharma S.r.l.
ORG-100001300
 Milan, Italy On site monitoring, Code 10, Code 5, Data management, E-data capture, Code 8

Locations

3 EU/EEA countries · 7 investigational sites

By country

CountryMS statusPlanned subjectsSites
Germany Authorised, recruitment pending 60 3
Italy Authorised, recruitment pending 39 2
Spain Authorised, recruitment pending 39 2
Rest of world — 0 —

Investigational sites

Germany

3 sites · Authorised, recruitment pending
Martin-Luther-Universitaet Halle-Wittenberg
Center for Reproductive Medicine and Andrology, Ernst-Grube-Strasse 40, Kroellwitz, Halle (Saale)
Universitaetsklinikum Muenster AöR
Andrology, Albert-Schweitzer-Campus 1, Sentrup, Muenster
Justus-Liebig-Universitaet Giessen
Dept. Of Urology, Pediatric Urology and Andrologie Giessen, Rudolf-Buchheim-Strasse 7, 35392, Giessen

Italy

2 sites · Authorised, recruitment pending
Azienda Ospedaliera di Padova
U.O.C. Andrologia e Medicina della Riproduzione, Via Nicolo' Giustiniani 2, 35128, Padova
Azienda Sanitaria Locale Roma 2
UOC Reproductive Physiopathology and Andrology, Via Dei Monti Tiburtini 385, 00157, Rome

Spain

2 sites · Authorised, recruitment pending
Ivi Valencia S.L.
NA (Assisted Reproduction and Fertility Clinic), Placa Policia Local 3, 46015, Valencia
Ivi Madrid S.L.
NA (Assisted Reproduction and Fertility Clinic), Avenida Talgo 68-70, 28023, Madrid

Results and documents

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

Documents 22 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol 2025-525005-20-00_redacted 1
Protocol (for publication) D4_Patient facing document_questionnaire AMS_DE 1
Protocol (for publication) D4_Patient facing document_questionnaire AMS_ES 1
Protocol (for publication) D4_Patient facing document_questionnaire AMS_IT 1
Protocol (for publication) D4_Patient manual DE 1
Protocol (for publication) D4_Patient manual EN 1
Protocol (for publication) D4_Patient manual ES 1
Protocol (for publication) D4_Patient manual IT 1
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_SIS and ICF participants_DE 2
Subject information and informed consent form (for publication) L1_SIS and ICF participants_ES 3
Subject information and informed consent form (for publication) L1_SIS and ICF participants_IT 3
Subject information and informed consent form (for publication) L2_Privacy IT 2
Subject information and informed consent form (for publication) L3_GP Letter_IT 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC GONALf 900 IU 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC GONASI HP 1
Synopsis of the protocol (for publication) D1_Protocol synopsis 2025-525005-20-00_DE 1
Synopsis of the protocol (for publication) D1_Protocol synopsis 2025-525005-20-00_EN 1
Synopsis of the protocol (for publication) D1_Protocol synopsis 2025-525005-20-00_ES 1
Synopsis of the protocol (for publication) D1_Protocol synopsis 2025-525005-20-00_IT 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2026-01-30 Germany Acceptable
2026-05-18
 2026-05-18

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