Extended LH administration (ELHA), a strategy to increase the pool of recruitable antral follicles: a multicentric randomized trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliero Universitaria Di Modena

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

12 Nov 2024 → ongoing

Decision date (initial)

2024-11-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Healthcare KGaA

External identifiers

EU CT number

2024-517407-36-00

EudraCT number

2022-004285-38

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective of the study is to confirm that pre-treatment with rhLH at the dose of 187.5 IU/day for 60 days can improve ovarian reserve as indicated by an increase in basal AMH.

Secondary objectives 1

1. 1. Change from baseline for basal AFC (antral follicle count) after 60 days of LH prolonged treatment or no treatment 2. Change from baseline for basal AMH after 30 days of LH prolonged treatment or no treatment 3. Change from baseline for basal AFC (antral follicle count) after 30 days of LH prolonged treatment or no treatment 4. Ovarian response to controlled ovarian stimulation in IVF/ICSI cycles (number of follicles >16 mm at the end of stimulation, number of retrieved oocytes, FORT index- follicles to oocyte ratio, number of mature oocytes) 5. Evaluate the safety of rLH throughout the treatment period 6. cycles discontinued/cancelled before rhCG administration due to poor or excessive ovarian response 7. percent of missed transfer of fresh embryos 8. implantation rate 9. biochemical pregnancy rate 10. clinical pregnancy rate 11. early (≤9 days after triggering) and late (12–17 days after triggering) OHSS onset (according to Golan’s Classification System) rate 12. miscarriage rate 13. preterm birth rate 14. low birth weight rate 15. congenital anomalies rate 16. gestational age at delivery 17. mean neonatal weight

Conditions and MedDRA coding

Patients admitted to an IVF/ICSI cycle will be included. The patient will be addresses to the IVF cycles for the following reasons: tubal factor, male factor or for idiopathic infertility.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. AFC of at least 5 in the 3 months prior to the study cycle 2. Basal AMH levels of at least 1 ng/ml in the 3 months prior to the study cycle 3. Age 25-38 at the moment of the study cycle 4. D3 Basal LH: 1-6 IU/L in the 3 months prior to the study cycle 5. D3 Basal FSH: < 8 IU/L in the 3 months prior to the study cycle 6. D3 Estradiol < 70 pg/ml in the 3 months prior to the study cycle 7. Willing to participate 8. Capable to understand and follow the study procedure 9. eumenorrheic women with low LH levels candidate to IVF/ICSI cycle for tubal factor, male factor or for idiopathic infertility 10. Acceptance and signature of the informed consent

Exclusion criteria 1

1. 1. PCOS patients according to Rotterdam’s criteria 2. Patients with irregular cycles (shorter than 25 days or longer than 35 days) 3. Patients already treated with LH priming 4. Patients planning to undergo duo/double stimulation 5. Patients with ASRM Stage III or IV endometriosis 6. Patients with prior surgery significantly affecting ovary (ie ovariectomy, cystectomy significantly reducing ovarian volume or others) as assessed by the responsible gynecologist 7. Previous cycle with less than 4 oocytes recovered 8. Patients treated with hormones in the 3 months before the study 9. Patients with an already known endocrinological disease including hypothyroidism (defined by TSH < 4 mIU/L), adrenocortical deficiency (ACTH stimulation test (250 mcg) with basal cortisol <3 mcg or, if basal cortisol is 3-18 mcg serum level, cortisol serum level 30 minutes after the stimulation test <18 mcg) and hyperprolactinemia (PLR > 25mcg/l) 10. previous episode of OHSS or exuberant ovarian response to gonadotropins 11. hypersensitivity to the study drug 12. contraindication for pregnancy 13. porphyria or a family history of porphyria 14. history of ovarian torsion 15. BMI > 30 kg/m2 16. ovarian enlargement or ovarian cyst 17. gynecological bleeding of unknown origin 18. history of ovarian, breast or endometrial cancer.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the study will be to confirm that the pre-treatment with rhLH at the dose of 187.5 IU/day for 60 days may improve ovarian reserve as indicated by an increase in basal AMH.

Secondary endpoints 1

1. • Change of AFC after 30/60 days • Change of AMH after 30 days • Ovarian response • Evaluate the safety of rLH • cycles discontinued/cancelled before rhCG administration • percent of missed transfer of fresh embryos • implantation rate • biochemical pregnancy rate • clinical pregnancy rate • early and late OHSS rate • miscarriage rate • preterm birth rate • low birth weight rate • congenital anomalies rate • gestational age at delivery • mean neonatal weight

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero Universitaria Di Modena

Sponsor organisation

Azienda Ospedaliero Universitaria Di Modena

Address

Largo Del Pozzo 71

City

Modena

Postcode

41124

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Antonio La Marca

Public contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Antonio La Marca

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 8 files

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

Application history

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