Efficacy of certolizumab in women with unexplained recurrent implantation failure: a double-blind randomized controlled trial (CERTIFY)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Decision date (initial)

2024-11-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511869-11-00

EudraCT number

2021-005309-28

ClinicalTrials.gov

NCT05930613

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate the efficacy of certolizumab compared to placebo on clinical pregnancy rate in women with unexplained recurrent implantation failure.

Secondary objectives 4

1. To evaluate the efficacy of certolizumab compared to placebo in women with unexplained recurrent implantation failure in terms of:
2. - live-birth rate
3. - miscarriage rate
4. To evaluate the safety of certolizumab in women with unexplained recurrent implantation failure

Conditions and MedDRA coding

Adult women with recurrent implantation failures (RIF)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Women aged 18-40 years
2. Idiopathic, male or tubal factor infertility
3. Unexplained recurrent implantation failure defined as consecutive failure to obtain clinical pregnancy after at least transfers of 3 good-quality embryos (Istanbul criteria)
4. Affiliation to a French social security system (beneficiary or legal)
5. Informed and signed consent

Exclusion criteria 35

1. Known cause of RIF among the following:
2. - Genetic parental anomalies
3. - Non-gestational diabetes mellitus of type I and II
4. - Infectious disease
5. - Antiphospholipid syndrome
6. - Sickle cell disease
7. - Diffuse adenomyosis
8. - No contraindication to Freeze-thaw embryo transfer (FET) treatment
9. Linked to certolizumab:
10. - Hypersensitivity to the active substances or to any of the excipients
11. - Primary or secondary immunodeficiency (history of or currently active)
12. - Active uncontrolled infection
13. - Active tuberculosis
14. - Cardiac insufficiency (moderate to severe, NYHA III/IV classes)
15. - Any malignant neoplasm except adequately treated basal or squamous cell carcinoma of the skin
16. - Immunization with a live/ attenuated vaccine within 4 weeks prior to baseline or simultaneously with treatment
17. - Cytopenia as defined by platelet count < 100 × 109/L (100,000/mm3), hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L), absolute neutrophil count < 2.0 × 109/L (2000/mm3), lymphocyte count < 0.5 × 109/L (500/mm3)
18. - Liver cytolysis (AST / ALT > 5 N)
19. - Insufficient kidney function, as defined by a serum creatinine of more than 260 µmol/L or creatinine clearance of 20 ml/min or less
20. - Demyelinating neurological disease
21. Linked to rifampicin and isoniazid (RIFINAH®):
22. - Hypersensitivity to the active substances or to any of the excipients
23. - Porphyria
24. - Decreased blood-clotting from low vitamin K
25. - Liver cytolysis (AST / ALT >5 N)
26. - Combination with bictegravir, cobicistat, daclatasvir, dasabuvir, delamanid, grazoprevir / elbasvir, protease inhibitors boosted by ritonavir, isavuconazole, ledipasvir, lurasidone, midostaurine, ombitasvir / paritaprévir, praziquantel, rilpivirine, sofosbuvir, velpatasvir, voriconazole, voxilaprevir
27. - Acute hepatitis, hepatic failure or chronic hepatic disease
28. - Acute nephropathy
29. Linked to anti-pneumoccal vaccination:
30. - Hypersensitivity to the active substances or to any of the excipients
31. Other exclusion criteria:
32. - Absence of health insurance (include AME)
33. - Subject under guardianship or curatorship
34. - Subject deprived of their liberty by a judicial or administrative decision
35. - Participation in another interventional study or being in the exclusion period at the end of a previous study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clinical pregnancy defined as the presence of cardiac activity on ultrasound scan at 5 weeks +/- 6 days of gestation (post-implantation)

Secondary endpoints 9

1. Live-birth
2. Miscarriage defined as spontaneous abortion or pregnancy stop before 12 weeks of gestation (post-implantation)
3. All adverse events distinguishing serious adverse events. We will particularly evaluate:
4. - multiple pregnancies
5. - ectopic pregnancy
6. - fetal abnormalities
7. - small for gestational age
8. - intrauterine growth restriction
9. - preeclampsia

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Nathalie CHABERT-BUFFET

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Nathalie CHABERT-BUFFET

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Results and documents

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

Documents 7 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