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RECRUITING

NCT05930613

PHASE3

Certolizumab in Recurrent Implantation Failure (RIF)

Sponsor: Assistance Publique - Hôpitaux de Paris

View on ClinicalTrials.gov

Summary

Recurrent implantation failure (RIF), defined as the absence of clinical pregnancy after the transfer of three good-quality embryos, concerns up to 40% of IVF couples and is associated with a low success rate. The causes remain unexplained in over 50% of cases. Various dysimmune changes (related to immune T cells profiles, pro-inflammatory cytokines levels) have been described in unexplained RIF as compared to fertile controls, and it has been estimated that such dysimmunity may occur in 50% of unexplained RIFs. Previous data on a benefit of general immune modulation by steroids or immunoglobulins are heterogenous and failed to demonstrate clinically significant benefit. The proinflammatory cytokine Tumor Necrosis Factor (TNF) α participates in the regulation of the immune balance of the endometrium, its peripheral blood and endometrial concentrations are increased in RIF patients as compared to fertile controls. In 2009, a pilot placebo controlled study showed that TNF-α antagonist treatment allowed a 56% live birth rate (versus 13% in controls) in 13 women with unexplained RIF. Due to the lack of maternal and fetal tolerance data, TNF-α antagonists were not further evaluated. Today, safety data issued from 1200 pregnancies are reassuring allowing the use of TNF-α antagonists during pregnancy (www.lecrat.org). In addition the TNF-α antagonist certolizumab does not cross the placental barrier. We hypothesize that certolizumab may improve clinical pregnancy rates in women with unexplained RIF with a good safety profile.

Official title: Efficacy of Certolizumab in Women With Unexplained Recurrent Implantation Failure: a Double-blind Randomized Controlled Trial

Key Details

Gender

FEMALE

Age Range

18 Years - 40 Years

Study Type

INTERVENTIONAL

Enrollment

161

Start Date

2023-11-30

Completion Date

2029-04

Last Updated

2023-12-11

Healthy Volunteers

Conditions

Recurrent Unexplained Implantation Failure

Interventions

DRUG

Certolizumab (CIMZIA® ; TNF-α antagonist)

400mg of certolizumab injected subcutaneously monthly from 5 weeks before embryo transfer until 7 weeks of gestation (injections at 5 and 1 week before embryo transfer, 3 and 7 weeks after embryo transfer) for a total of 4 injections in case of ongoing intrauterine pregnancy.

DRUG

Placebo (NaCl 0.9 % solution)

NaCl 0,9% injected subcutaneously monthly from 5 weeks before embryo transfer until 7 weeks of gestation (injections at 5 and 1 week before embryo transfer, 3 and 7 weeks after embryo transfer) for a total of 4 injections in case of ongoing intrauterine pregnancy.

Inclusion Criteria: * Women aged 18-40 years * Idiopathic, male or tubal factor infertility * Unexplained recurrent implantation failure defined as consecutive failure to obtain clinical pregnancy after at least transfers of 3 good-quality embryos (Istanbul criteria) * Affiliation to a French social security system (beneficiary or legal) * Informed and signed consent Exclusion Criteria: Known cause of RIF among the following: * Genetic parental anomalies * Non-gestational diabetes mellitus of type I and II, * Infectious disease * Antiphospholipid syndrome * Sickle cell disease * Diffuse adenomyosis * No contraindication to Freeze-thaw embryo transfer (FET) treatment Linked to certolizumab: * Hypersensitivity to the active substances or to any of the excipients * Primary or secondary immunodeficiency (history of or currently active) * Active uncontrolled infection * Active tuberculosis * Cardiac insufficiency (moderate to severe, New York Heart Association (NYHA) III/IV classes) * Any malignant neoplasm except adequately treated basal or squamous cell carcinoma of the skin * Immunization with a live/ attenuated vaccine within 4 weeks prior to baseline or simultaneously with treatment * 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) * Liver cytolysis (AST / ALT \> 5 N) * Insufficient kidney function, as defined by a serum creatinine of more than 3 mg/dL or creatinine clearance of 20 ml/min or less * Demyelinating neurological disease Linked to rifampicin and isoniazid (RIFINAH®) * Hypersensitivity to the active substances or to any of the excipients * Porphyria * Decreased blood-clotting from low vitamin K * Liver cytolysis (AST / ALT \>5 N) * 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 * Acute hepatitis, hepatic failure or chronic hepatic disease * Acute nephropathy Contraindication to anti-pneumococcal vaccination (Pneumovax®) \- Hypersensitivity to the active substances or to any of the excipients Other criteria: * Absence of health insurance (include AME) * Subject under guardianship or curatorship * Subject deprived of their liberty by a judicial or administrative decision * Participation in another interventional study or being in the exclusion period at the end of a previous study.

Locations (1)

Saint-Antoine Hospital - APHP

Paris, France