NCT05930613 Certolizumab in Recurrent Implantation Failure (RIF)

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You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

Phase 3 trials are large pivotal studies comparing the treatment to current standard of care or placebo. Your participation directly contributes to the evidence needed for regulatory approval.

This trial targets 161 participants in total. It began in 2023-11-30 with a primary completion date of 2029-04.

Brief 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.

Eligibility Criteria

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.

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