Treatment With the Anti-IgE Monoclonal Antibody Omalizumab in Women With Asthma Undergoing Fertility Treatment. - A Proof of Concept Study.

• Status: Recruiting
• Trial end date: 2021-04-01
• Target enrollment: 0
• Participant gender: Female

Summary

The investigators have previously confirmed a clinical hunch that women with asthma have difficulties in becoming pregnant. The investigators found increased time to pregnancy (TTP) in women with asthma compared to non-asthmatic women (55 vs 33 months, p<0.001), furthermore, women with asthma had less successful pregnancies following fertility treatment (39.6 vs 60.4%, p=0.002). Treatment with omalizumab stabilizes the eosinophilic disease, through the systemic and most likely the anti-inflammatory pathways, which indicate a promising possibility to increase pregnancy rate. In a small real-life study in 2017, 5 patients with eosinophilic asthma who underwent in vitro fertilization (IVF), were treated with omalizumab prior to embryo transplantation; three out of the five women became pregnant. Lastly, the two remaining patients had several treatments with omalizumab, but did not become pregnant. This real-life study calls for further investigation. By targeting systemic inflammation with omalizumab treatment the aim is to increase asthma control before and during pregnancy. A treatment strategy aiming at improving overall inflammatory control may increase fertility, but also reduce well known maternal and perinatal adverse pregnancy outcomes such as pregnancy loss, preeclampsia, gestational diabetes, low-birth weight, small for gestational age (SGA), preterm delivery.

Study design:

A randomized control trial with omalizumab and placebo, stratified for blood eosinophil count, is therefore needed. A randomized, double blinded, parallel group, study to evaluate the difference between omalizumab (O) and placebo (P) on pregnancy rate in patients with atopic asthma.Treatment schedule: After collection of material (blood samples, sputum, secretion of the vagina, secretion of the rectum, microbiota) 6th day (±1 day) of the menstrual cycle, the patients will be randomized in either the omalizumab group or the placebo group. No collection of material will be done at the time of enrollment, as this will be on different time of the female cycles. The treatment is initiated with one injection with weight and serum-immunglobulin E balanced omalizumab or one injection placebo. After omalizumab treatment at ovulation it will again be collected material (blood samples, sputum, secretion of the vagina, secretion of the rectum, secretion of the uterus, microbiota). If no pregnancy has occurred after first IVF cycle, this will be repeated for 3 consecutive IVF cycles in total or until pregnancy has occurred.

Outcome:

The primary out-come is efficacy of omalizumab, compared to placebo, in increasing pregnancy rate in females with asthma. Secondary out-comes are changes in the inflammation in lungs/systemic/uterus, change in microbiota in the uterus and lungs, pregnancy loss, asthma control and biomarkers in the blood/lungs/uterus.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bispebjerg Hospital; Rigshospitalet, Denmark
• Collaborators: Herlev Hospital; Hvidovre University Hospital; Novartis
• Treatments: Omalizumab

Criteria

Inclusion Criteria:

• Informed consent

• Diagnosis of asthma

• Infertility due to male factor infertility, tubal factor infertility or unexplained infertility.

• Referred to IVF treatment with or without ICSI

• Willingness to receive treatment with biologic drugs during menstruation period

• Controlled disease with an ACQ ≤ 1.5

Exclusion criteria:

• Other respiratory diseases than asthma

• Other inflammatory disease or a disease that affects fertility.

• Allergy to the investigational drugs

• Respiratory infections requiring antibiotics or anti-viral treatment within 30 days

• Current smokers and tobacco consumption more than 10 pack years.

• TESA / TESE, PCOS, endometriosis

• Infertility due to other reasons than male factor, tubal factor or unexplained infertility