About this trial
Several autoimmune diseases such as Addison's disease are associated with failing ovarian function, known as premature ovarian insufficiency (POI), which can lead to early menopause and reduced fertility.The underlying cause of POI in these women is considered to be an immunological attack on the ovaries that causes them to not respond to hormonal stimulation from the brain. Hormone replacement effectively counteracts menopausal symptoms, but today there is no treatment to normalize or even improve fertility. As a patient with POI and an autoimmune diagnosis and the desire to become pregnant, you are asked to participate in the study. The aim of this study is to investigate whether immunomodulatory therapy can improve and ideally normalize ovarian function in women of childbearing age with autoimmune disease and proven POI. Patients with a male partner and a desire for children and who respond positively to the first ovarian stimulation will be offered in vitro fertilization (IVF) and will thus be allowed to complete the study. Other participating patients will undergo a total of three ovarian stimulations and treatment with first two infusions of the registered drug rituximab or placebo (inactive agent) and later two additional infusions where all patients receive rituximab. The first two infusions with rituximab or placebo are double-blind, which means that neither you nor the study staff know what you have received. Follow-up takes place up to 12 months after the last infusion.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
The subject has given their written consent to participate in the trial
Autoimmune POI (FSH > 25 IU/L) including the presence of oligo/amenorrhea lasting at least 4 months, and elevated FSH levels (FSH > 25 IU/L) confirmed on two separate occasions, with measurements taken at least 4 weeks apart and Addison's disease or ab positivity for 21-hydroxylase or other relevant autoantibodies (SCC, 17-OH, NALP5)
18-38 years of age
Body mass index between 19-30
Disqualifiers
Hypersensitivity to rituximab, any of the AxMPs, or any of the excipients (as detailed in the SmPC for the various IMPs)
Active, severe infection or JCV positivity
Active hepatitis B infection
Severe immunosuppression
Trial design
Crossover
Treatments tested in this trial
Rituximab (Arm A)
DrugTotal 4 infusions (4 g) of Rituximab
Rituximab (Arm B)
Drug2 infusions (2 g) of Rituximab
Treatment groups
Trial outcomes
Primary outcomes
Egg retrieval in response to controlled ovarian hyperstimulation
Egg retrieval (yes/no) in response to controlled ovarian hyperstimulation at 4 to 6 months after rituximab treatment compared to placebo.
Secondary outcomes
Occurrence of spontaneous menstrual bleeding
Occurrence of spontaneous menstrual bleeding (yes/no) at any point during the 19-month study period.
Proportion of participants who achieve ovulation
Proportion of participants who achieve ovulation (defined as serum progesterone \>10 nmol/L) at any time during the study period.
Changes in serum follicle-stimulating hormone
Changes in serum follicle-stimulating hormone (FSH) IE/L levels from baseline to the end of the study period.
Change in serum anti-Mullerian hormone
Changes in serum anti-Mullerian hormone (AMH) microgram/L levels from baseline to the end of the study period.
Sponsors and contacts
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Angelica Lindén Hirschberg
Lead sponsor
Karolinska University Hospital
Sponsor institution