RITUXIMAB for Autoimmune premature ovarian insufficiency | Premature ovarian insufficiency

Inclusion criteria

• {"criterion_text":"-The subject has given their written consent to participate in the trial"}
• {"criterion_text":"-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)"}
• {"criterion_text":"-18-38 years of age"}
• {"criterion_text":"-Body mass index between 19-30"}
• {"criterion_text":"-Willing to use effective non-hormonal contraceptive method (such as intra uterine device (IUD), sexual abstinence, male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide) during the 18-month study period"}

Exclusion criteria

• {"criterion_text":"-Hypersensitivity to rituximab, any of the AxMPs, or any of the excipients (as detailed in the SmPC for the various IMPs)"}
• {"criterion_text":"-Concurrent treatment with other immunosuppressive drugs"}
• {"criterion_text":"-Any vaccination within 4 weeks of infusion of study medication"}
• {"criterion_text":"-Severe psychiatric disorder"}
• {"criterion_text":"-Any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo treatment with rituximab or controlled ovarian hyperstimulation"}
• {"criterion_text":"-Active, severe infection or JCV positivity"}
• {"criterion_text":"-Severe immunosuppression"}
• {"criterion_text":"-Severe cardiac disease"}
• {"criterion_text":"-Cancer"}
• {"criterion_text":"-Benign tumours of the hypothalamus, pituitary, or ovarian pathology"}
• {"criterion_text":"-Vaginal bleeding of unknown etiology"}
• {"criterion_text":"-Hormone replacement therapy within four weeks prior study entry"}
• {"criterion_text":"-Pregnant or lactating women"}
• {"criterion_text":"-Active hepatitis B infection"}
• {"criterion_text":"-Active thrombolic disorder (contraindicated for Ovirelle)"}
• {"criterion_text":"-Moderate or severe impairment of kidney or liver function (contraindicated for Orgalutran)"}

Primary endpoints

• {"endpoint_text":"-Egg retrieval (yes/no) in response to controlled ovarian hyperstimulation at 4 to 6 months post-rituximab treatment compared to placebo, as well as within the rituximab-treated group at 4 to 6 and 12 months after the last treatment session compared to baseline.","definition_or_measurement_approach":"Binary outcome (yes/no) measured as occurrence of egg retrieval after controlled ovarian hyperstimulation at specified timepoints (4-6 months post-treatment compared to placebo; and 4-6 and 12 months compared to baseline within rituximab group)."}

Secondary endpoints

• {"endpoint_text":"-Occurrence of spontaneous menstrual bleeding (yes/no) at any point during the 19-month study period.","definition_or_measurement_approach":"Binary outcome (yes/no) recorded during the 19-month study period."}
• {"endpoint_text":"-Proportion of participants who achieve ovulation (defined as serum progesterone >10 nmol/L) at any time during the study period.","definition_or_measurement_approach":"Ovulation defined as serum progesterone >10 nmol/L; proportion measured at any time during study period."}
• {"endpoint_text":"-Changes in B-cell count, auto-antibody indices, and immunoglobulin (IgG) levels from baseline to the end of the study period.","definition_or_measurement_approach":"Laboratory measurements of B-cell count, auto-antibody indices and IgG levels at baseline and at study end; change from baseline."}
• {"endpoint_text":"-Changes in serum follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) levels from baseline to the end of the study period.","definition_or_measurement_approach":"Laboratory measurements of FSH and AMH at baseline and end of study; change from baseline."}
• {"endpoint_text":"-Changes in quality of life scores, as measured by validated instruments (AddiQol, PGWB, SF-36, and MRS), from baseline to the end of the study period.","definition_or_measurement_approach":"Quality of life assessed using validated instruments (AddiQol, PGWB, SF-36, MRS); changes from baseline to end of study."}
• {"endpoint_text":"-Safety endpoint: the incidence and severity of adverse events, hospital admissions, infections, allergic reactions and over stimulation in relation to the controlled ovarian hyperstimulation.","definition_or_measurement_approach":"Safety monitoring including recording incidence and severity of adverse events, hospital admissions, infections, allergic reactions and ovarian hyperstimulation events during the study."}

Sweden

Earliest CTIS Part Ii Submission Date

22-09-2025

Latest Decision Or Authorization Date

17-10-2025

Processing Time Days

25

Number Of Sites

6

Number Of Participants

30

Primary sponsor

Full Name

Karolinska University Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Sweden