Efficacy of Rituximab in Restoring Ovarian Function in Autoimmune Premature Ovarian Insufficiency: A Double-Blind, Placebo-Controlled, Randomized Trial

The primary objective of this study is to evaluate the efficacy of rituximab in facilitating egg retrieval following controlled ovarian hyperstimulation in patients diagnosed with autoimmune premature ovarian insufficiency. The assessment compares the success of egg retrieval 4 to 6 months post-treatment between the rituximab and placebo groups, while also evaluating the entire treated cohort at 4 to 6 and 12 months relative to baseline. 5

Secondary objectives include the assessment of:

• Occurrence of spontaneous menstrual bleeding and incidence of ovulation, confirmed via serum progesterone levels.
• Changes in B-cell count, auto-antibody indices, immunoglobulin levels, follicle-stimulating hormone, and anti-Müllerian hormone.
• Variations in quality of life measured by validated instruments such as the Menopause Rating Scale.
• Safety parameters, including the monitoring of adverse events, infections, allergic reactions, and overstimulation.

The sponsor did not provide information regarding the total number of participants. The study population consists of female patients diagnosed with autoimmune premature ovarian insufficiency. Eligible participants are between 18 and 38 years of age with a body mass index ranging from 19 to 30. Inclusion requires the presence of oligoamenorrhea for a minimum of 4 months and follicle-stimulating hormone levels exceeding 25 IU/L confirmed on two separate occasions at least 4 weeks apart. Additional diagnostic requirements include Addison’s disease or positivity for 21-hydroxylase or other relevant autoantibodies, such as SCC, 17-OH, or NALP5. Participants must agree to utilize effective non-hormonal contraception throughout the 18-month study duration.

This double-blind, placebo-controlled, randomized study is designed to evaluate the efficacy of rituximab in restoring ovarian function for women diagnosed with autoimmune premature ovarian insufficiency. The research methodology focuses on the ability of the investigational product to enable egg retrieval following controlled ovarian hyperstimulation. The clinical trial protocol includes a screening phase to confirm eligibility based on follicle-stimulating hormone levels, menstrual history, and the presence of specific autoantibodies. Following enrollment, participants receive either rituximab or a placebo via infusion. Assessment of the primary endpoint occurs between 4 to 6 months and at 12 months post-treatment to compare outcomes against placebo and baseline measurements. The total period of participant involvement is approximately 19 months, during which secondary endpoints such as spontaneous menstrual bleeding, ovulation rates, B-cell count, and anti-Müllerian hormone levels are monitored. The study concludes with an end-of-study visit to evaluate long-term changes in immunoglobulin levels and quality of life scores. Safety monitoring includes the assessment of adverse events, infections, and allergic reactions.

The experimental treatment consists of rituximab, provided in the pharmaceutical form PHF00230MIG. The administration involves a 1 g dose delivered via infusion.

The study utilizes a placebo as a comparator treatment in a double-blind, randomized design to evaluate the efficacy of the immunomodulatory therapy in women with autoimmune premature ovarian insufficiency.

The primary efficacy endpoint is the success of egg retrieval following controlled ovarian hyperstimulation. This will be evaluated at 4 to 6 months post-treatment in comparison to placebo, and within the treatment group at 4 to 6 and 12 months after the final administration relative to baseline.

Secondary efficacy parameters include:

• The occurrence of spontaneous menstrual bleeding during the 19-month study duration.
• The proportion of participants achieving ovulation, defined by serum progesterone levels greater than 10 nmol/L.
• Changes in B-cell count, auto-antibody indices, and immunoglobulin levels.
• Alterations in serum follicle-stimulating hormone and anti-Müllerian hormone levels.
• Changes in quality of life scores, assessed using validated instruments including AddiQol, PGWB, SF-36, and MRS.