Autoimmune DiseasesPhase 2NCT05586737
Immunomodulatory Therapy in Women With Autoimmune Premature Ovarian Insufficiency
A Phase 2 study testing Rituximab in people with Autoimmune Diseases and Premature Ovarian Insufficiency, run by Angelica Lindén Hirschberg at 1 site in Sweden.
Trial summary
Title: Effects of immunomodulatory therapy on gonadal function in women with autoimmune premature ovarian insufficiency (POI) Trial objectives and purpose: To study if rituximab therapy can improve ovarian response to gonadotropin stimulation and menstrual function in women with autoimmune POI. Read more about this study
- Who is it for?
- Ages 18 to 35 years, women only
- Conditions the study is for
- Autoimmune Diseases, Premature Ovarian Insufficiency
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteSweden
- Study dates
- 29 Apr 2019to 15 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Autoimmune premature ovarian insufficiency defined as presence of autoantibodies against 21-OH, SCC, 17-OH and/or NALP5 or other relevant autoantibodies
- 18-35 yrs of age
- Body mass index 19-30.
- In fertile females, willingness to comply with effective contraceptive methods.
- Ability to provide informed consent
Who cannot join
- Documented hypersensitivity or intolerance to rituximab
- Active, severe infection
- Severe immunosuppression
- Severe cardiac disease
- Cancer
- Benign tumours of the hypothalamus, pituitary, or ovary; ovarian enlargement or ovarian cyst
Show all 13Show fewer
- Vaginal bleeding of unknown aetiology
- Hormone replacement therapy (HRT) within four weeks prior study entry.
- Pregnant or lactating women
- Concurrent treatment with other immunosuppressive drugs
- Vaccination within 4 weeks of infusion of study medication
- Severe psychiatric disorder
- Patient with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo treatment with Rituximab.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Immunomodulatory Therapy on Gonadal Function in Women With Autoimmune Premature Ovarian Insufficiency
Title: Effects of immunomodulatory therapy on gonadal function in women with autoimmune premature ovarian insufficiency (POI)
Trial objectives and purpose: To study if rituximab therapy can improve ovarian response to gonadotropin stimulation and menstrual function in women with autoimmune POI.
Read more
Treatment: Controlled ovarian hyperstimulation before and four months after an infusion of 1-gram rituximab (Mabthera®) twice with two weeks interval. Follow-up period 12 months after infusion.
Primary outcome: Number of antral follicles and the size of the largest follicle in response to ovarian stimulation.
Secondary outcomes:
- Reestablishment of spontaneous menstrual bleedings during the 12 months' study period
- Ovulation during the 12 months' study period
- Change in B-cell count, autoantibody indices and immunoglobulin levels (IgG) after treatment
Safety outcomes: All adverse events. Of particular relevance are any hospital admissions, infections and allergic reactions.
Study population: Fifteen women with autoimmune POI defined as absence of menstruation > 6 months and elevated serum level of follicle stimulation hormone > 40 International units (IU)/L.
Inclusion criteria: Autoimmune POI defined as presence of autoantibodies against 21-hydroxylase (OH), side chain cleavage enzyme (SCC), 17-OH and/or neuronal apoptosis inhibitory protein (NACHT) leucine-rich-repeat protein 5 (NALP5) or other relevant autoantibodies; 18-35 yrs of age; body mass index 19-30.
Exclusion criteria: Hypersensitivity to rituximab; severe infection; severe immunosuppression; cardiac disease; cancer; benign tumours of the hypothalamus, pituitary, or ovary; ovarian enlargement or ovarian cyst; vaginal bleeding of unknown aetiology.
Time plan: The study is expected to start the spring 2017. It is expected to be closed spring 2023.
- Being tested
- Rituximab
- Medical subject headings
- Autoimmune Diseases, Primary Ovarian Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
1 gram rituximab twice with two weeks interval
| Study group | Role | What they receive |
|---|---|---|
| rituximab | Experimental | Controlled ovarian hyperstimulation will be performed before and four months after two infusions of 1-gram rituximab (Mabthera®). Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of antral follicles in response to ovarian stimulation 4 months after last rituximab infusion.
Vaginal ultrasound measurement
Measured: 4 months
The largest follicle in response to ovarian stimulation 4 months after last rituximab infusion.
Vaginal ultrasound measurement
Measured: 4 months
Secondary outcomes (3)
Spontaneous menstrual bleedings during the 12 months' study period
Number of spontaneous menstrual bleedings
Measured: 12 months
Ovulation during the 12 months' study period
Confirmed ovulation (y/n)
Measured: 12 months
Immunoglobulin levels
Change in immunoglobulin levels (g/L) from baseline
Measured: 4 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2022
- Study start29 Apr 2019
- Primary completion15 Dec 2024
- Study completion15 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Autoimmune DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Angelica Lindén Hirschberg
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Angelica Lindén Hirschberg, Karolinska University Hospital
- Investigators
- Olle Kämpe, MD, PhD, Study chair, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05586737
- Sponsor's protocol ID
- KarolinskaUniversityHospital
- Status last verified
- Dec 2024
- First submitted
- 9 Oct 2022
- Last updated
- 18 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hirschberg AL, Bjornsdottir S, Gunnarsson I, Sergouniotis F, Wanggren K, Sousa Silva C, Vogt E, Oksnes M, Husebye ES, Bensing S, Kampe O. Immunotherapy for Fertility in Autoimmune Premature Ovarian Insufficiency. NEJM Evid. 2026 Jul;5(7):EVIDoa2500303. doi: 10.1056/EVIDoa2500303. Epub 2026 Jun 23.
PubMed 42334299
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Immunomodulatory Therapy on Gonadal Function in Women With Autoimmune Premature Ovarian Insufficiency
- ClinicalTrials.gov ID
- NCT05586737
- Acronym / sponsor ID
- KarolinskaUniversityHospital
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Angelica Lindén HirschbergUniversity, hospital or other
- Study start
- 29 Apr 2019 (actual)
- Primary completion
- 15 Dec 2024 (actual)
- Study completion
- 15 Dec 2024 (actual)
- First posted
- 19 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Title: Effects of immunomodulatory therapy on gonadal function in women with autoimmune premature ovarian insufficiency (POI)
Trial objectives and purpose: To study if rituximab therapy can improve ovarian response to gonadotropin stimulation and menstrual function in women with autoimmune POI.
Treatment: Controlled ovarian hyperstimulation before and four months after an infusion of 1-gram rituximab (Mabthera®) twice with two weeks interval. Follow-up period 12 months after infusion.
Primary outcome: Number of antral follicles and the size of the largest follicle in response to ovarian stimulation.
Secondary outcomes:
- Reestablishment of spontaneous menstrual bleedings during the 12 months' study period
- Ovulation during the 12 months' study period
- Change in B-cell count, autoantibody indices and immunoglobulin levels (IgG) after treatment
Safety outcomes: All adverse events. Of particular relevance are any hospital admissions, infections and allergic reactions.
Study population: Fifteen women with autoimmune POI defined as absence of menstruation > 6 months and elevated serum level of follicle stimulation hormone > 40 International units (IU)/L.
Inclusion criteria: Autoimmune POI defined as presence of autoantibodies against 21-hydroxylase (OH), side chain cleavage enzyme (SCC), 17-OH and/or neuronal apoptosis inhibitory protein (NACHT) leucine-rich-repeat protein 5 (NALP5) or other relevant autoantibodies; 18-35 yrs of age; body mass index 19-30.
Exclusion criteria: Hypersensitivity to rituximab; severe infection; severe immunosuppression; cardiac disease; cancer; benign tumours of the hypothalamus, pituitary, or ovary; ovarian enlargement or ovarian cyst; vaginal bleeding of unknown aetiology.
Time plan: The study is expected to start the spring 2017. It is expected to be closed spring 2023.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| rituximab | Experimental | Drug: RituximabControlled ovarian hyperstimulation will be performed before and four months after two infusions of 1-gram rituximab (Mabthera®). |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Autoimmune premature ovarian insufficiency defined as presence of autoantibodies against 21-OH, SCC, 17-OH and/or NALP5 or other relevant autoantibodies
- 18-35 yrs of age
- Body mass index 19-30.
- In fertile females, willingness to comply with effective contraceptive methods.
- Ability to provide informed consent
Key exclusion criteria (13 listed)
- Documented hypersensitivity or intolerance to rituximab
- Active, severe infection
- Severe immunosuppression
- Severe cardiac disease
- Cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rituximab1 gram rituximab twice with two weeks interval | Drug | rituximab |
Primary outcome
Number of antral follicles in response to ovarian stimulation 4 months after last rituximab infusion.
Time frame: 4 months
Vaginal ultrasound measurement
The largest follicle in response to ovarian stimulation 4 months after last rituximab infusion.
Time frame: 4 months
Vaginal ultrasound measurement
3 secondary outcomes
Spontaneous menstrual bleedings during the 12 months' study period
Time frame: 12 months
Ovulation during the 12 months' study period
Time frame: 12 months
Immunoglobulin levels
Time frame: 4 and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
- Derived from this study: PubMed 42334299Hirschberg AL, Bjornsdottir S, Gunnarsson I, Sergouniotis F, Wanggren K, Sousa Silva C, Vogt E, Oksnes M, Husebye ES, Bensing S, Kampe O. Immunotherapy for Fertility in Autoimmune Premature Ovarian Insufficiency. NEJM Evid. 2026 Jul;5(7):EVIDoa2500303. doi: 10.1056/EVIDoa2500303. Epub 2026 Jun 23.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olle Kämpe, MD, PhD study chair
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab in people with Autoimmune Diseases and Premature Ovarian Insufficiency, run by Angelica Lindén Hirschberg at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of antral follicles in response to ovarian stimulation 4 months after last rituximab infusion. (time frame: 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05586737, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024; AzTrials last refreshed its copy on 8 Nov 2026.