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EndometriosisEarly Phase 1NCT03991520

Pilot Study of the IL-1 Antagonist Anakinra for the Treatment of Endometriosis Related Symptoms

A Early Phase 1 study testing Anakinra 100Mg/0.67Ml Inj Syringe in people with Endometriosis and Anakinra, run by University of California, San Diego at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

All current FDA approved medications to treat endometriosis pain including danazol, GnRH agonists (Lupron, Zoladex and Synarel), GnRH antagonist (elagolix) and depo-provera prevent or contradict pregnancy. Therefore women suffering from endometriosis and trying to conceive have no medical options apart from pain meds. Read more about this study

Who is it for?
Ages 18 to 45 years, women only
Conditions the study is for
Endometriosis, Anakinra, Markers of Inflammation
What is being tested?
Anakinra 100Mg/0.67Ml Inj Syringe
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
1 siteUnited States
Study dates
16 Jun 2020to Jan 2022
Phase
Early Phase 1
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 45 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Women aged 18-45 with regular menstrual periods every 24-32 days and not lasting more than 10 days per month
  • Surgical or imaging proven endometriosis.
  • At least a moderate level of menstrual pain based on the patient reported parameters of the B\&B pain scale (>4/9) with dysmenorrhea being scored at least 2/3.
  • Willing to remain on your current method of hormone therapy for duration of study

Who cannot join

  • History of hysterectomy or oophorectomy.
  • Non-response to GnRH agonist/antagonist, DMPA, aromatase inhibitors or danazol.
  • Currently pregnant or attempting pregnancy.
  • Contraindication to anakinra.
  • Chronic kidney disease stage 4 and 5 or creatinine clearance <30mL/min/1.73m2.
  • Abnormal LFTs, CBC or serum electrolytes including estimated GFR.
  • Patient refusal.
  • Plan to receive a live vaccine

Trial locations and contacts

1 site in 1 country.

Celestine Magallanes, BS contact

8582495419

cgmagall@health.ucsd.edu

United States1 site, 1 recruiting
  • UCSD Reproductive Endocrinology

    La Jolla, California, 92037

    Celestine Magallanes, BS, 858-249-5419, cgmagall@health.ucsd.edu

    Warren Foster, PhD

    Recruiting

Other trials in United States

About this study

All current FDA approved medications to treat endometriosis pain including danazol, GnRH agonists (Lupron, Zoladex and Synarel), GnRH antagonist (elagolix) and depo-provera prevent or contradict pregnancy. Therefore women suffering from endometriosis and trying to conceive have no medical options apart from pain meds. The purpose of this pilot study is to determine whether the anti-inflammatory, IL-1 inhibitor (anakinra) reduces pelvic pain due to endometriosis without altering menstrual cycles, which is an indicator of ovulatory function. Anakinra is an FDA approved injectable medication for the treatment of rheumatoid arthritis that is pregnancy category B.

Read the detailed description

Endometriosis is a chronic inflammatory disease1 that affects 5 -10% of reproductive aged women1,2. It is characterized by the presence of uterine endometrium outside the uterus. The condition causes health distress through pelvic pain and decreased QOL. Current therapies to temporarily control symptoms include surgery as well as medical options that prevent pregnancy and have significant side-effects.3,4 The most common symptoms with endometriosis include dysmenorrhea, dyspareunia and NMPP. Ultimately these lead to a decrease in QOL. All current medical therapies to treat endometriosis pain prevent or contradict pregnancy.

Inflammation is a well-established central figure in the pathophysiology of endometriosis(1). Increasingly, data is suggesting that IL-1 is a mediator of inflammation in endometriosis (2, 3). In addition, there are data that single nucleotide polymorphisms at the IL-1A gene locus are associated with endometriosis risk (4). Hence, it is rational to assess anakinra, an IL-1 antagonist, in the control of symptoms and inflammation due to endometriosis. Therefore, we propose this pilot study testing an FDA approved medication (anakinra) to reduce IL-1 and on dysmenorrhea due to endometriosis without stopping periods (a sign of ovulation).

Anakinra is a self-administered subcutaneous injectable medication that is FDA approved for the treatment of rheumatoid arthritis. As an IL-1 antagonist, it works by decreasing inflammation and is administered daily by the patient. Because Anakinra interferes with the immune system functioning, the major concern with the use of Anakinra is reduced resistance to infection. Others include injection site reactions such as redness, itching, rash, and pain. Bruising or bleeding also can occur, but it is rare. These effects usually stop after one - two weeks. Headaches and low white blood cell counts can also occur, but these are very rare. Anakinra should be used with caution in those with chronic kidney disease.

Anakinra is not specifically FDA approved for endometriosis. Although no data on its use in women with endometriosis have been published, there is no reason to expect women with endometriosis would be at any particular or increased risk than those in the general population.

This study is a randomized, double blinded, placebo controlled, cross-over clinical pilot study of 20 women. Patients diagnosed with surgical or imaging-technique proven endometriosis will be randomized to either treatment with an FDA approved medication (Anakinra) or a placebo. This is an investigator initiated single center study sponsored by the Swedish Orphan Biovitrum (SOBI). SOBI will provide the study drug and placebo.

Being tested
Anakinra 100Mg/0.67Ml Inj Syringe, Placebo
Medical subject headings
Endometriosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anakinra 100Mg/0.67Ml Inj SyringeDrug

    Also called Kineret

    The study drug is100mg/day Anakinra, which is the standard, FDA approved dose for the treatment of rheumatoid arthritis. The randomized treatment will be self-administered by the subject each evening by subcutaneous injection.

  • PlaceboDrug

    The placebo is comparable to the anakinra formulation without the active medication - a solution (pH 6.5) containing anhydrous citric acid (1.29 mg), disodium EDTA (0.12 mg), polysorbate 80 (0.70 mg), and sodium chloride (5.48 mg) in water for injection

Study groups in NCT03991520
Study groupRoleWhat they receive
Active Treatment with AnakinraExperimental10 subjects will be enrolled in this group. Initial treatment will consist of 100mg/day Anakinra, which is the standard, FDA approved dose for the treatment of rheumatoid arthritis. The randomized treatment will be self-administered by the subject each evening by subcutaneous injection from within 24 hours of the onset of menses until within 24 hours of last menstrual day.
Receives: Drug: Anakinra 100Mg/0.67Ml Inj Syringe
Standard ComparisonPlacebo comparator10 subjects will be enrolled in this group. This group will be given placebo injections as their initial treatment. The placebo is comparable to the anakinra formulation without the active medication - a solution (pH 6.5) containing anhydrous citric acid (1.29 mg), disodium EDTA (0.12 mg), polysorbate 80 (0.70 mg), and sodium chloride (5.48 mg) in water for injection. These individuals will self-administer the placebo each evening by subcutaneous injection from within 24 hours of the onset of menses until within 24 hours of last menstrual day.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Comparison of the impact of anakinra versus placebo on menstrual pain (dysmenorrhea) using the modified Biberoglu and Behrman scale.

    The primary pain outcome measure is to determine the impact of anakinra on dysmenorrhea due to endometriosis, using the modified Biberoglu and Behrman scale. The modified Biberoglu and Behrman scale consists of three patient-reported symptoms (dysmenorrhea, dyspareunia, and non-menstrual pelvic pain). Each of these is separately graded on a scale from 0 to 3, with a max of 9 and higher numbers indicating more severe symptoms. Changes in dysmenorrhea is the primary endpoint.

    Measured: Subjects will complete the baseline questionnaire at Visit 1. Subjects will fill out monthly questionnaires after the administration of either anakinra or placebo during 6 menstrual periods.

Secondary outcomes (3)
  1. Comparison of the impact of anakinra versus placebo on dyspareunia and non menstrual pelvic pain using the modified Biberoglu and Behrman scale.

    Secondary pain outcome measures are to determine the impact of anakinra on dyspareunia and non-menstrual pelvic pain due to endometriosis, using the modified Biberoglu and Behrman scale. The modified Biberoglu and Behrman scale consists of three patient-reported symptoms (dysmenorrhea, dyspareunia, and non-menstrual pelvic pain). Each of these is separately graded on a scale from 0 to 3, with a max of 9 and higher numbers indicating more severe symptoms. Changes in dyspareunia and non-menstrual pelvic pain are secondary pain endpoints.

    Measured: Subjects will complete the baseline questionnaire at Visit 1. Subjects will fill out monthly questionnaires after the administration of either anakinra or placebo during 6 menstrual periods.

  2. Comparison of the impact of anakinra versus placebo on the quality of life using the Endometriosis Health Profile 30 questionnaire (EHP-30), conducted after each course of study medication administration.

    The secondary outcome measure is to determine the impact of anakinra on the quality of life due to endometriosis, using the Endometriosis Health Profile 30 (EHP-30) questionnaire. The EHP-30 consists of a 30 item instrument that assesses pain, control and powerlessness, social support, emotional well-being, and self image. Each scale is standardized on a scale of 0 - 100, where 0 indicates the best health status through to 100 worst health status.

    Measured: Subjects will complete the baseline questionnaire at Visit 1. Subjects will fill out monthly questionnaires after the administration of either anakinra or placebo during 6 menstrual periods.

  3. Comparison of serum inflammatory markers before and after anakinra administration.

    The secondary outcome is to evaluate the effect of anakinra on serum inflammatory markers that are elevated in women with endometriosis. Relevant inflammatory markers of endometriosis include CRP, CA125, IL-1, IL-4, IL-6, IL-10, BDNF, Glycodelin, and ZAG. There will be blood tests at the start and end of each of of the subject's next 6 menstrual periods: At the time of each blood draw, we will collect 20 mL (approximately 4 teaspoons) of blood. This will be needed for each of the 6 study menstrual periods for a total of 12 blood draws. There will be a total of 240 ml of blood or approximately 16 tablespoons of blood collected throughout the entire study.

    Measured: There will be blood tests at the start and end of each of of the subject's next 6 menstrual periods for a total of 12 blood draws.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jun 2019
  2. Study start16 Jun 2020
  3. Primary completionJan 2022 (estimated)
  4. Study completionJan 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03991520
Sponsor's protocol ID
182006
Status last verified
May 2021
First submitted
27 May 2019
Last updated
28 May 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Only the PI, Dr. Foster and the study staff will have access to study subjects' research data.

Publications

  • Kennedy S, Bergqvist A, Chapron C, D'Hooghe T, Dunselman G, Greb R, Hummelshoj L, Prentice A, Saridogan E; ESHRE Special Interest Group for Endometriosis and Endometrium Guideline Development Group. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 2005 Oct;20(10):2698-704. doi: 10.1093/humrep/dei135. Epub 2005 Jun 24.

    PubMed 15980014
  • Khanaki K, Nouri M, Ardekani AM, Ghassemzadeh A, Shahnazi V, Sadeghi MR, Darabi M, Mehdizadeh A, Dolatkhah H, Saremi A, Imani AR, Rahimipour A. Evaluation of the relationship between endometriosis and omega-3 and omega-6 polyunsaturated fatty acids. Iran Biomed J. 2012;16(1):38-43. doi: 10.6091/ibj.1025.2012.

    PubMed 22562031
  • Marik JJ. Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Obstet Gynecol. 1998 May;91(5 Pt 1):793-4. doi: 10.1097/00006250-199805000-00029. No abstract available.

    PubMed 9572232
  • Stratton P, Sinaii N, Segars J, Koziol D, Wesley R, Zimmer C, Winkel C, Nieman LK. Return of chronic pelvic pain from endometriosis after raloxifene treatment: a randomized controlled trial. Obstet Gynecol. 2008 Jan;111(1):88-96. doi: 10.1097/01.AOG.0000297307.35024.b5.

    PubMed 18165396

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Anakinra 100Mg/0.67Ml Inj Syringe in people with Endometriosis and Anakinra, run by University of California, San Diego at 1 site in United States.

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 4 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 28 May 2021. 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 United States. 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. Some participants in this study may receive a placebo. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Celestine Magallanes, BS (8582495419, cgmagall@health.ucsd.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Comparison of the impact of anakinra versus placebo on menstrual pain (dysmenorrhea) using the modified Biberoglu and Behrman scale. (time frame: Subjects will complete the baseline questionnaire at Visit 1. Subjects will fill out monthly questionnaires after the administration of either anakinra or placebo during 6 menstrual periods.). 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 NCT03991520, which also lists 4 linked publications.

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 28 May 2021.

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