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

NCT03991520 | Unknown Early Phase 1 FDA Drug

• 1 other identifier: 182006
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Endometriosis; Anakinra; Markers of Inflammation

Outcome Measures

Primary Outcomes (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.

  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)

• Comparison of the impact of anakinra versus placebo on dyspareunia and non menstrual pelvic pain using the modified Biberoglu and Behrman scale.

  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.

• 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.

  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.

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

  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.

Study Arms (2)

Active Treatment with Anakinra

EXPERIMENTAL

10 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.

Drug: Anakinra 100Mg/0.67Ml Inj Syringe

Standard Comparison

PLACEBO COMPARATOR

10 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.

Drug: Placebo

Interventions

Anakinra 100Mg/0.67Ml Inj Syringe DRUG

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.

Also known as: Kineret

Active Treatment with Anakinra

Placebo DRUG

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

Standard Comparison

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: The primary aim of this study is to determine the impact of anakinra on menstrual pain due to endometriosis. Therefore, only women will be eligible for this study.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

UCSD Reproductive Endocrinology

La Jolla, California, 92037, United States

RECRUITING

Related Publications (4)

• 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.

  PMID: 15980014 BACKGROUND

• 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.

  PMID: 22562031 BACKGROUND

• 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.

  PMID: 9572232 BACKGROUND

• 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.

  PMID: 18165396 BACKGROUND

MeSH Terms

Conditions

Endometriosis

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Sanjay K Agarwal, MD

  UC San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Celestine Magallanes, BS

CONTACT

8582495419; cgmagall@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director of Fertility Services

Study Record Dates

• First Submitted: May 27, 2019
• First Posted: June 19, 2019
• Study Start: June 16, 2020
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: May 28, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)