Effects of Interleukin-1 Receptor Antagonism on Hyperandrogenemia in Women With Polycystic Ovary Syndrome (FertIL)

Effects of Interleukin-1 Receptor Antagonism on Hyperandrogenemia in Women With Polycystic Ovary Syndrome - a Prospective, Interventional, Single-arm, Open-label, Proof-of-concept Study

A prospective, interventional, open-label, single-arm, proof-of-concept study: 18 women with Polycystic Ovary Syndrome (PCOS) will be treated with 100 mg of Anakinra/Kineret® for 4 weeks. 1 week after last injection patients will have a follow-up and a dexamethasone visit after a dexamethasone suppression test. Goal of this study is to investigate the effect of the Interleukin 1( IL-1) receptor antagonist Anakinra/Kineret® on laboratory and clinical features in women with PCOS.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: IL-1 receptor antagonist Anakinra

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel Endocrinology, Diabetes and Metabolism

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Informed Consent as documented by signature
• Premenopausal women aged 18 years or older
• Onset of menarche ≥5 years ago
• Diagnosis of PCOS defined by the Rotterdam criteria
• High sensitivity C-reactive protein level ≥1 mg/l

• Follicular phase of menstrual cycle as evident by

  • Serum estradiol level <200 pmol/l AND
  • Serum progesterone level <8 ng/ml
• Willingness to use non-hormonal contraceptive measures adequate to prevent becoming pregnant during the study

Exclusion Criteria:

• Intake of any testosterone level modifying drugs in the 8 weeks prior to study inclusion,
• Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to Anakinra/Kineret,
• Women who are pregnant or breast feeding,
• Female participants who are ovariectomized or hysterectomised or post-menopausal
• Known or suspected non-compliance, drug or alcohol abuse,
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Participation in another study with investigational drug within the 30 days preceding and during the present study,
• Previous enrolment into the current study,
• Enrolment of the investigator, his/her family members, employees and other dependent persons,
• Clinical signs of infection in the week before inclusion or history of a severe infection during the last 2 months,
• Potentially severe immunosuppression or intake of other immunosuppressive drugs
• Severe hematologic disease
• Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, active carcinoma),
• History of or suspected tuberculosis and/or hepatitis B/C

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: IL-1 receptor antagonist Anakinra 100 mg; Anakinra (Kineret®; r-metHuIL-1ra, Swedish Orphan Biovitrum AB) is a recombinant, non-glycosylated form of the human IL-1Ra in a 100 mg/ 0.67 ml solution for subcutaneous injection. Anakinra/Kineret® is supplied in single use prefilled glass syringes with 27 gauge needles as a sterile, clear, colorless-to-white, preservative free solution for daily s.c. administration over a time period of 28 days.

Drug: IL-1 receptor antagonist Anakinra; IL-1 receptor antagonist Anakinra is a recombinant, non-glycosylated form of the human IL-1Ra in a 100 mg/ 0.67 ml solution for subcutaneous injection. Standard dosage licensed by the FDA and European Medicines Agency (EMA) is 100 mg Anakinra daily. It is supplied in single use prefilled glass syringes with 27 gauge needles as a sterile, clear, colourless-to-white, preservative free solution for daily s.c. administration.; Other Names: Kineret

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in fasting serum androstenedione level (nmol/l) from start (baseline, day 1) to one week after treatment start with Anakinra.	Absolute change in fasting serum androstenedione level (nmol/l) from start (baseline, day 1) to one week after treatment start with Anakinra.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ferriman-Gallwey-score	Effect of Anakinra/Kineret® on hirsutism by Ferriman-Gallwey-score (representation of hair growth in a male pattern on a woman shown in four different degrees of severity ( 0= no hair growth; 1= light hair growth; 2= moderate hair growth; 4= severe hair growth) in 11 different body parts; namely the upper lip, chin, chest, upper back, lower back, upper abdomen, lower abdomen, arm, forearm, thigh, and lower leg) will be assessed	Day 1 and 28
Sebum production measures	Effect of Anakinra/Kineret® on sebum production will be assessed with Sebumeter® SM 815, Courage + Khazaka electronic Gesellschaft mit beschränkter Haftung (GmbH)	At day 1 and 28
Self-reported frequency of hair removal (times/week)	Effect of Anakinra/Kineret® on hirsutism will be assessed	At day 1 and 28
Plewig-Kligman-score	Effect of Anakinra/Kineret® on acne severity, assessed with Plewig-Kligman score (presentation of comedonal and inflammatory acne severity, separately graded based on the number of lesions and type; lesion counting done at right side of the face, excluding other side, chest and back.	At day 1 and 28
Ovulation and menstruation rates [%]	Effect of Anakinra/Kineret® on ovulation and menstruation rates will be assessed	Between day 1 and day 35
Estradiol (pmol/l), free testosterone (nmol/l), total testosterone (nmol/l), sex hormone-binding globulin (SHBG) [nmol/l], Anti-Muellerian Hormone [pmol/l], dehydroepiandrosterone (DHEA) [nmol/l]), basal cortisol (nmol/l)	Effect of Anakinra/Kineret® on peripheral (sexual) hormones will be assessed	Day 1, 7, 14, 21, 28 and 35
Fasting glucose (mmol/l), homeostatic model of assessment of insulin resistance (HOMA-IR)	Effect of Anakinra/Kineret® on glucose metabolism will be assessed	At day 1, 7, 14, 21, 28 and 35
Pituitary hormones (luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenocorticotropic hormone (ACTH) [IU/L])	Effect of Anakinra/Kineret® on the pituitary-gonadal axis will be assessed	Day 1, 7, 14, 21, 28 and 35
Treatment response according to a Dexamethasone suppression test	Dexamethasone suppression test will be evaluated as a predictor for treatment response	At days 35 and 36
inflammatory marker white blood cell count [x109/l],	Time course of inflammatory marker white blood cell count [x109/l] will be assessed	Day 1, 7, 14, 21, 28 and 35
inflammatory marker C reactive protein (CRP) [mg/l]	Time course of inflammatory marker CRP [mg/l] will be assessed	Day 1, 7, 14, 21, 28 and 35
inflammatory marker IL-6 [pg/ml]	Time course of inflammatory marker IL-6 [pg/ml] will be assessed	Day 1 and 28
inflammatory marker IL-1Ra [pg/ml]	Time course of inflammatory marker IL-1Ra [pg/ml] will be assessed	Day 1, 7, 14, 21, 28 and 35
Change in androstenedione level (nmol/l) from start (baseline, day 1) to days 14, 21, 28, and 35 after treatment start with Anakinra.	Change in androstenedione level (nmol/l) from start (baseline, day 1) to days 14, 21, 28, and 35 after treatment start with Anakinra.	Days 14, 21, 28, and 35 after treatment start with Anakinra
Change in 11-oxygenated androgens (e.g. 11-ketotestosterone, 11-ketoandrostenedione, 11β-hydroxytestosterone, 11β-hydroxyandrostenedione [nmol/l]) on days 7, 14, 28, and 35 after treatment start with Anakinra	Change in 11-oxygenated androgens (e.g. 11-ketotestosterone, 11-ketoandrostenedione, 11β-hydroxytestosterone, 11β-hydroxyandrostenedione [nmol/l]) on days 7, 14, 28, and 35 after treatment start with Anakinra	Days 7, 14, 28, and 35 after treatment start with Anakinra

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Mirjam Christ-Crain, Prof. Dr. MD, University Hospital Basel, Dep. of Endocrinology, Diabetes and Metabolism

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2018
• Primary Completion (Actual): July 30, 2020
• Study Completion (Actual): July 30, 2020

Study Registration Dates

• First Submitted: June 21, 2018
• First Submitted That Met QC Criteria: July 3, 2018
• First Posted (Actual): July 6, 2018

Study Record Updates

• Last Update Posted (Actual): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: androstenedione; hyperandrogenemia; Interleukin-1 receptor antagonism; Kineret/Anakinra; testosteron
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: 2018-00780; me16CC6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No