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

Primary Purpose

Polycystic Ovary Syndrome

Status
Completed
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
IL-1 receptor antagonist Anakinra
Sponsored by
University Hospital, Basel, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycystic Ovary Syndrome focused on measuring Interleukin-1 receptor antagonism, Kineret/Anakinra, testosteron, hyperandrogenemia, androstenedione

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • University Hospital Basel Endocrinology, Diabetes and Metabolism

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IL-1 receptor antagonist Anakinra 100 mg

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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)
Self-reported frequency of hair removal (times/week)
Effect of Anakinra/Kineret® on hirsutism will be assessed
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.
Ovulation and menstruation rates [%]
Effect of Anakinra/Kineret® on ovulation and menstruation rates will be assessed
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
Fasting glucose (mmol/l), homeostatic model of assessment of insulin resistance (HOMA-IR)
Effect of Anakinra/Kineret® on glucose metabolism will be assessed
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
Treatment response according to a Dexamethasone suppression test
Dexamethasone suppression test will be evaluated as a predictor for treatment response
inflammatory marker white blood cell count [x109/l],
Time course of inflammatory marker white blood cell count [x109/l] will be assessed
inflammatory marker C reactive protein (CRP) [mg/l]
Time course of inflammatory marker CRP [mg/l] will be assessed
inflammatory marker IL-6 [pg/ml]
Time course of inflammatory marker IL-6 [pg/ml] will be assessed
inflammatory marker IL-1Ra [pg/ml]
Time course of inflammatory marker IL-1Ra [pg/ml] will be assessed
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.
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

Full Information

First Posted
June 21, 2018
Last Updated
January 26, 2021
Sponsor
University Hospital, Basel, Switzerland
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1. Study Identification

Unique Protocol Identification Number
NCT03578497
Brief Title
Effects of Interleukin-1 Receptor Antagonism on Hyperandrogenemia in Women With Polycystic Ovary Syndrome
Acronym
FertIL
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
August 31, 2018 (Actual)
Primary Completion Date
July 30, 2020 (Actual)
Study Completion Date
July 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland

4. Oversight

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

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome
Keywords
Interleukin-1 receptor antagonism, Kineret/Anakinra, testosteron, hyperandrogenemia, androstenedione

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IL-1 receptor antagonist Anakinra 100 mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
IL-1 receptor antagonist Anakinra
Other Intervention Name(s)
Kineret
Intervention Description
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.
Primary Outcome Measure Information:
Title
Absolute change in fasting serum androstenedione level (nmol/l) from start (baseline, day 1) to one week after treatment start with Anakinra.
Description
Absolute change in fasting serum androstenedione level (nmol/l) from start (baseline, day 1) to one week after treatment start with Anakinra.
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Ferriman-Gallwey-score
Description
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
Time Frame
Day 1 and 28
Title
Sebum production measures
Description
Effect of Anakinra/Kineret® on sebum production will be assessed with Sebumeter® SM 815, Courage + Khazaka electronic Gesellschaft mit beschränkter Haftung (GmbH)
Time Frame
At day 1 and 28
Title
Self-reported frequency of hair removal (times/week)
Description
Effect of Anakinra/Kineret® on hirsutism will be assessed
Time Frame
At day 1 and 28
Title
Plewig-Kligman-score
Description
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.
Time Frame
At day 1 and 28
Title
Ovulation and menstruation rates [%]
Description
Effect of Anakinra/Kineret® on ovulation and menstruation rates will be assessed
Time Frame
Between day 1 and day 35
Title
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)
Description
Effect of Anakinra/Kineret® on peripheral (sexual) hormones will be assessed
Time Frame
Day 1, 7, 14, 21, 28 and 35
Title
Fasting glucose (mmol/l), homeostatic model of assessment of insulin resistance (HOMA-IR)
Description
Effect of Anakinra/Kineret® on glucose metabolism will be assessed
Time Frame
At day 1, 7, 14, 21, 28 and 35
Title
Pituitary hormones (luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenocorticotropic hormone (ACTH) [IU/L])
Description
Effect of Anakinra/Kineret® on the pituitary-gonadal axis will be assessed
Time Frame
Day 1, 7, 14, 21, 28 and 35
Title
Treatment response according to a Dexamethasone suppression test
Description
Dexamethasone suppression test will be evaluated as a predictor for treatment response
Time Frame
At days 35 and 36
Title
inflammatory marker white blood cell count [x109/l],
Description
Time course of inflammatory marker white blood cell count [x109/l] will be assessed
Time Frame
Day 1, 7, 14, 21, 28 and 35
Title
inflammatory marker C reactive protein (CRP) [mg/l]
Description
Time course of inflammatory marker CRP [mg/l] will be assessed
Time Frame
Day 1, 7, 14, 21, 28 and 35
Title
inflammatory marker IL-6 [pg/ml]
Description
Time course of inflammatory marker IL-6 [pg/ml] will be assessed
Time Frame
Day 1 and 28
Title
inflammatory marker IL-1Ra [pg/ml]
Description
Time course of inflammatory marker IL-1Ra [pg/ml] will be assessed
Time Frame
Day 1, 7, 14, 21, 28 and 35
Title
Change in androstenedione level (nmol/l) from start (baseline, day 1) to days 14, 21, 28, and 35 after treatment start with Anakinra.
Description
Change in androstenedione level (nmol/l) from start (baseline, day 1) to days 14, 21, 28, and 35 after treatment start with Anakinra.
Time Frame
Days 14, 21, 28, and 35 after treatment start with Anakinra
Title
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
Description
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
Time Frame
Days 7, 14, 28, and 35 after treatment start with Anakinra

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mirjam Christ-Crain, Prof. Dr. MD
Organizational Affiliation
University Hospital Basel, Dep. of Endocrinology, Diabetes and Metabolism
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Basel Endocrinology, Diabetes and Metabolism
City
Basel
ZIP/Postal Code
4031
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No

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

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