Healthy Female Adult Volunteers
Conditions
Brief summary
A study to investigate the pharmacokinetics and safety of KM04 compared to United States (US)-Gonal-f Revised Formulation Female (RFF) Redi-ject and European Union (EU)-Gonal-f in healthy adult female volunteers
Detailed description
A Single Center, Single-Dose, Double-Blind, Randomized, Three-Treatment, Three-Period, Six-Sequence, Crossover Study to Demonstrate Pharmacokinetic Similarity Between KM04, US-Gonal-f® RFF Redi-ject®, EU-Gonal-f®, and to Evaluate Safety in Healthy Adult Female Volunteers
Interventions
DRUGKM04
Participants will receive a single subcutaneous dose of 300 International Unit (IU) in either Treatment Period 1, Treatment Period 2, or Treatment Period 3.
DRUGUnites States (US)-Gonal-f® Revised Formulation Female (RFF) Redi-ject®
Participants will receive a single subcutaneous dose of 300 IU in either Treatment Period 1, Treatment Period 2, or Treatment Period 3.
DRUGEuropean Union (EU)-Gonal-f®
Participants will receive a single subcutaneous dose of 300 IU in either Treatment Period 1, Treatment Period 2, or Treatment Period 3.
Sponsors
Xentria, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participant must be 18 to 40 years of age inclusive, at the time of signing the informed consent. 2. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and 12-lead electrocardiogram (ECG) at screening. 3. Body weight ≥ 45 kg and body mass index (BMI) within the range 18.0-30.0 kg/m2 (inclusive). 4. Female assigned at birth, inclusive of all gender identities. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies (See Section 10.3.1). 5. Administration of combined oral contraceptives for at least 2 consecutive menstrual periods before downregulation and continued until 4 weeks following the last administration of study intervention. 6. Presence of both ovaries. 7. History of regular menstrual cycle (24 to 35 days) prior to the initiation of oral contraceptives. 8. Signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion criteria
1. Participant is pregnant, breastfeeding, or plans to become pregnant or breastfeed during the course of the study. 2. Sensitivity to any of the study interventions, follicle-stimulating hormone (FSH), lutenizing hormone, or components thereof, or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study. 3. History or presence of cardiovascular, respiratory, psychiatric, metabolic, hepatic, renal, gastrointestinal, endocrinological, hematological, oncological, or neurological disorders. 4. History of previous deep vein thrombosis (DVT), pulmonary embolism or any other thromboembolic or similar events. 5. History or presence of polycystic ovary syndrome or uterine fibroids. 6. History or presence of impaired thyroid function. 7. Evidence of active infection, including chronic or localized infections, by history, physical examination findings, or laboratory data, as determined by the Investigator within 1 week prior to Day 1 of Treatment Period 1. 8. Rash, scarring, dermatological condition, or tattoo in the area of the injection site that could interfere with the injection or injection site assessment. 9. History or presence of any condition that in the opinion of the investigator would constitute a risk when taking the study intervention or interfere with the interpretation of data. 10. History or presence of drug or alcohol abuse per Investigator's discretion 11. History or regular use of tobacco- or nicotine-containing products within 3 months prior to screening. 12. Past or intended use of prescription medication or over-the-counter medication including herbal medications within 4 weeks or 5 half-lives (whichever is longer) prior to dosing. 13. Concurrent enrollment or past participation in another investigational study in which an investigational intervention (e.g., drug, vaccine, invasive device) was administered within 90 days or 5 half-lives (whichever is longer) before planned first dose of study intervention in this clinical study. 14. FSH level \> 5 IU/ml at Day -23 of Treatment Period 1. 15. Estradiol level \> 90 pg/mL at Day -23 of Treatment Period 1. 16. Presence of ovarian cysts \> 3 cm in diameter at screening or Day -23 of Treatment Period 1, or any other cyst at the Investigator's discretion. 17. Presence of \> 40 follicles at screening or Day -23 of Treatment Period 1. 18. Positive drug/alcohol screen at screening or Day -1. 19. Presence of hepatitis B surface antigen, positive human immunodeficiency virus (HIV), or positive hepatitis C antibody test at screening. 20. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>2 x upper limit of normal reference range at screening. 21. Other clinically relevant findings at screening. 22. Unwilling to abstain from alcohol or other prohibited drugs or medications for 48 hours prior to dosing through the duration of each Clinical Research Unit (CRU) visit. 23. Participants will be screened for FSH anti-drug antibodies at prescreening, and subjects found positive above cut-off levels (to be determined during validation) will be excluded from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed serum concentration (Cmax) | 0 to 192 hours | To compare the Pharmacokinetic (PK) similarity in healthy female participants between KM04, Unites States (US)-Gonal-f revised formulation female (RFF) Redi-ject and European Union (EU)-Gonal-f |
| Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t) | 0 to 192 hours | To compare the Pharmacokinetic (PK) similarity in healthy female participants between KM04, Unites States (US)-Gonal-f revised formulation female (RFF) Redi-ject and European Union (EU)-Gonal-f |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) | 0 to 192 hours | To evaluate additional PK parameters of KM04, US-Gonal-f RFF Redi-ject, and EU-Gonal-f |
| Time to Cmax (Tmax) | 0 to 192 hours | To evaluate additional PK parameters of KM04, US-Gonal-f RFF Redi-ject, and EU-Gonal-f |
| Terminal half-life (t1/2) | 0 to 192 hours | To evaluate additional PK parameters of KM04, US-Gonal-f RFF Redi-ject, and EU-Gonal-f |
| The proportion of participants with a negative baseline anti-drug antibody (ADA) test result and confirmed post dose positive ADA test result at any time during the study | Baseline to the End-of-Study (EOS) visit, approximately 12 weeks | To compare the immune response of KM04, US-Gonal-f RFF Redi-ject, and EU-Gonal-f for the assessment of immunogenicity |
| The proportion of participants with a negative baseline ADA test result and confirmed post dose positive neutralizing antibody (NAb) result at any time during the study | Baseline to the End-of-Study (EOS) visit, approximately 12 weeks | To compare the immune response of KM04, US-Gonal-f RFF Redi-ject, and EU-Gonal-f for the assessment of immunogenicity |
| Adverse event (AE) assessments | Baseline to the End-of-Study (EOS) visit, approximately 12 weeks | To assess the safety and tolerability of KM04, US-Gonal-f RFF Redi-ject, and EU-Gonal-f |
Outcome results
None listed