The effect of a single escalating dose of long-acting recombinant human follicle-stimulating hormone Fc fusion protein (KN015) on healthy, pituitary-suppressed women: first-in-human and randomized study on its pharmacokinetics, pharmacodynamics, and tolerability

ABSTRACT

Objective

KN015 is a long-acting, recombinant human follicle-stimulating hormone Fc fusion protein that induces follicle development. This first-in-human study evaluated the effect of KN015 on healthy, pituitary-suppressed women and examined its pharmacokinetics, pharmacodynamics, and tolerability.

Methods

This phase I study was a double-blind, randomized, and placebo-controlled design with a single ascending dose (20, 40, and 60 μg, respectively).

Results

After subcutaneous administration of a single dose, the maximum serum KN015 concentrations reached 1.57, 2.78, and 3.62 ng/mL, respectively, after baseline adjustment. Over this dose range, the median T_max occurred at 240–312 h, and the half-life (t_½) was 752–1160 h. Dose proportionality was shown across the studied dose range. In most subjects, follicular growth was observed, and the number and diameter of the follicles increased with an increasing dose. In the 40-μg and 60-μg groups, the mean numbers of follicles with a diameter of ≥17 mm were 3 and 4, respectively. There was no significant difference in adverse events between the KN015 and placebo groups. KN015 antibody was not detected in any of the dosage groups.

Conclusion

The administration of a single ascending dose of KN015 was tolerated and able to induce follicular growth.

Trial registration

This trial is registered at the Chinese Clinical Trials website (http://www.chinadrugtrials.org.cn/index.html # CTR20160741) and ClinicalTrials.gov (https://clinicaltrials.gov/ # NCT03192527).

KEYWORDS:

• KN015
• assisted reproduction technology
• long-acting FSH
• pharmacodynamics
• pharmacokinetics

Acknowledgments

The authors thank the staff and subjects who participated in this study.

Author contributions

H Zhang and Y Ding were responsible for the acquisition, analysis, or interpretation of data. HZ was responsible for the statistical analysis. All authors contributed to the study concept, design, and supervision; interpretation of the data; and preparation of the manuscript. All authors approved the final version. All authors verified the underlying data.

Declaration of interest

All data related to this study were interpreted by the trial staff with complete independence from the sponsor. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Data availability statement

The data that support the findings of this study are available from the corresponding author, Y Ding, upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13543784.2022.2151434.

Additional information

Funding

This work was financially supported by the Capital Construction Funds within the provincial budget in 2020 (in the category of Innovation Capacity Construction, project number: 2020C038-1), and was also sponsored by Corning Jeri (Jilin) Biotechnology Co., Ltd.