Single Dose Recombinant Human Follicle Stimulating Hormone Fc Husion Protein (KN015) in Healthy Volunteers

NCT03192527 | Unknown Phase 1 DMC

• 1 other identifier: KNJR-2017-001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

KN015,the active substance recombinant human Follicle Stimulating Hormone（FSH） Fc fusion protein, which belongs to the pharmaceutical class gonadotropins.KN015 is proposed for Assisted Reproductive Technology (ART) programs only. Its indication is Controlled Ovarian Stimulation （COS）in combination with a gonadotropin releasing hormone (GnRH) antagonist for the development of multiple follicles in women participating in an ART program. Due to its prolonged duration of FSH activity compared to conventional recombinant FSH (rFSH), a single subcutaneous injection of the recommended dose of KN015 may replace any daily rFSH preparation in a COS treatment cycle. This study is to evaluation of the safety, tolerability, pharmacokinetics and pharmacodynamics of KN015 in healthy Chinese female subjects.

Conditions

Infertility, Female

Keywords

KN015; Long-acting FSH

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment(SAEs) and AEs of special interest.

  From screening to up to 36 days

• Maximum observed serum concentration (Cmax) of KN015 in healthy Chinese female subjects

  within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.

• Time of Maximum observed serum concentration (Tmax) of KN015 in healthy Chinese female subjects.

  within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.

• Adjusted geometric means of area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUC(0-T)) for KN015.

  within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.

• Adjusted geometric means of area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) for KN015.

  within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.

• Serum Half-life (T-HALF) of KN015 in healthy Chinese female subjects.

  within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.

• Serum clearance (CL) of KN015 in healthy Chinese female subjects.

  within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.

• Volume of distribution at steady state (VSS) of KN015 in healthy Chinese female subjects.

  within 0.5 hour pre-dose, 2,5,8,12,24,30,36,40,48,54,60,72,96h,120,144,168,240,288,336,504,672 hours post-dose.

Secondary Outcomes (4)

• The number of follicles after dosing.

  screening,-1,2,4,6,8,11,15,22,29,36 days post-dose

• The size of follicles after dosing.

  screening,-1,2,4,6,8,11,15,22,29,36 days post-dose

• Determination of serum concentrations of FSH, E2, LH and P after dosing.

  From screening to up to 36 days

• Percentage of participants with anti-KN015 antibody.

  -1,8,15,36 days post-dose

Study Arms (2)

Arm A

EXPERIMENTAL

KN015, Triptorelin

Drug: KN015; Drug: Triptorelin

Arm B

PLACEBO COMPARATOR

placebo, Triptorelin

Drug: Placebo; Drug: Triptorelin

Interventions

KN015 DRUG

experimental drug

Arm A

Placebo DRUG

Comparator.

Arm B

Triptorelin DRUG

The drug is used for down-regulation of endogenous FSH.

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able and willing to provide written informed consent.
• Agreed to take effective contraceptive measures during and 6 months after the end of the study period.
• Age between 18 to 40 years (inclusive).
• Body weight ≥45 kg, body mass index (BMI) of ≥18 and ≤28 kg/m2,
• Regular menstruation cycle (25 to 34 days, inclusive).
• Healthy female volunteer, normal findings in medical history and physical examinations.
• Normal findings in sex hormone examinations unless the investigator considers an abnormality to be clinically irrelevant for this study.
• Negative for human immunodeficiency virus (HIV) I and II tests, hepatitis B surface antigen (HBsAg), hepatitis C antibody and schaudinn's bacillus antibody at screening.
• Normal uterus, presence of both ovaries, unless investigator considers an abnormality to be clinically irrelevant for this study.

You may not qualify if:

• Historic abuse of alcoholic beverages and drugs. Smoke ≥5 cigarettes or the equivalent per day. Drug screen will include the minimum the following: amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, methadone, opiates.
• History of hypersensitivity to FSH, or any documented or suspected allergy to KN015 or the excipients of the KN015 formulation, or hypersensitivity to luteinizing hormone releasing hormone agonist or something like that.
• Any medical history of circulation, endocrine, nervous, digestive and respiratory systems, hematology, immunology, psychiatry and metabolic disorders and other serious disease history which can interfere with the test results of the study.
• Polycystic ovary syndrome (PCOS).
• Baseline of serum FSH ≥15 IU/L.
• History of ovarian hyperstimulation syndrome (OHSS).
• Experience in controlled ovarian stimulation (COS), or showed high response to FSH stimulation or the number of follicles over 11mm in diameter is more than 30.
• The history of ovarian, breast, uterus, hypothalamus, and pituitary disease was determined by the investigators as clinical meaningful. Previous history of thrombosis or tending to suffer from thrombotic disease.
• History of malignant disease.
• Failing to comply with the special requirements of diet during study.
• Participation in a clinical study within 3 months prior to the study.
• Any medical condition that, in the opinion of the investigator, would interfere with safety of the subject or with the objectives of the study.
• Abnormal physical examinational results which is determined as clinical significance by the researchers of the study.
• Abnormal vital signs and clinical significance.
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>1.5 x ULN.

Sponsors & Collaborators

• Alphamab Jilin Co., Ltd.: lead

Study Sites (1)

The First Hospital of Jilin University

Chuangchun, Jilin, 0431, China

RECRUITING

Related Publications (1)

• Zhang H, Fan Y, Gao L, Wang B, Xu T, Wu M, Liu J, Zhu X, Li X, Chen H, Li C, Wang M, Liu C, Mao Y, Yang M, Ding Y. 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. Expert Opin Investig Drugs. 2022 Nov;31(11):1255-1263. doi: 10.1080/13543784.2022.2151434. Epub 2022 Dec 20.

  PMID: 36537742 DERIVED

MeSH Terms

Conditions

Infertility, Female

Interventions

Triptorelin Pamoate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Central Study Contacts

Yanhua Ding, M.D.

CONTACT

86-0431-88782168; dingyanhua2003@126.com

lei gao, M.D.

CONTACT

398027192@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: June 20, 2017
• Study Start: June 1, 2017
• Primary Completion: March 1, 2019
• Study Completion: June 1, 2019
• Last Updated: June 20, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)