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

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ClinicalTrials.gov Identifier: NCT03192527
Recruitment Status : Recruiting
First Posted : June 20, 2017
Last Update Posted : June 20, 2017
Sponsor:
Information provided by (Responsible Party):
Alphamab Jilin Co., Ltd.

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.

Condition or disease Intervention/treatment Phase
Infertility, Female Drug: KN015 Drug: Placebo Drug: Triptorelin Phase 1

Detailed Description:
This is a phase I, randomized, placebo-controlled, single ascending dose, double blind parallel design, first-in-human study. The study design allows a gradual escalation of the dose-level with intensive safety monitoring to ensure the safety of the subjects. Dose escalation will continue until identification of MTD or up to a maximum dose of 100 μg. Tolerability, safety, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity characteristics of KN015 will be assessed in healthy female subjects. Eligible subjects will undergo down-regulation of endogenous FSH with a GnRH antagonist Triptorelin prior to receiving KN015.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase I, Randomized, Placebo Controlled, Single Ascending Dose (SAD) Study of Recombinant Human Follicle Stimulating Hormone Fc Fusion Protein (KN015) in Healthy Female Volunteers
Estimated Study Start Date : June 2017
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Triptorelin

Arm Intervention/treatment
Experimental: Arm A
KN015, Triptorelin
Drug: KN015
experimental drug

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

Placebo Comparator: Arm B
placebo, Triptorelin
Drug: Placebo
Comparator.

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




Primary Outcome Measures :
  1. Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment(SAEs) and AEs of special interest. [ Time Frame: From screening to up to 36 days ]
  2. Maximum observed serum concentration (Cmax) of KN015 in healthy Chinese female subjects [ Time Frame: 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. ]
  3. Time of Maximum observed serum concentration (Tmax) of KN015 in healthy Chinese female subjects. [ Time Frame: 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. ]
  4. 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. [ Time Frame: 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. ]
  5. Adjusted geometric means of area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) for KN015. [ Time Frame: 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. ]
  6. Serum Half-life (T-HALF) of KN015 in healthy Chinese female subjects. [ Time Frame: 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. ]
  7. Serum clearance (CL) of KN015 in healthy Chinese female subjects. [ Time Frame: 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. ]
  8. Volume of distribution at steady state (VSS) of KN015 in healthy Chinese female subjects. [ Time Frame: 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 Outcome Measures :
  1. The number of follicles after dosing. [ Time Frame: screening,-1,2,4,6,8,11,15,22,29,36 days post-dose ]
  2. The size of follicles after dosing. [ Time Frame: screening,-1,2,4,6,8,11,15,22,29,36 days post-dose ]
  3. Determination of serum concentrations of FSH, E2, LH and P after dosing. [ Time Frame: From screening to up to 36 days ]
  4. Percentage of participants with anti-KN015 antibody. [ Time Frame: -1,8,15,36 days post-dose ]


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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Able and willing to provide written informed consent.
  2. Agreed to take effective contraceptive measures during and 6 months after the end of the study period.
  3. Age between 18 to 40 years (inclusive).
  4. Body weight ≥45 kg, body mass index (BMI) of ≥18 and ≤28 kg/m2,
  5. Regular menstruation cycle (25 to 34 days, inclusive).
  6. Healthy female volunteer, normal findings in medical history and physical examinations.
  7. Normal findings in sex hormone examinations unless the investigator considers an abnormality to be clinically irrelevant for this study.
  8. 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.
  9. Normal uterus, presence of both ovaries, unless investigator considers an abnormality to be clinically irrelevant for this study.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. Polycystic ovary syndrome (PCOS).
  5. Baseline of serum FSH ≥15 IU/L.
  6. History of ovarian hyperstimulation syndrome (OHSS).
  7. 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.
  8. 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.
  9. History of malignant disease.
  10. Failing to comply with the special requirements of diet during study.
  11. Participation in a clinical study within 3 months prior to the study.
  12. Any medical condition that, in the opinion of the investigator, would interfere with safety of the subject or with the objectives of the study.
  13. Abnormal physical examinational results which is determined as clinical significance by the researchers of the study.
  14. Abnormal vital signs and clinical significance.
  15. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >1.5 x ULN.
  16. Thyroid dysfunction which clinical significance by researchers of the study.
  17. Other abnormal laboratory tests with clinically relevance.
  18. Abnormal electrocardiogram [ECG] findings.
  19. III/IV class endometriosis, submucous myoma of uterus, endocrine abnormalities within 6 months prior to the study.
  20. Abnormal imaging examination and clinical significance judged by researchers of the study.
  21. Pregnancy or lactation period.
  22. Alcohol and urine drug screening positive. -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03192527


Contacts
Contact: Yanhua Ding, M.D. 86-0431-88782168 dingyanhua2003@126.com
Contact: lei gao, M.D. 398027192@qq.com

Locations
China, Jilin
The First Hospital of Jilin University Recruiting
Chuangchun, Jilin, China, 0431
Contact: Yanhua Ding, M.D.    86-0431-88782168    dingyanhua2003@126.com   
Sponsors and Collaborators
Alphamab Jilin Co., Ltd.

Responsible Party: Alphamab Jilin Co., Ltd.
ClinicalTrials.gov Identifier: NCT03192527     History of Changes
Other Study ID Numbers: KNJR-2017-001
First Posted: June 20, 2017    Key Record Dates
Last Update Posted: June 20, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alphamab Jilin Co., Ltd.:
KN015
Long-acting FSH

Additional relevant MeSH terms:
Infertility, Female
Infertility
Genital Diseases, Male
Genital Diseases, Female
Hormones
Follicle Stimulating Hormone
Triptorelin Pamoate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Luteolytic Agents
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents