Infertility, FemalePhase 1NCT03192527
Single Dose Recombinant Human Follicle Stimulating Hormone Fc Husion Protein (KN015) in Healthy Volunteers
A Phase 1 study testing KN015 and Triptorelin in people with Infertility, Female, run by Alphamab Jilin Co., Ltd. at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility, Female
- What is being tested?
- KN015 and Triptorelin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- Jun 2017to Jun 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
- Thyroid dysfunction which clinical significance by researchers of the study.
- Other abnormal laboratory tests with clinically relevance.
- Abnormal electrocardiogram [ECG] findings.
- III/IV class endometriosis, submucous myoma of uterus, endocrine abnormalities within 6 months prior to the study.
- Abnormal imaging examination and clinical significance judged by researchers of the study.
- Pregnancy or lactation period.
- Alcohol and urine drug screening positive. -
Trial locations and contacts
1 site in 1 country.
lei gao, M.D. contact
China1 site, 1 recruiting
- Recruiting
The First Hospital of Jilin University
Chuangchun, Jilin, 0431
Yanhua Ding, M.D., 86-0431-88782168, dingyanhua2003@126.com
About this study
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
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.
Read the 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.
- Conditions
- Infertility, Female
- Being tested
- KN015, Placebo, Triptorelin
- Keywords
- KN015, Long-acting FSH
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KN015Drug
experimental drug
PlaceboDrug
Comparator.
TriptorelinDrug
The drug is used for down-regulation of endogenous FSH.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | KN015, Triptorelin Receives: Drug: KN015; Drug: Triptorelin |
| Arm B | Placebo comparator | placebo, Triptorelin Receives: Drug: Placebo; Drug: Triptorelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment(SAEs) and AEs of special interest.
Measured: From screening to up to 36 days
Maximum observed serum concentration (Cmax) of KN015 in healthy Chinese female subjects
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: screening,-1,2,4,6,8,11,15,22,29,36 days post-dose
The size of follicles after dosing.
Measured: 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.
Measured: From screening to up to 36 days
Percentage of participants with anti-KN015 antibody.
Measured: -1,8,15,36 days post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2017
- Study startJun 2017 (estimated)
- Primary completionMar 2019 (estimated)
- Study completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infertility, FemaleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alphamab Jilin Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03192527
- Sponsor's protocol ID
- KNJR-2017-001
- Status last verified
- Jun 2017
- First submitted
- 14 Jun 2017
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36537742
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03192527
- Acronym / sponsor ID
- KNJR-2017-001
- Conditions
- Infertility, Female
- Keywords
- KN015, Long-acting FSH
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Alphamab Jilin Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Jun 2017 (estimated)
- Primary completion
- Mar 2019 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 20 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: KN015, Drug: TriptorelinKN015, Triptorelin |
| Arm B | Placebo comparator | Drug: Placebo, Drug: Triptorelinplacebo, Triptorelin |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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).
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KN015experimental drug | Drug | Arm A |
| PlaceboComparator. | Drug | Arm B |
| TriptorelinThe drug is used for down-regulation of endogenous FSH. | Drug | Arm A, Arm B |
Primary outcome
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
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.
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.
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.
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.
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.
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.
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.
4 secondary outcomes
The number of follicles after dosing.
Time frame: screening,-1,2,4,6,8,11,15,22,29,36 days post-dose
The size of follicles after dosing.
Time frame: 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.
Time frame: From screening to up to 36 days
Percentage of participants with anti-KN015 antibody.
Time frame: -1,8,15,36 days post-dose
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2017.
- Derived from this study: PubMed 36537742Zhang 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
lei gao, M.D. contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KN015 and Triptorelin in people with Infertility, Female, run by Alphamab Jilin Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yanhua Ding, M.D. (86-0431-88782168, dingyanhua2003@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03192527, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2017.