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HemophiliaPhase 2NCT05421429

KN057 Multiple Dose Study in Moderately Severe to Severe Hemophilia

A Phase 2 study testing KN057 doseⅠ, KN057 dose Ⅱ and KN057 dose Ⅲ in people with Hemophilia, run by Suzhou Alphamab Co., Ltd. at 2 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of multiple subcutaneous doses of KN057 in subjects with hemophilia A or B, with or without inhibitors to Factor VIII (FVIII) or Factor IX (FIX). Read more about this study

Who is it for?
Ages 18 to 70 years, men only
Conditions the study is for
Hemophilia
What is being tested?
KN057 doseⅠ, KN057 dose Ⅱ and KN057 dose Ⅲ
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
2 sitesChina
Study dates
7 Jul 2022to 17 Jan 2024
Phase
Phase 2
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 70 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male, 18-70 years old (including threshold), weight≥40kg;
  • Moderately severe to severe hemophilia A or B (Factor VIII or Factor IX activity ≤2%)
  • Participants who are enrolled into the Non-Inhibitor Cohort must meet the following criteria:
  • ①negtive results of of inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in screening period.
  • ②with ≥6 acute bleeding episodes (spontaneous or traumatic, not including episodes of bleeding during surgery) that required treatment within 6 months before screening and willing to continue to receive on-demand treatment during the study.
  • ③using coagulation factor replacement therapy for more than 50 exposure days before screening.
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  • Participants who are enrolled into the Inhibitor Cohort must meet the following criteria:
  • ①positive results of inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in screening period.
  • ②with ≥6 acute bleeding episodes (spontaneous or traumatic, not including episodes of bleeding during surgery) that required treatment within 6 months before screening and willing to continue to receive on-demand treatment during the study.
  • Be willing to undergo a washout period of the original treatment regimen before the administration of KN057: at least 48 hours for recombinant activated coagulation factor Ⅶ (rFⅦa); at least 72 hours for FⅧ and prothrombin complex (PCC); at least 96 hours for FⅨ; For other drugs or investigational products with a long half-life, such as Emicizumab, at least five half-lives should have passed prior to dosing.
  • Be willing to comply with the relevant management regulations of the clinical trial unit, and follow study procedures.

Who cannot join

  • Patients with serious or poorly controlled chronic diseases or obvious systemic diseases, such as cardiovascular system, respiratory system, endocrine and metabolic system, urinary system, digestive system, autoimmune diseases, nervous system diseases or psychiatric diseases, bacterial or viral infections, etc.; past or current lipid-lowering treatment for hypertriglyceridemia.
  • Inherited or acquired bleeding disorder other than hemophilia A or B.
  • Have symptoms or signs related to thromboembolic disease or are receiving thrombolytic/anti-thrombolytic therapy; A history of coronary atherosclerotic diseases, arterial or venous thrombosis, and ischemic diseases of important organs.
  • Conditions that may increase risk of thrombosis: including reduced activity of antithrombin III, protein S or protein C;
  • Must use PCC to treat acute bleeding episodes, and can't be treated with rFVIIa.
  • Ongoing or planned use of immune tolerance induction.
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  • Regular use of immunomodulatory therapy, such as regular infusion of immunoglobulin or regular use of hormones.
  • Allergy situation: Allergic to test drugs/similar drugs or excipients; With a history of multiple allergies (two or more); A history of specific reactions, such as sensitivity to heparin or heparin induced thrombocytopenia.
  • Abnormal hematologic parameters: Platelet count≤100×10^9/L; Hemoglobin < 100g/L; Fibrinogen level < LLN; Prothrombin time > 1.5 times ULN;
  • Abnormal renal or hepatic function: Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 3 times ULN; Lactate dehydrogenase (LDH) > 1.5 times ULN; Total bilirubin (TB) > 1.5 times ULN; Serum creatinine (Cr) and triglyceride > ULN; Albumin < 0.8 times LLN;
  • Chronic active hepatitis B/C (HBV-DNA or HCV-RNA quantitative test indicates viral activity); Human immunodeficiency virus (HIV) antibody positive; Syphilis antibody positive; Previous antiviral treatment within 1 month, or a plan for antiviral treatment within 28 weeks of initial administration.
  • Had major surgery, as judged by the investigator, within 3 months prior to the study or have elective surgery planned within 28 weeks of initial administration.
  • Need to use anti-fibrinolytic drugs or drugs affecting platelet function 5 days before administration or 28 weeks after initial administration, including Traditional Chinese medicine/proprietary Chinese medicine, such as aspirin and other non-steroidal anti-inflammatory drugs, Angelica, astragalus, etc., or proprietary Chinese medicine containing the above ingredients.
  • Participated in clinical trials related to coagulation factors within 1 month; Participated in any other drug clinical trials within 3 months.
  • Vaccination within 1 month, or within 28 weeks after initial administration, including inactivated vaccines, live attenuated vaccines, recombinant protein vaccines, recombinant adenovirus vaccines, RNA vaccines, DNA vaccines, etc.;
  • Subjects with fertile partners are not willing to use effective contraception during the study period and for 3 months after the last dosing; Effective contraceptive methods include: vasectomy, adhere to the scientific use of male condoms, etc.
  • Other factors that the investigator considers unacceptable for participation in the study.

Trial locations and contacts

2 sites in 1 country.

China2 sites

  • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

    Tianjin, Tianjin Municipality, 300020

  • stitute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

    Tianjin, Tianjin Municipality, 300020

Other trials in China

About this study

Official title: An Open, Multicenter, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Subcutaneous (SC) Doses of KN057 in Subjects with Hemophilia a or B, with or Without Inhibitors

This study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of multiple subcutaneous doses of KN057 in subjects with hemophilia A or B, with or without inhibitors to Factor VIII (FVIII) or Factor IX (FIX). 24 adult participants 18 to 70 years of age with moderately severe to severe hemophilia A or hemophilia B (defined as FVIII or FIX activity ≤2%, respectively) with or without inhibitors (including 18 HA/HB patients without inhibitors and 6 HA/HB patients with inhibitors) are expected to be enrolled in this study during which they will receive prophylaxis treatment (defined as treatment by SC injection once weekly of KN057).

Conditions
Hemophilia
Being tested
KN057 doseⅠ, KN057 dose Ⅱ, KN057 dose Ⅲ
Medical subject headings
Hemophilia A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KN057 doseⅠBiological

    KN057 subcutaneous (SC) injection

  • KN057 dose ⅡBiological

    KN057 SC injection

  • KN057 dose ⅢBiological

    KN057 SC injection

Study groups in NCT05421429
Study groupRoleWhat they receive
KN057 (Cohort 1：HA/HB)ExperimentalInjection, once a week
Receives: Biological: KN057 doseⅠ
KN057 (Cohort 2：HA/HB)ExperimentalInjection, once a week
Receives: Biological: KN057 dose Ⅱ
KN057 (Cohort 3：HA/HB)ExperimentalInjection, once a week
Receives: Biological: KN057 dose Ⅱ
KN057 (Cohort 4：HAW/HBW)ExperimentalInjection, once a week
Receives: Biological: KN057 dose Ⅲ

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency and severity of treatment emergent adverse events(TEAEs)

    An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) is any untoward medical occurrence at any dose that resulted in death; life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment.

    Measured: Day 1 up to Day 85

  2. Withdrawals due to TEAEs

    An AE is any untoward medical occurrence in a clinical investigation participant administered a product and the event does not need to have a causal relationship with the treatment. TEAEs are AEs occurred following the start of treatment or AEs increasing in severity during treatment.

    Measured: Day 1 up to Day 85

  3. Number of Participants With Abnormal Laboratory Findings-Hematology

    White blood cells, red blood cells; the count of lymphocyte, neutrophils, monocytes, eosinophils, basophils; the percentage of lymphocyte, neutrophils, monocytes, eosinophils, basophils; hemoglobin, red blood cell pressure, platelet count

    Measured: Day 1 up to Day 85

  4. Number of Participants With Abnormal Laboratory Findings-Urinalysis

    blood, urobilirubin, urobiliogen, ketone body, protein, nitrite, red blood cell (qualitative and/or quantitative), white blood cell (qualitative and/or quantitative), pH, urinary glucose.

    Measured: Day 1 up to Day 85

  5. Number of Participants With Abnormal Laboratory Findings-Blood biochemistry

    Total bilirubin and indirect bilirubin, direct bilirubin, alanine aminotransferase, aspertate aminotransferase, GGTP (gamma glutamyl transpeptidase), alkaline phosphatase, total protein, albumin, globulin, albumin-globulin ratio, urea, creatinine, uric acid, glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol (ldl-c), high-density lipoprotein cholesterol (hdl-c), lactate dehydrogenase, creatine kinase, chlorine, calcium, sodium, potassium, C reactive protein

    Measured: Day 1 up to Day 85

  6. Number of Participants With Abnormal Laboratory Findings-Coagulation tests

    Prothrombin time (PT), International Standardized ratio (INR), Activated partial thrombin time (APTT), thrombin time (TT), fibrinogen (FBG/FIB), D-dimer (D-DI), fibrinogen degradation product (FDP), antithrombin - ⅲ (AT- ⅲ)

    Measured: Day 1 up to Day 85

  7. Number of Participants With Clinically Significant Changes in Vital Signs Data

    Vital signs：blood pressure (systolic blood pressure, diastolic blood pressure), respiration, temperature, pulse；

    Measured: Day 1 up to Day 85

  8. Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)

    ECG: HR; RR; PR; QRS; QT; QTc

    Measured: Day 1 up to Day 85

  9. Number of Participants With Clinically Significant Changes in Physical Examination Findings

    Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Clinical significance was judged by the investigator.

    Measured: Day 1 up to Day 85

  10. Number of Participants With Injection Site Reactions

    Injection site reactions may include, but are not limited to: erythema, sclerosis, ecchymosis, pain, and itching.

    Measured: Day 1 up to Day 85

Secondary outcomes (14)

  1. Maximum Plasma Concentration (Cmax) of KN057

    Measured: Day 1 up to Day 8

  2. Time to Reach Maximum Plasma Concentration (Tmax) of KN057

    Measured: Day 1 up to Day 8

  3. Area Under the Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of KN057

    Measured: Day 1 up to Day 8

  4. Cmax,ss: Maximum observed KN057 concentration at steady-state

    Measured: Day 36 up to Day 43

  5. Time to Reach Maximum Plasma Concentration at steady-state (Tmax,ss) of KN057

    Measured: Day 36 up to Day 43

  6. Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of KN057

    Measured: Day 36 up to Day 43

  7. Apparent Clearance (CL/F) of KN057

    Measured: Day 36 up to Day 43

  8. Lowest Concentration Observed During the Dosing Interval (Cmin) of KN057

    Measured: Day 36 up to Day 43

  9. Pharmacodynamics index: Changes of TFPI from baseline;

    Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. TFPI: Total TFPI, Free TFPI

    Measured: Day 1 up to Day 169

  10. Pharmacodynamics index: Changes of Prothrombin fragment 1+2 (PF1+2) from baseline;

    Prothrombin fragment 1+2 (F1+2) is the amino terminus fragment of the prothrombin molecule.

    Measured: Day 1 up to Day 169

  11. Pharmacodynamics index: Thrombin Generation (TGA);

    Lag Time; Peak Thrombin; Endogenous Thrombin Potential;

    Measured: Day 1 up to Day 169

  12. Number of Participants Who Tested Positive for Anti-KN057 Antibody (ADA)

    Human plasma ADA samples were analyzed for the detection of anti KN057 antibodies.

    Measured: Day 1 up to Day 169

  13. Number of Participants Who Tested Positive for Neutralizing Antibody (NAb)

    Human plasma NAb samples were analyzed for the presence or absence of NAb to KN057.

    Measured: Day 1 up to Day 169

  14. Annualized Bleeding Rate

    ABR = number of bleeds requiring treatments/ (days on treatment period / 365.25)

    Measured: Day 1 up to Day 169

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2022
  2. Study start7 Jul 2022
  3. Primary completion17 Jan 2024
  4. Study completion17 Jan 2024

Resources

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 2
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05421429
Sponsor's protocol ID
KN057-A-201
Status last verified
Sep 2024
First submitted
9 Jun 2022
Last updated
30 Dec 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing KN057 doseⅠ, KN057 dose Ⅱ and KN057 dose Ⅲ in people with Hemophilia, run by Suzhou Alphamab Co., Ltd. at 2 sites 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 11 inclusion and 17 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: finished, as of the sponsor's last update on 30 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency and severity of treatment emergent adverse events(TEAEs) (time frame: Day 1 up to Day 85). The study lists 10 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 NCT05421429.

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 30 Dec 2024.

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