SS109 and NovoSeven ® PK / PD Profile, and Preliminary Efficacy and Safety of SS109 on Demand Treatment

• ClinicalTrials.gov Identifier: NCT06010953
• Recruitment Status: Recruiting
• First Posted: August 25, 2023
• Last Update Posted: February 29, 2024
• Sponsor: Jiangsu Gensciences lnc.
• Information provided by (Responsible Party): Jiangsu Gensciences lnc.

Tracking Information

• First Submitted Date: August 15, 2023
• First Posted Date: August 25, 2023
• Last Update Posted Date: February 29, 2024
• Actual Study Start Date: October 12, 2023
• Estimated Primary Completion Date: May 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 24, 2023)

• Cmax [ Time Frame: Day 1 to Day 6 ]
  According to the detected FVII activity of SS109 and NovoSeven®, the peak activity (Cmax)
• Four-level rating scale to assess hemostasis [ Time Frame: Day 7 to Day 96 ]
  Hemostasis 12 h after on-demand treatment. For each new blood event, on-demand treatment should be conducted within 15min before each administration after the first dose The hemostatic effect of pain and bleeding symptoms/signs observed and recorded after the last treatment was evaluated according to a four-level scoring scale. If clinically effective (rated as "excellent" or "good") is achieved, the evaluation is discontinued.
• Tmax [ Time Frame: Day 1 to Day 6 ]
  According to the detected FVII activity of SS109 and NovoSeven®,time to peak concentration (Tmax),
• AUC0-t [ Time Frame: Day 1 to Day 6 ]
  area under the concentration-time curve from time 0 to the last quantifiable time point (AUC0-t) will be calculated

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 24, 2023)

• Efficacy of hemostasis before each dose (except first dose) after treatment of all bleeding events [ Time Frame: Day 7 to Day 96 ]
  On-demand treatment Percentage rated "good" or "very good" before each dose after the first dose of on-demand treatmen
• Time to "good" or "excellent" evaluation after treatment for all hemorrhage events [ Time Frame: Day 7 to Day 96 ]
  Time to "good" or "excellent" evaluation after treatment for all hemorrhage events
• Evaluate the incidence of AE/SAE/AESI [ Time Frame: Day 1 to Day 96 ]
  Safety Measures
• Incidence of positivity for FVII inhibitors [ Time Frame: Day 1 to Day 96 ]
  Immunogenicity Measure
• anti-drug antibodies (ADAs) [ Time Frame: Day 1 to Day 96 ]
  Immunogenicity Measures
• CHO host cell antibodies [ Time Frame: Day 1 to Day 96 ]
  Immunogenicity Measure

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 24, 2023)

• AUC0-inf [ Time Frame: Day 1 to Day 6 ]
  If data allows, the area under the concentration-time curve from time 0 to infinity (AUC0-inf)
• (λz [ Time Frame: Day 1 to Day 6 ]
  clearance (CL), elimination rate constant (λz)
• t1/2 [ Time Frame: Day 1 to Day 6 ]
  elimination half-life
• Vd [ Time Frame: Day 1 to Day 6 ]
  volume of distribution (Vd)
• AUC_%Extrap [ Time Frame: Day 1 to Day 6 ]
  extrapolated percentage of area under the concentration-time curve (%) (AUC_%Extrap)
• MRT [ Time Frame: Day 1 to Day 6 ]
  mean residence time

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: SS109 and NovoSeven ® PK / PD Profile, and Preliminary Efficacy and Safety of SS109 on Demand Treatment
• Official Title: An Open-label and Multicenter Phase Ib/II Clinical Trial to Evaluate the Safety, Immunogenicity, PK/PD Profile of SS109 and NovoSeven® Following a Single Dose, and the Preliminary Efficacy and Safety of SS109 During On-demand Treatment in Hemophilia Patients With Coagulation Factor VIII or IX Inhibitors

Brief Summary

This is an open-label, multicenter Phase 1Ib/2II clinical trial of SS109 in adult hemophilia patients (≥ 18 years) with FVIII or FIX inhibitors to evaluate the PK/PD profile of SS109 and NovoSeven® after a single dose in adult hemophilia patients with FVIII or FIX inhibitors, to assess the preliminary efficacy and PK profile of SS109 during on-demand treatment, and to observe the safety and immunogenicity of SS109 throughout the study.

The trial consists of three periods: screening period, PK study period, and on-demand treatment period.

In the PK study period, subjects are divided into 2 cohorts (90 μg/kg and 270 μg/kg), which are sequentially conducted. Cohort 1 (90 μg/kg) enrollment is performed firstly, and Cohort 2 (270 μg/kg) enrollment is performed after Cohort 1 enrollment is completed. Subjects enter the PK study period as non-randomized. All screened eligible subjects will receive a single dose of comparator NovoSeven® in the absence of significant active hemorrhage, followed by PK/PD sample collection; then receive a single dose of the same dose of investigational drug SS109, followed by PK/PD sample collection. Specific times for PK/PD sample collection are listed in the schedule for biological sample collection.

After completion of the PK study period, subjects will enter a 90-day on-demand treatment period and will be randomized into 3 groups (Group 1: 90 µg/kg, Group 2: 180 µg/kg, and Group 3: 270 µg/kg) at a ratio of 1:1:1. During on-demand treatment, subjects are treated on-demand with SS109 at the time of a new hemorrhage event and their efficacy is observed. The investigator will judge the severity of subject's hemorrhage according to the type, location, clinical symptoms and signs of the subject's hemorrhage. Appropriate hemostatic treatment regimens and whether or not to perform the first SS109 on-demand treatment for the hemorrhage event at home may be developed by the investigator based on the subject's on-demand treatment group, according to the severity of hemorrhage and the recommended dosing frequency of SS109 (see Dosage/Regimen), and the dosing interval may be adjusted in conjunction with the subject's response to treatment. If the subject's last hemostatic treatment is administered within one week before the D96 visit point during the on-demand treatment period, the subject is required to continue follow-up observation for one week after the last dose before completing the end of study visit. PK/PD samples will be collected as appropriate during on-demand treatment, as specified in the schedule for biological sample collection.Observe subject safety throughout the study.

Detailed Description

This is an open-label, multicenter Phase 1Ib/2II clinical trial of SS109 in adult hemophilia patients (≥ 18 years) with FVIII or FIX inhibitors to evaluate the PK/PD profile of SS109 and NovoSeven® after a single dose in adult hemophilia patients with FVIII or FIX inhibitors, to assess the preliminary efficacy and PK profile of SS109 during on-demand treatment, and to observe the safety and immunogenicity of SS109 throughout the study.

The trial consists of three periods: screening period, PK study period, and on-demand treatment period.

In the PK study period, subjects are divided into 2 cohorts (90 μg/kg and 270 μg/kg), which are sequentially conducted. Cohort 1 (90 μg/kg) enrollment is performed firstly, and Cohort 2 (270 μg/kg) enrollment is performed after Cohort 1 enrollment is completed. Subjects enter the PK study period as non-randomized. All screened eligible subjects will receive a single dose of comparator NovoSeven® in the absence of significant active hemorrhage, followed by PK/PD sample collection; then receive a single dose of the same dose of investigational drug SS109, followed by PK/PD sample collection. Specific times for PK/PD sample collection are listed in the schedule for biological sample collection.

After completion of the PK study period, subjects will enter a 90-day on-demand treatment period and will be randomized into 3 groups (Group 1: 90 µg/kg, Group 2: 180 µg/kg, and Group 3: 270 µg/kg) at a ratio of 1:1:1. During on-demand treatment, subjects are treated on-demand with SS109 at the time of a new hemorrhage event and their efficacy is observed. The investigator will judge the severity of subject's hemorrhage according to the type, location, clinical symptoms and signs of the subject's hemorrhage. Appropriate hemostatic treatment regimens and whether or not to perform the first SS109 on-demand treatment for the hemorrhage event at home may be developed by the investigator based on the subject's on-demand treatment group, according to the severity of hemorrhage and the recommended dosing frequency of SS109 (see Dosage/Regimen), and the dosing interval may be adjusted in conjunction with the subject's response to treatment. If the subject's last hemostatic treatment is administered within one week before the D96 visit point during the on-demand treatment period, the subject is required to continue follow-up observation for one week after the last dose before completing the end of study visit. PK/PD samples will be collected as appropriate during on-demand treatment, as specified in the schedule for biological sample collection.

Observe subject safety throughout the study.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Male
• Hemophilia A With Inhibitor
• Hemophilia B With Inhibitor
• Hemophilia

Intervention

Drug: SS109

on-demand treatment with SS109 at the time of a new hemorrhage event

Study Arms

• Experimental: PK period: Cohort 1 (90 μg/kg) and Cohort 2 (270 μg/kg)
  In the PK study period, subjects are divided into 2 cohorts (90 μg/kg and 270 μg/kg), which are sequentially conducted. Cohort 1 (90 μg/kg) enrollment is performed firstly, and Cohort 2 (270 μg/kg) enrollment is performed after Cohort 1 enrollment is completed. Subjects enter the PK study period as non-randomized. All screened eligible subjects will receive a single dose of comparator NovoSeven® in the absence of significant active hemorrhage, followed by PK/PD sample collection; then receive a single dose of the same dose of investigational drug SS109, followed by PK/PD sample collection.
  Intervention: Drug: SS109
• Experimental: On-demand treatment period: Group 1：90 μg/kg Group 2：180 μg/kg Group 3：270 μg/kg
  After completion of the PK study period, subjects will enter a 90-day on-demand treatment period and will be randomized into 3 groups (Group 1: 90 µg/kg, Group 2: 180 µg/kg, and Group 3: 270 µg/kg) at a ratio of 1:1:1. During on-demand treatment, subjects are treated on-demand with SS109 at the time of a new hemorrhage event and their efficacy is observed.
  Intervention: Drug: SS109

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 24, 2023): 24
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 31, 2024
• Estimated Primary Completion Date: May 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Aged 18 to 65 years at the time of informed consent, male;

2. Patients with clinical diagnosis of hemophilia A or B (FVIII activity level ≤ 1% or FIX activity level ≤ 2% in the previous or screening period) who meet one of the following conditions:

   FVIII or FIX inhibitor level ≥ 5 Bu/mL at screening; FVIII or FIX inhibitor level < 5 Bu/mL and ≥ 0.6 Bu/mL at screening, with a high response to coagulation factor VIII or IX for injection (i.e., the patient has a previous history of positive FVIII/FIX inhibitor and inhibitor levels are ≥ 5 Bu/mL after reinfusion of FVIII/FIX).

3. No active bleeding symptoms prior to the first dose;
4. Subjects or impartial witnesses fully understand and comply with the requirements of the study protocol and are willing to complete the study as planned, and voluntarily cooperate in providing biological samples for testing as required by the protocol;
5. Be able to understand the procedures and methods of this clinical trial, and after fully informed consent, the patient voluntarily participates and signs the informed consent form by the patient himself or an impartial witness.

Exclusion Criteria:

1. Patients with a known history of hypersensitivity to the investigational product or any of its components;
2. Patients with previous hypersensitivity or anaphylaxis after FVII or IgG2 injection therapy;
3. Patients with positive FVII inhibitors or history of positive FVII inhibitors at screening;
4. Patients with severe anemia (hemoglobin < 60 g/L);
5. Patients with platelet count < 100 × 109/L;

6. Patients with abnormal liver and kidney function:

   • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times the upper limit of normal (ULN); or
   • Serum total bilirubin (TBIL) ≥ 1.5 times ULN; or
   • Serum creatinine (Cr) ≥ 1.5 times ULN or creatinine clearance < 60 mL/min calculated according to the Cockcroft-Gault formula;
7. Patients with one or more positive tests for hepatitis B virus surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibody, anti-human immunodeficiency virus (HIV) antibody, and anti-treponema pallidum hemagglutination (TPHA)-specific antibody;
8. With the exception of hemophilia A or B, any other haemorrhagic disorders or significantly abnormal coagulation indicators (such as platelet disease, vitamin K deficiency and hypofibrinogenaemia) caused by other diseases;
9. Patients with fever, active infection and allergy (such as allergic rhinitis, allergic asthma, allergic dermatitis) within 2 weeks before the first dose;
10. Patients with severe cardiovascular and cerebrovascular diseases or thromboembolic diseases occurred within 6 months before the first dose, such as cerebral arteritis, moyamoya disease, cerebral stroke, viral myocarditis, endocarditis, endocardial fibroelastosis, severe arrhythmia, myocardial infarction, unstable angina pectoris, congestive heart failure (New York Heart Association Grade ≥ III), uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) and uncontrolled diabetes;
11. Patients receiving or planning to receive immune tolerance induction (ITI) treatment during the trial;
12. Receipt of any product containing FVII or FVIIa (plasma source or recombinant) within 24 hours before the first dose;
13. Receipt of any product containing FVIII (plasma source or recombinant) within 72 hours or 5 half-lives (whichever is longer) before the first dose or any product containing FIX (plasma source or recombinant) within 96 hours or 5 half-lives (whichever is longer) before the first dose;
14. Patients who have used any anticoagulants, antifibrinolytic agents, and chemical drugs, biological products or traditional Chinese medicines affecting platelet function within 1 week before the first dose, including non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin;
15. Patients who have received emicizumab within 6 months before the first dose;
16. Patients who have received immunomodulators (such as gamma globulin, interferon-alpha and prednisone > 10 mg/d [and > 7 days] or similar drugs, except antiretroviral drugs) within 2 weeks before the first dose;
17. Patients who have received whole blood or plasma therapy within 2 weeks before the first dose;
18. Received vaccination within 4 weeks before the first dose or planned vaccination during the PK study;
19. Patients who underwent major surgical operations (e.g. orthopedic surgery, abdominal surgery) within 1 month before the first dose, or plan to undergo surgery during the study period;
20. Patients who enrolled in other clinical trials within 1 month before the first dose;
21. Patients with a history of drug abuse or alcoholism;
22. Patients suffering from mental illness or obvious mental disorders, or incapacity or cognitive inability due to other causes;
23. Patients who have fertility plan or sperm donation plan during the whole trial period and within 3 months after administration, or are unwilling to take effective physical contraception measures (such as condom, diaphragm, intrauterine device);
24. Patients who have clinically significant diseases or other reasons that, in the opinion of the investigator, make participation in the clinical trial inappropriate (e.g., patients who cannot benefit from the clinical trial);
25. Subjects who, in the opinion of the investigator, have poor compliance that are not evaluable for efficacy or are expected to have a low likelihood of completing the intended course and follow-up.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Lili Xu; +8618518760326; lilixu@gensciences.cn

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT06010953
• Other Study ID Numbers: SS-109-I02
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jiangsu Gensciences lnc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Jiangsu Gensciences lnc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Jiangsu Gensciences lnc.
• Verification Date: November 2023