A Phase I of SS109 in Hemophilia A or and B With Inhibitors

Hemophilia A With Inhibitor Clinical Trial

Official title:

To Evaluate the Safety, PK/PD and Immunogenicity of SS109 in Hemophilia Patients With Blood Coagulation Factor Ⅷ or Ⅸ Inhibitors After Single Administration, Open Label, Dose Escalation, and Multicenter Phase I Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05651061
• Other study ID #: CTR20222792
• Status: Completed
• Phase: Phase 1
• Start date: December 14, 2022
• Est. completion date: August 15, 2023

Study information

• Verified date: May 2023
• Source: Jiangsu Gensciences lnc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase I study aims to evaluate the safety, PK/PD and immunogenicity of SS109 in hemophilia A or and B with inhibitors. Twenty -seven patients are enrolled in study, and divided into five dose cohorts, from 30μg/kg to 360μg/kg. Dose 1 cohort enrolls three patients, each other dose cohorts enroll six patients. All patients included in the study will continue to be followed up until 28 days after SS109 administration.

Description:

This study is an open label, dose escalation, multicenter clinical trial. The study sets up a science review committee to assess the dose escalation. Serial blood samples for PK/PD analysis will be taken up to 72 hours after SS109 injection. Patients safety will be routinely monitored throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: August 15, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Age was 18 to 65 years old,when signing the informed consent form, male;

2. Clinical diagnosis of hemophilia A or B (previous or screening period F? activity

level= 1% or F? activity level= 2%), and there is one of the following conditions:

• F? or F? inhibitor level = 5Bu/mL during screening period;
• During the screening period, the level of F? and F? inhibitors was less than 5 Bu/mL and more than 0.6 Bu/mL, but had a high response to factor ? or IX injection (such as, the patient had a positive history of F?/F? inhibitors, and then the inhibitor level is = 5Bu/mL, after the second infusion of F?/F?);

3. No active bleeding symptoms before the first injection;

4. Patients can comply with the requirements of the protocol and be willing to complete the study as planned and provide biological samples for test;

5. Be able to understand the procedures and methods of this clinical trial. The patient voluntarily participates and signs by himself or by the impartial witness

Exclusion Criteria:

1. Patients with known history of hypersensitivity to the investigational drug preparation and any of its components;

2. There was hypersensitivity or anaphylaxis after F? or IgG2 injection treatment in the past;

3. Patients with F? inhibitor positive or with F? inhibitor positive history in screening period;

4. Severe anemia (hemoglobin < 60g/L);

5. Platelet count < 100 × 109/L;

6. Patients with abnormal liver and kidney functions: alanine aminotransferase (ALT) or aspartate aminotransferase (AST)= 2.5 times the upper limit of normal value (ULN), or total bilirubin = 1.5 times ULN; or blood creatinine (Cr) = 1.5 times;

7. One or more tests are positive, such as HBsAg, HCV antibody, anti-human immunity for HIV antibody and anti-treponema pallidum specific antibody (TPHA);

8. Except for hemophilia A or B, the coagulation indexes of any other bleeding disease or other diseases are obviously different(such as platelet disease, vitamin K deficiency, etc.);

9. History or symptoms of any previous arterial or venous thromboembolism event (such as atherosclerosis, myocardial infarction, ischemic stroke, transient ischemic attack, deep vein thrombosis or pulmonary hypertension, pulmonary embolism), or patients with history of disseminated intravascular coagulation (DIC);

10. Suffered from serious heart disease, such as unstable angina, congestive heart failure (New York Heart Association, = Grade III), severe arrhythmia (QTc interval>450ms, corrected by Fridericia formula), hypertension (systolic blood pressure = 160 mmHg or diastolic blood pressure = 95 mmHg) not controlled by treatment;

11. Receive any product containing F? or F?a (plasma derived or recombinate) within 48 hours before the first injection;

12. Receive any product containing F? (plasma derived or recombinate) within 72 hours before the first injection; or receive any product containing FIX (plasma derived or recombinate) within 96 hours before administration;

13. Patients have used any anticoagulant, anti-fibrinol solvent, chemical, biological products or traditional Chinese medicine that affect platelet function within one week before the first injection or need to use any anticoagulant, anti-fibrinol solvent during PK/PD period, including non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin;

14. Patients have received immunomodulator (such as gamma globulin a- Interferon and prednisone>10mg/d [and>7 days] or similar drugs, except antiretroviral drugs);

15. Patients who received whole blood or plasma treatment within 2 weeks before the first injection;

16. Patients who have received vaccines within 4 weeks or planned to be vaccinated during the trial before the first injection;

17. Major surgery (such as orthopedic surgery and abdominal surgery) was performed within 1 month before the first injection, or planned to undergo surgery during the study;

18. Patients who have been selected into other clinical trials within 1 month before the first injection;

19. Patients with a history of drug abuse or alcohol abuse (alcohol abuse standard: male with a long-term alcohol consumption history of more than 5 years, equivalent to alcohol = 40g/d, = 20g/d for women, or a history of heavy drinking within 2 weeks, with the equivalent alcohol volume > 80g/d.

20. Patients suffering from mental illness or obvious mental disorder, or incapacity and lack of cognition caused by other reasons

21. A birth plan or sperm donation plan from the study to 3 months after the study, or patients are unwilling to take contraceptive measures (such as condoms, diaphragms, intrauterine devices, etc.);

22. A disease with clinical significance or other reasons that the researcher thinks patients are not suitable for participating in this clinical trial (if patients cannot benefit from clinical trials);

23. The investigator considers patients with poor compliance, and patients will be impossible to evaluate the efficacy or accomplish the course of treatment and follow-up.

Related Conditions & MeSH terms

• Factor VII Deficiency
• Hemophilia A
• Hemophilia A With Inhibitor
• Hemophilia B
• Hemophilia B With Inhibitor

Intervention

Biological:
• SS109
27 patients are enrolled in cohorts ,and will continue to be followed up until 28 days after SS109 administration for evaluating safety, PK/PD and immunogenicity.

Locations

Country	Name	City	State
China	Xiangya Hospital, Central South University	Changsha	Hunan
China	Anhui Provincial Hospital	Hefei	Anhui
China	The First Affiliated Hospital of Shandong First Medical University	Jinan	Shandong
China	The Second Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	The Second Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Hematology Hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	Xi'an Central Hospital	Xi'an	Shanxi
China	Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	Henan Provincial Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Gensciences lnc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PT	Prothrombin time	Up to 72 hours after SS109 injected
Other	aPTT	activated partial thromboplastin time	Up to 72 hours after SS109 injected
Other	TGA	thrombin generation test	Up to 72 hours after SS109 injected
Other	TAT	thrombin antithrombin complex	Up to 72 hours after SS109 injected
Primary	The incidence of adverse event/serious adverse event/specical interest adverse event(AE/SAE/AESI)	AE/SAE/AESI is any untoward clinical signs, symptoms or outcomes	Up to 28 days after SS109 injected
Primary	Number of patients with positive FVII inhibitor, anti- drug antibody (ADA)	Number of patients with positive FVII inhibitor, anti drug antibody (ADA)	Up to 28 days after SS109 injected
Secondary	t½	Half-life	Up to 72 hours after SS109 injected
Secondary	Cmax	Maximum concentration	Up to 72 hours after SS109 injected
Secondary	Tmax	Time to reach maximum concentration	Up to 72 hours after SS109 injected
Secondary	AUC0-last	Area under the curve from 0 to last	Up to 72 hours after SS109 injected
Secondary	AUC0-72	Area under the curve from 0 to 72 hour	Up to 72 hours after SS109 injected
Secondary	AUC0-8	Area under the curve from 0 to 8	Up to 72 hours after SS109 injected
Secondary	CL	Clearance	Up to 72 hours after SS109 injected
Secondary	Vd	Volume of distribution	Up to 72 hours after SS109 injected
Secondary	MRT	Mean residence time	Up to 72 hours after SS109 injected
Secondary	IR	Incremental recovery rate	Up to 72 hours after SS109 injected