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

NCT05651061 | Completed Phase 1 DMC

• 1 other identifier: CTR20222792
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (10)

• t½

  Up to 72 hours after SS109 injected

• Cmax

  Up to 72 hours after SS109 injected

• Tmax

  Up to 72 hours after SS109 injected

• AUC0-last

  Up to 72 hours after SS109 injected

• AUC0-72

  Up to 72 hours after SS109 injected

Other Outcomes (4)

• PT

  Up to 72 hours after SS109 injected

• aPTT

  Up to 72 hours after SS109 injected

• TGA

  Up to 72 hours after SS109 injected

Study Arms (1)

Dose cohorts

EXPERIMENTAL

Dose cohorts were designed to evaluate the safety, immunogenicity and PK/PD.

Biological: SS109

Interventions

SS109 BIOLOGICAL

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.

Dose cohorts

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age was 18 to 65 years old，when signing the informed consent form, male;
• Clinical diagnosis of hemophilia A or B (previous or screening period FⅧ activity level≤ 1% or FⅨ activity level≤ 2%), and there is one of the following conditions:
• FⅧ or FⅨ inhibitor level ≥ 5Bu/mL during screening period;
• During the screening period, the level of FⅧ and FⅨ inhibitors was less than 5 Bu/mL and more than 0.6 Bu/mL, but had a high response to factor Ⅷ or IX injection (such as, the patient had a positive history of FⅧ/FⅨ inhibitors, and then the inhibitor level is ≥ 5Bu/mL, after the second infusion of FⅧ/FⅨ);
• No active bleeding symptoms before the first injection;
• Patients can comply with the requirements of the protocol and be willing to complete the study as planned and provide biological samples for test;
• 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

You may not qualify if:

• Patients with known history of hypersensitivity to the investigational drug preparation and any of its components;
• There was hypersensitivity or anaphylaxis after FⅦ or IgG2 injection treatment in the past;
• Patients with FⅦ inhibitor positive or with FⅦ inhibitor positive history in screening period;
• Severe anemia (hemoglobin \< 60g/L);
• Platelet count \< 100 × 109/L；
• 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;
• One or more tests are positive, such as HBsAg, HCV antibody, anti-human immunity for HIV antibody and anti-treponema pallidum specific antibody (TPHA);
• 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.);
• 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);
• 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;
• Receive any product containing FⅦ or FⅦa (plasma derived or recombinate) within 48 hours before the first injection;
• Receive any product containing FⅧ (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;
• 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;
• Patients have received immunomodulator (such as gamma globulin α- Interferon and prednisone\>10mg/d \[and\>7 days\] or similar drugs, except antiretroviral drugs);
• Patients who received whole blood or plasma treatment within 2 weeks before the first injection;

Sponsors & Collaborators

• Jiangsu Gensciences lnc.: lead

Study Sites (10)

Anhui Provincial Hospital

Hefei, Anhui, China

Location

Henan Provincial Cancer Hospital

Zhengzhou, Henan, China

Location

Xiangya Hospital, Central South University

Changsha, Hunan, China

Location

Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

Location

Jiangxi Provincial People's Hospital

Nanchang, Jiangxi, China

Location

The First Affiliated Hospital of Shandong First Medical University

Jinan, Shandong, China

Location

The Second Hospital of Shanxi Medical University

Taiyuan, Shanxi, China

Location

Xi'an Central Hospital

Xi’an, Shanxi, China

Location

Hematology Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

Location

The Second Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, China

Location

MeSH Terms

Conditions

Factor VII Deficiency

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Renchi Yang

  Hematology Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2022
• First Posted: December 14, 2022
• Study Start: December 14, 2022
• Primary Completion: March 31, 2023
• Study Completion: August 15, 2023
• Last Updated: August 22, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (10)