Treatment for anemia in patients with PNH who didn't respond to C5 inhibitors

Multicenter, Single-arm, Open-label Phase III Study to Evaluate Efficacy and Safety of HRS-5965 Capsule in Patients With PNH Who Are Still Anemia After Anti-C5 Antibody Treatment

This study is testing a new treatment called HRS-5965 for people with PNH who are still anemic despite using other medications to see if it can help improve their condition.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chengdu Suncadia Medicine Co., Ltd. (Industry-sponsored)
• Drugs / interventions: ikuzumab, covalimab, ikuzuzumab, covalimamab, Prednisone, eculizumab, Kevacumab
• Locations: 2 sites (Tianjin, Tianjin and 1 other locations)
• Trial ID: NCT06715943 on ClinicalTrials.gov

What this trial studies

This phase III clinical trial evaluates the efficacy and safety of HRS-5965 in patients with paroxysmal nocturnal hemoglobinuria (PNH) who remain anemic despite stable treatment with C5 complement inhibitors. The study involves approximately 35 participants who will receive HRS-5965 capsules after an 8-week screening period, followed by a 24-week treatment phase. The trial is designed as a multi-center, single-arm, open-label study, focusing on patients who have had low hemoglobin levels and may have required red blood cell transfusions prior to enrollment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed PNH who have low hemoglobin levels despite stable use of C5 inhibitors.

Not a fit: Patients who have not been diagnosed with PNH or those who have not received prior treatment with C5 inhibitors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve hemoglobin levels and overall quality of life for patients with PNH who are not adequately managed by existing therapies.

How similar studies have performed: While there have been studies on treatments for PNH, this specific approach using HRS-5965 is novel and has not been extensively tested in previous trials.

Eligibility criteria

Inclusion Criteria:

1. Understand the specific process of the experiment, voluntarily participate in this experiment, and sign a written informed consent form.
2. Age ≥18 on the day of signing the informed consent, regardless of gender
3. It was confirmed to be PNH during screening, and the clone size of red blood cells or granulocytes was detected by flow cytopy \>10%
4. Stable use of C5 complement inhibitor ikuzumab/covalimab for the first 6 months of random treatment
5. The average hemoglobin level of at least two tests in 4 months before screening \< 10 g/dL
6. The average hemoglobin level of two tests in the central laboratory during screening \< 10 g/dL
7. Inoccution of Neisseris meningitis and Streptococcus pneumoniae vaccine at least 2 weeks before the first administration of HRS-5965; if HRS-5965 treatment must begin less than 2 weeks after vaccination, preventive antibiotic treatment must begin at least 2 weeks after vaccination.
8. Male and female subjects with fertility must agree to adopt efficient contraceptive measures with their partners within 30 days from the signing of the informed consent form to the last administration, and have no family planning and no sperm/egg donation.

Exclusion Criteria:

1. In addition to C5 complement inhibitors (ikuzuzumab/covalimamab), those who have participated in clinical trials of any other drug or medical device within 1 month before and are expected to have a residual effect of experimental treatment (judged by researchers), or those who were still in the follow-up period of a clinical trial or the 5 half-life of the experimental drug before screening Inside (whichever is longer)
2. Known or suspected hereditary or acquired complement deficiency
3. Currently active primary or secondary immunodeficiency
4. Those who have a history of splenectomy or plan to perform surgery during the trial
5. History of bone marrow/hematopoietic stem cells or solid organ transplantation
6. Diagnosed malignant tumors in the past 5 years
7. There is laboratory evidence for patients with bone marrow failure during screening
8. History of infection with pod bacteria (such as Neisseris meningitis, Streptococcus pneumoniae, etc.)
9. There is or is suspected of systemic active bacteria, virus or fungal infection 2 weeks before the first administration of HRS-5965 (according to the researcher's judgment)
10. Fever occurs within 1 week before the first administration of HRS-5965 (body temperature ≥38 ℃)
11. Human immunodeficiency virus (HIV) infection
12. Hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCVAb) are positive during screening, or abnormal liver function test during screening
13. Use any of the following drugs, unless there is a stable treatment plan before screening: a) erythropoietin (ESA), hypoxic-inducing factor proaminoyl hydroxylase inhibitor (HIF-PHI) or immunosuppressant for at least 8 weeks b) Systemic use of glucocorticoids (≤15 mg/day Prednisone or equivalent doses of glucocorticoids) at least 4 weeks c) Vitamin K antagonists (such as warfarin) have a stable international standardized ratio (INR) at least 4 weeks d) Low molecular weight heparin, oral anticoagulants such as aspirin, rvaroxaban, apifloxaban, etc. at least 4 weeks e) Iron supplements , vitamin B12, folic acid or androgen for at least 4 weeks
14. During screening, there are serious concurrent diseases, such as severe kidney disease (such as eGFR\<30 mL/min/1.73 m2, dialysis), advanced heart disease (such as NYHA level IV), severe lung disease such as pulmonary hypertension (WHO level IV) or liver disease (such as active hepatitis), etc. , judged by the researcher that it is not suitable to participate in the researcher
15. Any medical condition determined by the researcher that it may affect the patient's participation in the trial, chronic anemia or unstable thrombosis events that may exist for other causes, and other conditions judged by the researcher to be unsuitable for participation in the trial
16. Those who are suspected of being allergic to experimental drugs or any ingredient in experimental drugs
17. Screening positive blood pregnancy test and breastfeeding women at the time of the visit

Where this trial is running

Tianjin, Tianjin and 1 other locations

• Hematology Hospital of Chinese Academy of Medical Sciences — Tianjin, Tianjin, China (Recruiting)
• Tianjin Medical University General Hospital — Tianjin, Tianjin, China (Recruiting)

Study contacts

• Study coordinator: Sheng Qi

Conditions Paroxysmal Nocturnal Hemoglobinuria