PS-002 treatment for adults with IgA nephropathy

A Phase 1/2 Multicenter, Open Label, Two-part Study (Single Ascending Dose [Part 1], and Dose Expansion [Part 2]) to Evaluate Safety, Tolerability and Efficacy of PS-002, a Gene Therapy for the Treatment of Adult Participants With Primary IgA Nephropathy

This trial will try a new drug called PS-002 in adults with primary IgA nephropathy who remain at high risk despite standard treatments to check safety, tolerability, and early signs of benefit.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Purespring Therapeutics Limited (Industry-sponsored)
• Drugs / interventions: infliximab, canakinumab, rituximab, cyclophosphamide, prednisone
• Locations: 11 sites (Miami, Florida and 10 other locations)
• Trial ID: NCT07182227 on ClinicalTrials.gov

What this trial studies

This first-in-human Phase 1/2 interventional trial will give PS-002 to adults with biopsy-proven primary IgA nephropathy who have evidence of complement C3 deposition, persistent proteinuria (≥1 g/g or ≥1 g/24 h), and an eGFR ≥45 mL/min/1.73 m2 despite best supportive care. Participants will be monitored closely for safety, tolerability, and preliminary signs of biological activity for up to one year after dosing, with an option for long-term follow-up extending to five years. The study will be conducted at multiple U.S. academic centers and will include regular clinic visits, blood and urine testing, and kidney function monitoring. A typical Phase 1/2 dose-escalation and expansion design will be used to define an acceptable safety profile and initial signals of efficacy.

Who should consider this trial

Good fit: Adults with biopsy-proven primary IgA nephropathy showing C3 deposition, persistent proteinuria of at least 1 g/g (or 1 g/24 h), an eGFR ≥45 mL/min/1.73 m2, controlled blood pressure, and who are receiving best supportive care are the intended participants.

Not a fit: Patients with more advanced kidney dysfunction (eGFR <45 mL/min/1.73 m2), without evidence of complement activity/C3 deposition, with secondary causes of IgA deposition, or with uncontrolled comorbidities are unlikely to qualify or benefit.

Why it matters

Potential benefit: If successful, PS-002 could reduce proteinuria and slow kidney damage, potentially lowering the risk of progression to kidney failure.

How similar studies have performed: Complement-targeting approaches in IgA nephropathy have shown early promise in some clinical programs but remain unproven, and PS-002 is being tested here for the first time in humans.

Eligibility criteria

Inclusion Criteria:

* Diagnosis of primary IgA nephropathy (IgAN) as evidenced by renal biopsy.
* A historic kidney biopsy performed within 36 months prior to screening with reported evidence of complement component 3 (C3) deposition. If the participant had a kidney biopsy performed over 36 months prior to Screening, a new kidney biopsy should be carried out during the Screening period. This biopsy must exhibit signs of ongoing complement system activity.
* Proteinuria as assessed at the Screening visit by UPCR at least 1g/g (at least 1000 mg/g) OR total protein excretion at least 1 g/24 h (at least 1000 mg/24h) sampled from 24 h urine collection.
* eGFR calculated using the CKD-EPI formula at least 45 mL/min/1.73m\^2.
* Sitting office systolic blood pressure equal to or less than 140 mmHg, diastolic blood pressure equal to or less than 90 mmHg.
* All participants must have been on best supportive care for IgAN, as per region-specific requirements defined in the protocol.

Exclusion Criteria:

* A participant has nephrotic syndrome, defined for this purpose as 24 h urine protein greater than 3.5g with concurrent hypoalbuminemia (serum albumin less than 3.0 g/dL \[less than 30 g/L\]).
* Any secondary IgAN defined as associated with gastrointestinal and liver disorders (liver cirrhosis, celiac disease, Crohn's disease, ulcerative colitis), autoimmune disorders (dermatitis herpetiformis, psoriasis, seronegative arthritis, systemic lupus erythematosus, rheumatoid arthritis), malignancy (IgA myeloma, lymphoma, lung cancer, renal cell cancer, cutaneous T-cell lymphoma), respiratory disorders (bronchiolitis obliterans, idiopathic pulmonary fibrosis) etc.
* Having a major concurrent non-IgAN-related disease that, in the opinion of the investigator, prevents the assessment of IgAN.
* History of malignancy; or bone marrow or organ transplant.
* History of, or currently active primary or secondary immunodeficiency, including known history of human immunodeficiency virus infection, and other severe immunodeficiency blood disorders.
* Presence of other significant medical conditions that would create an unacceptable procedure or anesthesia risk.
* Aspartate aminotransferase or alanine aminotransferase greater than 1.5 times the upper limit of normal.
* History of serious infection requiring parenteral antibiotics within the past 8 weeks prior to study drug administration.
* Participants previously treated with immunosuppressive/immunomodulatory agents such as, but not limited to, cyclophosphamide, infliximab, complement inhibitor, canakinumab, mycophenolate mofetil, mycophenolate sodium, cyclosporine, tacrolimus, everolimus, or systemic corticosteroids (exposure greater than 7.5mg/day prednisone/prednisolone equivalent) within 90 days (or 180 days for rituximab) prior to Screening. Participants previously or currently receiving oral budesonide (Kinpeygo/Tarpeyo) require wash out for 90 days prior to the study drug administration.
* Exposed to a live or attenuated vaccine within the 6 weeks prior to study drug administration.
* Participants with a known sensitivity or intolerance to corticosteroid therapy.
* Known hypersensitivity to study drug ingredients.
* Prior treatment with PS-002 or any other gene therapy, or participation in any other investigational trial during this study.
* Positive serology for hepatitis B or C, i.e., positive hepatitis B surface antigen or hepatitis C ribonucleic acid (RNA) viral load positive.
* Participants treated with potentially hepatotoxic medications unless they have been monitored in accordance with the drug label and have received a stable dose since \>90 days prior to dosing without clinically significant liver enzyme fluctuations.

Note: Other protocol-defined inclusion/exclusion criteria may apply.

Where this trial is running

Miami, Florida and 10 other locations

• University of Miami Hospital — Miami, Florida, United States (Recruiting)
• The Johns Hopkins Hospital — Baltimore, Maryland, United States (Recruiting)
• University of Michigan Hospital — Ann Arbor, Michigan, United States (Not_yet_recruiting)
• Manchester University NHS Foundation Trust — Manchester, Greater Manchester, United Kingdom (Not_yet_recruiting)
• Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust — Manchester, Greater Manchester, United Kingdom (Recruiting)
• Leicester General Hospital — Leicester, Leicestershire, United Kingdom (Not_yet_recruiting)
• Nottingham University Hospitals NHS Trust — Nottingham, Nottinghamshire, United Kingdom (Recruiting)
• Southmead Hospital — Bristol, United Kingdom (Recruiting)
• Cardiff and Vale University Health Board — Cardiff, United Kingdom (Not_yet_recruiting)
• Royal Infirmary of Edinburgh Clinical Research Facility — Edinburgh, United Kingdom (Not_yet_recruiting)
• The Royal London Hospital — London, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Clinical Operations

Conditions Immunoglobulin A Nephropathy; Glomerulonephritis; Nephritis; Kidney Diseases; Autoimmune Diseases; Immune System Diseases; IGA