PS-002 for the Treatment of IgA Nephropathy in Adults

NCT07182227 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: PS-002-1012025-523201-14-00
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 11

Brief Summary

The purpose of the study is to evaluate safety, tolerability, and preliminary effectiveness following administration of PS-002 in adults with primary Immunoglobulin A (IgA) nephropathy. This will be a first-in-human study and will include participants at high risk of disease progression despite receiving current standard-of-care treatment. Participants will be monitored for up to one year after receiving PS-002 and invited to take part in a long-term follow-up study (total follow-up: 5 years).

Conditions

Immunoglobulin A (IgA) Nephropathy

Keywords

Glomerulonephritis; Nephritis; Kidney Diseases; Autoimmune Diseases; Immune System Diseases; IGA

Outcome Measures

Primary Outcomes (1)

• Number of participants with: Treatment-Emergent Adverse Events (TEAEs) and serious TEAEs, TEAEs and serious TEAEs related to PS-002, TEAEs and serious TEAEs related to the PS-002 administration procedure

  Screening up to Week 48

Secondary Outcomes (7)

• Change in proteinuria as measured by Urine Protein:Creatinine Ratio (UPCR) derived from 24 hr urine collection

  Baseline to Week 36

• Change from baseline in proteinuria as measured by urine protein creatinine ratio (UPCR) from spot urine collection. [UPCR (g/g) will be calculated from spot urine collection (first morning void)]

  Baseline to Week 48

• Change from baseline in proteinuria as measured by urine albumin:creatinine ratio (UACR). [UACR (g/g) will be calculated from spot urine collection (first morning void)]

  Baseline to Week 48

• Change from baseline in proteinuria as measured by UACR from 24 hour urine collection. [UACR (mg/day) will be calculated from 24 hour urine collection at Week 36 only]

  Baseline to Week 36

• Change from baseline in creatinine and estimated Glomerular Filtration Rate (eGFR) values calculated using the Chronic Kidney Disease Epidemiology (CKD-EPI) creatinine formula

  Baseline to Week 48

Study Arms (1)

PS-002

EXPERIMENTAL

Part 1: Dose escalation in three groups: Group 1: Low dose, Group 2: Intermediate Dose, Group 3: High Dose. Part 2: Dose expansion in a fourth group with a selected dose.

Genetic: PS-002

Interventions

PS-002 GENETIC

Adeno-associated viral vector containing the human Complement Factor I (CFI) gene

PS-002

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Purespring Therapeutics Limited: lead

Study Sites (11)

University of Miami Hospital

Miami, Florida, 33136, United States

RECRUITING

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

NOT YET RECRUITING

Manchester University NHS Foundation Trust

Manchester, Greater Manchester, M13 9WL, United Kingdom

NOT YET RECRUITING

Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust

Manchester, Greater Manchester, M13 9WL, United Kingdom

RECRUITING

Leicester General Hospital

Leicester, Leicestershire, LE5 4PW, United Kingdom

NOT YET RECRUITING

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

RECRUITING

Southmead Hospital

Bristol, BS10 5NB, United Kingdom

RECRUITING

Cardiff and Vale University Health Board

Cardiff, CF14 4XW, United Kingdom

NOT YET RECRUITING

Royal Infirmary of Edinburgh Clinical Research Facility

Edinburgh, EH16 4SA, United Kingdom

NOT YET RECRUITING

The Royal London Hospital

London, E1 1FR, United Kingdom

RECRUITING

MeSH Terms

Conditions

Kidney Diseases; Glomerulonephritis; Nephritis; Autoimmune Diseases; Immune System Diseases

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Central Study Contacts

Clinical Operations

CONTACT

+44 (0)20 3855 6324; contact@purespringtx.com

Study Design

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

Model Details: Part 1: In the dose exploration of the study, 3 different ascending dose levels will be administered using a sentinel dosing strategy Part 2: Participants will receive the optimal biological dose identified in Part 1 of the study

Study Record Dates

• First Submitted: September 11, 2025
• First Posted: September 19, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029
• Last Updated: March 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); GB (8)