ADX-097 for Immunoglobulin A Nephropathy

Recruiting at 4 trial locations

Overseen By Kristin Orr

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Q32 Bio Inc.

Must be taking: RAAS inhibitors, SGLT2 inhibitors

Disqualifiers: Significant renal disease, uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

Trial Summary

What is the purpose of this trial?

A Phase 2 Study to Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Clinical Activity of ADX-097 Administered Subcutaneously in Male and Female Participants Aged 18 Years or Older With Immunoglobulin A Nephropathy (IgAN), Lupus Nephritis (LN), or Complement Component 3 Glomerulopathy (C3G)

Will I have to stop taking my current medications?

The trial requires that if you are taking a RAAS inhibitor or a sodium-glucose cotransporter-2 (SGLT2) inhibitor, you must have been on a stable dose for at least 12 weeks before starting the study and continue on that stable dose during the study.

What data supports the effectiveness of the drug ADX-097 for treating Immunoglobulin A Nephropathy?

Research on similar treatments, like steroids, shows they can lower the risk of kidney disease progression and reduce protein in urine for patients with Immunoglobulin A Nephropathy. This suggests that immunosuppressive agents, which may include ADX-097, could be promising for treating this condition. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults over 18 with certain kidney conditions: IgAN, LN, or C3G. They should have protein in their urine and a minimum kidney function level. Participants must be on stable doses of specific medications for at least 12 weeks before the study starts.

Inclusion Criteria

Key

I am 18 years old or older.

My kidney disease was confirmed by a biopsy within the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous infusions of ADX-097

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Treatment Details

Interventions

• ADX-097

Trial Overview The trial tests ADX-097, administered subcutaneously (under the skin), to assess its safety and effectiveness in treating IgAN, LN, or C3G. It will also look at how the body processes the drug.

Participant Groups

Group I: Open Label Experimental Treatment 1 Intervention

Subcutaneous Infusions

Who Is Running the Clinical Trial?

Q32 Bio Inc.

Lead Sponsor

Trials

4

Recruited

210+

Findings from Research

Immunosuppressive agents, particularly steroids, significantly lower the risk of progression to end-stage kidney disease (ESRD) in patients with IgA nephropathy, based on a systematic review of 13 trials involving 623 patients.

Alkylating agents were also effective in reducing proteinuria, a key indicator of kidney damage, suggesting that immunosuppressive treatments may be beneficial, although more high-quality studies are needed to determine optimal management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive treatments for immunoglobulin A nephropathy: a meta-analysis of randomized controlled trials. Samuels, JA., Strippoli, GF., Craig, JC., et al.[2022]

In a study of 72 patients with IgA nephropathy presenting with hematuria and minimal proteinuria, 44% experienced adverse clinical events over a median follow-up of 7 years, indicating that this condition is often progressive.

Age at presentation and histologic grade were identified as significant predictors of adverse events, suggesting that older patients and those with more severe histological findings are at higher risk for developing complications like increased proteinuria and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. Szeto, CC., Lai, FM., To, KF., et al.[2019]

In a study of 7 patients with post-transplant immunoglobulin A nephropathy, steroid pulse therapy led to an 85.7% rate of complete remission of proteinuria after 2 years, indicating its efficacy in managing this condition.

The treatment maintained kidney function, as shown by stable estimated glomerular filtration rates, although one patient experienced a herpes zoster infection as an adverse event, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of steroid pulse therapy on post-transplant immunoglobulin A nephropathy. Matsukuma, Y., Masutani, K., Tsuchimoto, A., et al.[2018]

In a review of 15 trials involving 1542 adults with Immunoglobulin A nephropathy, steroid therapy significantly reduced the risk of end-stage renal failure and the doubling of serum creatinine levels.

Steroid treatment also led to a decrease in urinary protein excretion, indicating improved kidney function, with long-term steroid therapy showing greater effectiveness compared to standard or short-term treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steroids in the treatment of IgA nephropathy to the improvement of renal survival: a systematic review and meta-analysis. Zhou, YH., Tang, LG., Guo, SL., et al.[2021]

In a study of 29 patients with immunoglobulin A nephropathy who received alemtuzumab induction therapy and steroid minimization, the recurrence rate of the disease was 27.6%, leading to allograft loss in those affected, which aligns with previously reported rates.

Although patients with immunoglobulin A nephropathy had a higher 1-year rejection rate (24.1% vs 21.4%), there were no significant differences in overall graft or patient survival compared to other transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab Induction and Steroid Minimization in IgA Nephropathy: A Matched-Cohort Analysis. Becker, K., Brooks, J., Mitro, G., et al.[2021]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Immunosuppressive treatments for immunoglobulin A nephropathy: a meta-analysis of randomized controlled trials. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. [2019]

3. Australia pubmed.ncbi.nlm.nih.gov

Effect of steroid pulse therapy on post-transplant immunoglobulin A nephropathy. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Steroids in the treatment of IgA nephropathy to the improvement of renal survival: a systematic review and meta-analysis. [2021]

5. Turkey pubmed.ncbi.nlm.nih.gov

Alemtuzumab Induction and Steroid Minimization in IgA Nephropathy: A Matched-Cohort Analysis. [2021]