ADX-097 for Immunoglobulin A Nephropathy

No longer recruiting at 5 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ADX-097 for individuals with specific kidney conditions: Immunoglobulin A Nephropathy (IgAN), Lupus Nephritis (LN), or Complement Component 3 Glomerulopathy (C3G). The aim is to assess the safety and effectiveness of the treatment when administered as a subcutaneous injection. Suitable candidates for this trial have a diagnosis of one of these kidney conditions, follow a stable treatment plan, and manage their condition with medication. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that ADX-097 is likely to be safe for humans?

Research has shown that ADX-097 is generally safe for people. In earlier studies, participants who received this treatment did not experience major side effects directly caused by the drug. Additionally, there were no signs of harmful immune reactions. These findings suggest that ADX-097 is safe to use, but further research is needed to confirm this in larger groups. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for IgAN?

Unlike the standard of care for Immunoglobulin A Nephropathy, which often includes corticosteroids and immunosuppressive drugs to manage symptoms, ADX-097 offers a novel approach by targeting the disease more directly. Researchers are excited about ADX-097 because it is administered through subcutaneous infusions, potentially offering a more convenient and less invasive alternative to traditional treatments. This innovative delivery method, combined with its unique mechanism of action, could provide a new layer of effectiveness and improve the quality of life for patients with this challenging kidney condition.

What evidence suggests that ADX-097 might be an effective treatment for Immunoglobulin A Nephropathy?

Research has shown that ADX-097, the investigational treatment in this trial, may help with kidney problems. In earlier studies with rats, ADX-097 lowered harmful proteins in urine, suggesting it might protect the kidneys. This treatment targets a part of the immune system linked to these kidney issues, potentially reducing damage. In lab tests, ADX-097 showed promise by focusing on specific immune responses, which is important for conditions like Immunoglobulin A Nephropathy (IgAN). These early results suggest it could be effective, but more studies with people are needed to confirm its benefits. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

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

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

My urine protein levels are high.

My kidney function test shows a score of 30 or higher.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06419205

NCT06419205 | A Phase 2 Study to Evaluate the Safety, ... A Phase 2 Study to Evaluate the Safety, PD, PK, and Clinical Activity of ADX-097 in Participants With IgAN, LN or C3G. ClinicalTrials.gov ID NCT06419205.

2. withpower.com withpower.com/trial/adx-097-for-immunoglobulin-a-nephropathy-c9e2e

ADX-097 for Immunoglobulin A Nephropathy 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 ...

3. kireports.org kireports.org/article/S2468-0249(22)01341-9/pdf

POS-042 C3d-Directed Factor H Targeting Delivers Potent ... Collectively, this data suggests C3d-mediated tissue targeting drives ADX-097 potency and efficacy. Finally, we demonstrate C3d deposition and C3 comple ...

4. q32bio.com q32bio.com/q32-bio-presents-new-preclinical-data-at-the-international-society-of-nephrology-frontiers-meeting-demonstrating-the-therapeutic-potential-of-adx-097/

News Collectively, the study results suggest that C3d-mediated tissue targeting drives ADX-097 potency and efficacy. They demonstrate C3d ...

5. journals.lww.com journals.lww.com/10.1681/ASN.20213210S131b

C3d-Targeted Factor H Achieves Potent Renal ... In the rat PHN model, a single 1 mg/kg dose of ADX-097 inhibits glomerular complement and significantly reduces urine protein- and albumin-creatinine ratios, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06419205

NCT06419205 | A Phase 2 Study to Evaluate the Safety, ... A Phase 2 Study to Evaluate the Safety, PD, PK, and Clinical Activity of ADX-097 in Participants With IgAN, LN or C3G. ClinicalTrials.gov ID NCT06419205.

7. asn-online.org asn-online.org/education/kidneyweek/2024/program-abstract.aspx?controlId=4123429

Kidney Week ADX-097 was well tolerated across all dose levels with no clinically significant drug-related safety findings or ADAs observed. ADX-097 demonstrated a robust PK ...

8. q32bio.com q32bio.com/q32-bio-announces-publication-of-preclinical-data-in-molecular-therapy-demonstrating-the-therapeutic-potential-of-tissue-targeted-complement-inhibitor-adx-097-for-complement-mediated-diseases/

News Q32 Bio has completed a Phase 1 clinical trial of ADX-097 and expects to initiate an open-label Phase 2 renal basket clinical trial this year as ...

9. igan.org igan.org/clinical-trial/q32/

Q32 | IgA Nephropathy Foundation A Phase 2 Study to Evaluate the Safety, Pharmacology, Pharmacokinetics, and Clinical Activity of ADX-097 in Adult Patients with Primary IgA Nephropathy, ...