Kidney Week

Abstract: FR-PO979

A Phase IIb Randomized, Double-Blind, Placebo-Controlled, Multi-Centre, Dose Ranging Study of Atuliflapon in Participants with Proteinuric CKD

Session Information

• CKD Interventions: Trials and Quality Improvement
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Heerspink, Hiddo Jan L., University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L. Heerspink,

• Ufnal, Marcin, AstraZeneca R and D, Warsaw, Poland

Marcin Ufnal,

• Law, C Gordon, Early Biometrics & Statistical Innovation, R&D, AstraZeneca, Gaithersburg, Maryland, United States

C Gordon Law,

• Whatling, Carl A., AstraZeneca R and D, Gothenburg, Sweden

Carl A. Whatling,

• Ericsson, Hans Ingemar, AstraZeneca R and D, Gothenburg, Sweden

Hans Ingemar Ericsson,

• Knöchel, Jane, AstraZeneca R and D, Gothenburg, Sweden

Jane Knöchel,

• Connolly, Kathleen, AstraZeneca R&D Cambridge, Cambridge, United Kingdom

Kathleen Connolly,

• Kinch, Russell James, AstraZeneca R&D Cambridge, Cambridge, United Kingdom

Russell James Kinch,

• MacPhee, Iain, AstraZeneca R&D Cambridge, Cambridge, United Kingdom

Iain MacPhee,

Group or Team Name

• FLAIR Study Investigators.

Background

5-lipoxygenase activating protein (FLAP) is a key component in the synthetic pathway for leukotrienes and thought to contribute to inflammation and CKD progression. We assessed the albuminuria lowering effect of Atuliflapon (AZD5718), a reversible FLAP inhibitor.

Methods

Participants with proteinuric CKD: eGFR 20 -75 mL/min/1.73m²; uACR 200-500 mg/g were randomised to three doses of Atuliflapon or placebo. Treatment period 1 of 12 weeks on existing standard of care (SOC), which included SGLT2i in 25% of the DKD patients, was followed by treatment period 2 where all participants initiated 8 weeks treatment with 10 mg dapagliflozin on top of existing SOC.

Results

A total of 613 participants were randomised. Following the results of an interim analysis the Sponsor decided to terminate the study early based on no significant reduction in uACR compared to placebo after 20 weeks of treatment (Table), at which point 438 had completed treatment period 1 and 318 had completed treatment period 2. Median age was 66 years (range 27-87); 65.8% male; Type 2 DM 76.5%; Median eGFR 40 mL/min/1.73m². The target of 80% suppression of urinary and plasma leukotriene B4 was achieved. The expected reductions in uACR and eGFR on commencing SGLT2i treatment were seen after the addition of dapagliflozin in the second treatment period. There were no significant safety issues.

Conclusion

Atuliflapon did not significantly reduce uACR in any of the treatment groups compared to placebo.

Table

Funding

• Commercial Support – AstraZeneca