TIP-001 - DIVERSITY IN ACTION, CASE STUDIES OF ASTRAZENECA-SPONSORED PHASE-I TRIALS.

C. Bhattacharya¹, K. Thacker², M. McCarthy³, T. Crockett⁴, A. Sawant⁵, C. Riff⁶, L. Bertagnolli⁷, M. Astrand⁶, A. Khan⁸, W. Tang¹, M. Patel^9,10, K. Williams¹¹, J. Harris², M. Gibbs¹²; ¹Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, USA, ²Department of Regulatory Toxicology and Safety Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, UK, Cambridge, UK, ³Projects, Research and Early Development, Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, USA, Gaithersburg, MD, USA, ⁴Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, USA, ⁵Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences AstraZeneca, Waltham, MA, USA, ⁶Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, ⁷Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gaithersburg, MD, USA, ⁸Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA, ⁹Imaging and Data analytics, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK, Cambridge, USA, ¹⁰Mishal`s present affiliation. Corporate Vice President, AI and Digital Research, Digital Science and invocation, Research and early development, NovoNordisk, ¹¹R&D Patient Science, Gaithersburg, Maryland, USA, ¹²Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gaithersburg, USA.

Background: FDA`s Diversity plan guidance aims to ensure registrational studies are inclusive & representative of the target patient population including demographics like race/ethnicity, sex, comorbidities, etc. This requires early dose & exposure/ER assessments that can be extrapolated to target population. We present the AstraZeneca (AZ) approach for clinical pharmacology studies that include specific & diverse populations with the goal to improve generalizability of clinical trials & ensure medical products are safe & effective for all segments of the intended use population.

Methods: 1. Inclusion of underrepresented patient demographic in a Phase 1 study
AZD2373 is an ASO being developed for APOL1-Mediated Kidney Disease (AMKD). Among people of African ancestry, there is an increased risk of CKD & ESKD for those with APOL1 high-risk genotypes compared to those without. A Phase 1, multiple ascending dose trial (NCT05351047) in healthy males with genetic variants of interest but without AMKD (N=24) of West African Ancestry was conducted to assess safety, PK in a population with & without variants of interest.

2. Inclusion of women of childbearing potential (WoCBP)
AZ routinely considers inclusion of WoCBP for all assets from Phase 1 onwards. Each program is considered on case-by-case basis applying what is known about DART implications of modality, chemistry, target biology & non-clinical data. These are integrated into a risk:benefit analysis driven by target disease & patient demographics. Aligned with international territory & ICH guidelines, WoCBP are included at earliest appropriate opportunity. Contraception & pregnancy testing requirements are defined & aligned with known data to mitigate potential risks. This is illustrated by inclusion of WoCBP in AZD4604 (NCT06157255) in Phase 1 & anifrolumab, where a trial to explore effects on pregnancy outcomes & milk transfer is being planned.

3. Inclusive renal impairment (RI) studies
AZ developed a physician-based network leveraging RWD (claims & EHR) to optimize RI studies by understanding physician referral patterns & patient flow. This allows mapping patients across areas & enrolment of diverse populations.

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Design: We show how early inclusion of under-represented populations may support a diverse target population in registration trials & equitable healthcare