Optimizing Clinical Endpoints for Phase III Design

The challenge

A biopharmaceutical company developing a therapy for a rare genetic disorder had completed a Phase II study and was planning a Phase III trial. Based on regulatory feedback, the U.S. Food and Drug Administration (FDA) recommended revisiting the trial’s primary endpoint to better reflect clinically meaningful change. Specifically, the sponsor needed to refine the Clinical Global Impression–Severity (CGI‑S) and Clinical Global Impression–Improvement (CGI‑I) scales by incorporating condition‑specific anchors to support assessment of symptom severity at baseline and clinically meaningful improvement over time for clinicians and caregivers, consistent with regulatory expectations.

The team sought expert Medical Affairs support to ensure the updated endpoints were scientifically robust, clinically meaningful, and suitable to inform both regulatory interactions and late‑stage study design.

The Acumetis approach

Acumetis Medical Affairs partnered with the client to generate evidence‑based insights to inform refinement of the CGI scales and strengthen the Phase III design. The approach combined structured evidence review with targeted stakeholder input to ensure endpoints reflected meaningful change within the context of the disease.

Key elements of the work included:

Targeted literature review

First, we performed a comprehensive literature review to understand the extent CGI-I has been used to record clinically meaningful change in other neurological and neurodevelopmental diseases, including the relationship between CGI-I score and clinically meaningful thresholds.

Healthcare provider insight generation

Clinicians were engaged through qualitative one‑on‑one interviews and a facilitated live working group. Findings from the literature review were shared to anchor discussion and support informed input.

Defining clinically meaningful change

Engagements focused on defining minimally clinically meaningful change and clinically meaningful improvement from the perspectives of healthcare providers and caregivers within the specific rare disease context.

Endpoint refinement and scale modification

Insights from interviews and the working group were used to refine condition‑specific anchors within the CGI‑S and CGI‑I scales. Acumetis collaborated closely with the client to design discussion guides, facilitate sessions, and synthesize findings into clear, regulator‑relevant recommendations.

Practical support and execution

Acumetis managed all aspects of engagement execution, including coordination, facilitation, and reporting. Activities were conducted in line with regulatory and compliance requirements and translated into a tailored summary deck to support discussions with the FDA.

The outcome

The recommendations informed regulatory interactions with the FDA and directly supported refinement of the Phase III study design. By grounding endpoint selection in published evidence and expert clinical insight, the client strengthened the relevance and credibility of its primary endpoint strategy.

Why it worked

• A strategic, adaptable, and collaborative partnership that fostered strong relationships by ensuring the client and their stakeholders received comprehensive support through seamless event management while meeting all regulatory and compliance requirements
• A thoughtful, evidence‑based approach that asked the right questions, challenged assumptions, and focused on clinically meaningful change
• Clear, customized outputs that supported key regulatory discussions and informed Phase III study design
• Seamless planning, facilitation, and execution that ensured stakeholders were engaged effectively while meeting regulatory and compliance requirements
• Medical Affairs expertise that maintained scientific rigor while translating insight into practical, regulator‑relevant recommendations

Acumetis medical affairs team

Acumetis Medical Affairs partners with biopharma teams to know the science and own the narrative, turning scientific strategy, evidence generation, and medical communications into credible stories that shape decisions and build confidence. Our teams anticipate evidence needs early and work across functions to ensure clinical endpoints, evidence plans, and communications are rigorous, relevant, and aligned with regulatory expectations.

To learn how Acumetis medical affairs can support your clinical development strategy, contact us to start the conversation.