CRED Understanding Clinical Development 2024

08/10/2024

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SCREENING

Arm C (n=60)

Key eligibility criteria (incl/exclu criteria) • Age (≥18 yrs) • Definition of disease • Stage of disease • Concomitant medication • Risk factor • Prior disease • Biomarker positive

N=240 1:1:1:1

Single PE Arm C vs Arm A

Q2W dosing devostatin – Dose 2

24 weeks

Tapering of con-med

Confirmatory / Pivotal Ph 3

Arm A (n=325)

Q2W dosing devostatin Placebo

52 weeks

N=650 1:1

Arm B (n=325)

Q2W devostatin – Dose 2

52 weeks

Single PE Placebo vs Arm C vs Arm A

Stratification: • Disease severity (moderate/severe) • Biomarker status (+ve/ve)

Key SE: Clinical improvement (PRO); number of AE’s; PK/PD relationship; QOL

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ADAPTIVE DESIGN – SEAMLESS Ph 2 / Ph 3

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Adaptive design – Advantages and Challenges

Advantages of adaptive design of trials:

● Such a design has the potential to speed up the process of drug development (Seamless transition from Phase II to Phase III)

● Adaptation of design specifications with minimal requirements

Sample size reassessment

●

● Discontinue redundant treatment arms – drop non-efficacious doses

Disadvantages of adaptive design of trials:

● Interim analysis could introduce bias

– Design modifications based on the results of an interim analysis

– Little flexibility to modify/change the primary endpoint

● The importance of confidentiality of interim results

– Independent drug monitoring committee (IDMC) – a ‘firewalled’ group likely to be required

POTENTIAL BIAS

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