CRED Understanding Clinical Development 2024

08/10/2024

Single arm trial

⚫ Will often include a 2-stage design with a planned interim futility analysis.

1 st stage – small number enrolled

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Planned interim futility analysis

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2 nd stage – continue enrolling

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⚫ Early stopping rules are based on key secondary endpoints (toxicity, tolerability, treatment compliance).

Non-comparative randomised trial

⚫ Randomised to >2 experimental arms

⚫ Each experimental arm is strictly compared to historical control

⚫ No control arm

⚫ Arm with highest observed response rate selected for further study

Historical control data

⚫ Limitations

Potential differences in population

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Current standard of Care

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⚫ Frequency and method of disease assessment

The Organisation for Professionals in Regulatory Affairs

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Arm A (n=60)

SCREENING

Q2W dosing Placebo devostatin

Single PE Placebo

24 weeks

Arm B (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

Q2W dosing devostatin – Dose 1

Single PE Arm B vs Arm A

24 weeks

N=240 1:1:1:1

Arm C (n=60)

Q2W dosing devostatin – Dose 2

Single PE Arm C vs Arm A

24 weeks

Arm D (n=60)

Q2W dosing devostatin – Dose 3

Single PE Arm D vs Arm A

24 weeks

Tapering of con-med

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

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

The Organisation for Professionals in Regulatory Affairs

STANDARD DOSE RANGING – PLACEBO RCT

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