Exploratory Clinical Trial (ECT)

An Exploratory Clinical Trial (ECT) is a Clinical Trial that is performed prior to dose escalation and safety and tolerability trials.

• AKA: Safety and Tolerability Clinical Trial.
• Context:
  • It is usually classified as a Phase I Clinical Trial, but it can be classified occasionally as a Phase 0 or a Phase II Clinical Trial.
  • It is focused on clinical safety and tolerability.
• Example(s):
  • An Exploratory Clinical Study of LDP Combined With CDP1 in Patients with Advanced Malignant Tumor,
  • Exploratory Clinical Trial with Rhodiola Rosea Extract in Patients Suffering from Burnout Symptoms,
  • Exploratory Clinical Trial on the Safety and Bactericidal Effect of 222-nm Ultraviolet C Irradiation in Healthy Humans,
  • …
• Counter-Example(s):
  • Adaptive Clinical Trial,
  • Confirmatory Clinical Trial,
  • Explanatory Clinical Trial,
  • Pragmatic Clinical Trial.
• See: First-In-Human (FIH) Clinical Trial, Decentralized Clinical Trial, Correlation, Therapy, Outcomes Research, Health System, Causality, Confounding, Drug Clinical Trial, Medical Device Clinical Trial, Clinical Procedure Trial, Observational Clinical Trial, Interventional Clinical Trial, Clinical Trial Management System, Clinical Trial Monitoring System, Clinical Trial Protocol, Clinical Trial Design System, Clinical Endpoint.

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References

2019

• (EMA/CAT, 2019) ⇒ Committee for Advanced Therapies (2019). "Draft guideline on quality, non-clinical and clinical requirements for investigational advanced therapy medicinal products in clinical trials". EMA/CAT/852602/2018.
  • QUOTE: For exploratory trials, especially for the First-in-human trials, the primary objectives are the safety and tolerability.

    The design of exploratory trials of ATIMPs often involves consideration of clinical safety issues different from other medicinal products (including extended or permanent adverse effects, e.g. long-term or delayed safety issues, such as infections, immunogenicity/immunosuppressant, integration into the genome of some GTIMPs, ectopi tissue formation and malignant transformation). Other objectives of exploratory trials are:

    • pharmacokinetics and biodistribution;
    • identification and characterisation of the manufacturing and administration issues that can influence the product development;
    • assessment of pharmacodynamics, early measurement of drug activity e.g. gene expression, cell engraftment;
    • assessment of the feasibility of recruitment, treatment approach and the use of the ATMP;
    • dose selection and determination of recommended dose for confirmatory studies.

First-in-human (FIH) studies are a subset of exploratory studies, when the ATIMP is the first time translated from non-clinical studies to humans. The design of FIH clinical trials with ATIMPs deserves specific considerations. For example, the extrapolation from non-clinical pharmacodynamic, pharmacokinetic/biodistibution and toxicity data to the human situation may be limited, depending on the relevance of the non-clinical animal model(...)

 Exploratory studies with ATIMPs are often designed as phase I/II trials, combining features of phase I and phase II design. Examples are trials with GTMPs in patients with monogenetic disease, where dose escalation and determination of a recommended dose is followed by an extension phase, to include additional patients on the recommended dose level and to further explore the efficacy of the GTMP. The trial protocol should define the methodology to move from the dose-escalation phase to the extension phase, and how this is captured in a substantial amendment.

2009

• (Francillon et al.,2009) ⇒ Alain Francillon, Gisele Pickering, and Chantal Belorgey (2009). "Exploratory clinical trials: implementation modes & guidelines, scope and regulatory framework". In: Elsevier - Therapie, 64(3), 155-159. DOI:10.2515/therapie/2009022.
  • QUOTE: To avoid confusion, it is preferable to refer to an “exploratory trial” rather than use the ambiguous term “Phase 0 trials”. Exploratory trials are clinical trials performed early in Phase I, prior to dose escalation and safety and tolerability trials. These trials are de facto first-in-human studies but lack a therapeutic or diagnostic goal. Furthermore, they seek to specify the IMP’s pharmacokinetics and/or pharmacology rather than to establish (as in conventional Phase I trials) the maximum tolerated dose (MTD). The objective is to answer specific questions which condition the continuation or suspension of the candidate drug development program. For example, an IMP can be eliminated very early on if exploratory trials reveal poor pharmacodynamic and/or pharmacokinetic properties (rapid clearance, low bioavailability, absence of effect on the target, etc.).

     These trials feature a small number of patients or healthy subjects exposed over a short period of time to a low dose of an investigational medicinal product. Exploratory trials are not substitutes for conventional Phase I trials. An exploratory trial is only performed when it is a justified step, is useful in product development, complies with prerequisites and ensures the safety of the participants. </s

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