Design the study around the evidence you need next
A proof-of-concept clinical trial examines whether an investigational treatment demonstrates biological or clinical activity consistent with the proposed mechanism of action in the target patient population. Often conducted in Phase Ib or Phase IIa, these studies build on early safety, PK and PD findings to inform subsequent development decisions.
The study design should ensure that endpoints, biomarkers and clinical assessments are capable of detecting a meaningful treatment signal within the constraints of an early development programme.
The value lies in generating evidence that can be interpreted in context. The findings may support progression, indicate that the dose, regimen, population or endpoints need refinement, or show that further evidence is required before a larger clinical trial.
We help sponsors connect development strategy with study feasibility and delivery, so key assumptions and operational risks are considered before the protocol is finalised. Support can extend from protocol and regulatory planning through study start-up, clinical delivery, data management, statistical analysis and interpretation, with the scope shaped around the needs of each programme.
Align every design choice with the clinical hypothesis
In a proof-of-concept study, the population, dose, endpoints, assessment schedule and analysis need to work together. Each decision affects whether a treatment signal can be detected and interpreted in the context of the study objectives.
Clinical hypothesis
Clarify what the study needs to assess and how the resulting evidence will inform the development strategy.
Patient population
Identify patients in whom the question can be answered without making the eligibility criteria unnecessarily restrictive or difficult for sites to deliver.
Dose and regimen
Connect the available safety, PK and PD evidence with the dose levels, treatment duration and dosing schedule selected for the study.
Endpoints and biomarkers
Select assessments that reflect the expected effect and can be measured reliably at the required time points and across participating sites.
Analysis and decision
Define how the results will be analysed and interpreted, including which findings would support progression and which uncertainties may require further evidence.
Build patient and site feasibility into the protocol
A proof-of-concept design can be scientifically sound and still be difficult to deliver. Eligibility criteria, visit burden, treatment duration, endpoints and specialised assessments all affect whether the right patients can be recruited and evaluated consistently.
We assess these demands against patient availability, investigator experience and site capabilities across Europe. Feasibility, site selection, recruitment planning, study preparation and ongoing oversight are connected to support consistent assessments and reduce avoidable operational variability that could obscure the findings.
Case study: Phase II proof-of-concept study in moderate-to-severe asthma
Clarenta supported patient recruitment and clinical monitoring across three Bulgarian sites participating in a Phase II proof-of-concept study in adults with moderate-to-severe asthma.
The sites enrolled 48 participants, with the leading site recruiting 29 against a contractual target of 15, exceeding the target by 93%. The period from first to last screening was 7.5 months.
Proof-of-concept clinical trial FAQs
A proof-of-concept clinical trial evaluates whether an investigational treatment produces the expected biological or clinical activity in patients. It generates early evidence to inform further development, but is not intended to provide definitive confirmation of efficacy.
A proof-of-concept study is often conducted in Phase Ib or Phase IIa, although the terminology and timing vary by product and development strategy. The study phase should be determined by its objectives and design rather than the PoC label alone.
A first-in-human study involves the initial administration of an investigational product to people and usually focuses on safety, tolerability, PK and dose escalation. A PoC study generally evaluates early biological or clinical activity in patients. Some early clinical trials may combine both types of objectives.
Sponsors should consider scientific and therapeutic expertise, patient and site feasibility, protocol and statistical capabilities, operational delivery and the ability to coordinate endpoints, biomarkers, PK/PD data and analysis. The CRO should also communicate clearly where evidence is strong, uncertain or incomplete.