First-in-human

This is the most crucial step for any biotech company. Choosing the right CRO partner is crucial for the success of your drug development journey, especially when it comes to the pivotal FIH trial. Your clinical research partner should meet the following criteria: previous experience and expertise, prioritizes participant safety, focus on scientific excellence and accurate clinical data collection. The clinical vendor shall have also a robust project management team, operational and technological capabilities to implement the requested trial design. 

We meet them all!

Our teams in science, regulations, and medical writing can assist with one study or entire clinical research program. We have experts who can support you. We start from tasks like an Investigator’s Brochure (IB) preparation, getting ready for pre-IND meetings, submitting INDs, preparing CTAs, advising on study designs, and writing study protocol. All-in-one services we provide make sure your First-in-Human study starts quicker.

For the bioanalytical component of our study, we prefer partnering with Anapharm Bioanalytics. They provide extensive bioanalytical services to the pharmaceutical, biotech, and generic drug industries globally. Their laboratory is GLP-certified, FDA-inspected, GCP-compliant, and ANVISA-certified, featuring a robust quality system to ensure the delivery of consistent, reproducible, and reliable data essential for international regulatory submissions. With over 30 years of experience in analytical method development, validation, and sample analysis of both small and large molecules, they utilize advanced LC-MS/MS and Ligand Binding Assay (LBA) technology platforms across various biological matrices.

Typically, participants in First-in-human trials are healthy young men, generally between 20 and 40 years old. The selection ensures a more uniform group for investigating the effects of the new drug and reducing variability in the same time. In parallel, these group of healthy subjects are more likely to handle any unforeseen side effects from the drug being investigated. Healthy subjects are those without any health issues that could disrupt the study conduct, complicate the safety or pharmacokinetic data analysis.

• Investigational product tolerance and safety
• Pharmacokinetics or pharmacodynamics 
• Evaluating any effects on subgroup of study subjects based on any demographic factor
• Assessing the therapeutic outcomes in a small group of patients’ specific medical condition

The very first step to FIH clinical trial is IP formulation development. Our experts at Convex can support you throughout our CDMO partners to formulate your preferred dosage form of your investigational product. Simpler dosage forms the better.

We use Fully integrated Electronic Data Capture (EDC) system to ensure participant safety, and the accurate, timely collection of your data.

The aim of First-in-Human (FIH) trials is to find a safe first dose and other important parameters. These trials often start with healthy volunteers receiving only one dose. The investigational dose goes up slowly among different study subjects’ cohorts (called a single ascending dose or SAD study) to see the highest safe dose or any side effects that stop us from increasing the dose further. We usually perform interim analysis of safety data prior to move on to the next dose escalation. After maximum tolerated dose is identified, we move on to the next stage – Multiple Ascending Dose (MAD) study.

In Multiple Ascending Dose (MAD) study the drug is administered multiple times, which support the body reach a steady stat. Again the focus is also at safety and tolerability.

In a First-in-Man (FIM) study, the period a participant stays at the Research unit can vary. It depends on the study protocol and the specific requirements of the trial. Typically, study participants may stay at the investigational site for a few days to a couple of weeks for observation and monitoring after receiving the investigational drug. However, this duration can vary greatly depending on factors such as the nature of the drug being tested, the study design, and the need for intensive monitoring for any potential adverse reactions or side effects. We have run FIM study, whereas healthy volunteers spent 21 on-site days.

We have conducted clinical trials using different methods of delivering investigational products, such as oral, intravenous, intraperitoneal, and transdermal administration, ensuring rapid access. Convex clinical team have also been involved in studies examining the cumulative effects of investigational products.

• Study population selection 

We need to clearly define the specific requirements for healthy volunteers’ participation and integrate very strict inclusion/exclusion criteria. 

• Define the number of subjects per each cohort 

The number of participants in each group is determined by how much the PK (pharmacokinetics) and PD (pharmacodynamics) parameters vary, as well as the goals of the clinical study

• Dosing 

Dose selection/ Route of administration /Dose escalation

• Stopping rules 

The clinical study protocol should outline clear rules for when dosing should be stopped immediately, whether it’s a temporary pause or permanent cessation

• Safety monitoring 

Define strictly the process of reporting adverse events and suspected unexpected serious reactions (SUSARs), among the sponsor and study site.

• Inclusion of a placebo

We speed up the beginning of your FIH trial by starting the planning process for study setup even while your preclinical IND/CTA is being reviewed by regulators. Once the review is done and your study gets the green light from the necessary regulatory bodies, your clinic activities can kick off right away.

One common cause of early drug failure is unforeseen IP toxicity, often linked to the pharmacokinetic (PK) properties of the drug. Unfortunately, this aspect is frequently overlooked. This is why Sponsoring companies of FIM trials should look carefully into preclinical data before entering in human stage.