Therapeutic Product Immunogenicity Community

Hi Community,

Would you help me improve my understanding on how to correctly assign IMG as a secondary vs. exploratory objective?  Throughout my career, I have supported studies where immunogenicity is an exploratory objective, we used a validated method and reported in the CSR, in order words, treated as we would a secondary objective. Recently, when questioned about this, I was not able to properly justify why it was not a secondary objective. In other cases, based on immunogenicity risk assessment, we have purposely placed immunogenicity under exploratory objectives because we do not intend to analyze unless we see an unexplained change in PK/safety.  That aligns with this NIH reference (Endpoint (nih.gov)) see below. Also, for programs in life cycle management, exploratory makes sense, since there is so much data on IMG. For a FIH, can you think of why you would place under exploratory? Any other thoughts? Thanks so much for sharing your experiences.

From the NIH link:  Exploratory endpoints may include clinically important events that are expected to occur too infrequently to show a treatment effect or endpoints that for other reasons are thought to be less likely to show an effect but are included to explore new hypotheses.

Hi Johanna, 

For the most part I've always had immunogenicity as a secondary endpoint, and I don't think we ever articulated in any of the companies I've worked in why that should be. Regardless of whether primary endpoints were met we still evaluated immunogenicity. For humanized monoclonal antibodies, in general, it fits in with exploratory objectives as defined by the NIH reference since it tends to occur infrequently, or is less likely to show an effect (given the level of sensitivity in our current assays). It seems to have a greater importance to the understanding of results than an exploratory endpoint suggests, especially as related to safety or altered PK. The few instances where it would have been an exploratory endpoint is in lifecycle management or Ph3 trials where we have a really good understanding of it's prevalence/incidence/impact. Early on, in the experiences I've had, it's been a secondary endpoint. 

I too would like to hear what others have experienced. 

Hi Community,

Would you help me improve my understanding on how to correctly assign IMG as a secondary vs. exploratory objective?  Throughout my career, I have supported studies where immunogenicity is an exploratory objective, we used a validated method and reported in the CSR, in order words, treated as we would a secondary objective. Recently, when questioned about this, I was not able to properly justify why it was not a secondary objective. In other cases, based on immunogenicity risk assessment, we have purposely placed immunogenicity under exploratory objectives because we do not intend to analyze unless we see an unexplained change in PK/safety.  That aligns with this NIH reference (Endpoint (nih.gov)) see below. Also, for programs in life cycle management, exploratory makes sense, since there is so much data on IMG. For a FIH, can you think of why you would place under exploratory? Any other thoughts? Thanks so much for sharing your experiences.

From the NIH link:  Exploratory endpoints may include clinically important events that are expected to occur too infrequently to show a treatment effect or endpoints that for other reasons are thought to be less likely to show an effect but are included to explore new hypotheses.