Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hello All:

It is common to initiate and enable rational clinical combinations specifically in oncology drug development, of investigational drugs with commercially available drugs that may offer either an additive or synergistic effect to the target patient population. 

For early phase 1b type proof of concept combination clinical studies that can be conducted under the parent IND of an investigational drug, I have the following questions to our community: 

1. What are the basic IND amendment requirements to enable such a combo study (e.g. draft protocol and executive summary)? 
2. Does FDA expect the sponsor to amend existing IND sections (e.g. 2.4., 2.5., 2.6, 2.7, Module 4) with the supportive nonclinical and clinical datasets and discussions, or would an integrated executive summary in module 1 of the data and literature supporting the combination suffice? 

Best,
RA

In early stage, you likely do not need too much. Of course you would need a  protocol and you would need to change your IB (typically if adding commercial product you can just add commercial label as addendum to IB) plus ICF of course.  You do not need to revise the aforementioned sections to just add information on the commercial product (as most critical information in label). If you have any nonclinical information on the combo, then you would want to add that to the appropriate sections. Of course best to run by your RPM.


------------------------------
Robert Blanks RAC
VP, Regulatory Affairs and Quality Assurance
[Ardelyx]
Auburndale MA
United States
------------------------------

Original Message:
Sent: 23-Jul-2021 11:49
From: Anonymous Member
Subject: IND amendments - enabling drug-drug combination studies

This message was posted by a user wishing to remain anonymous

Hello All:

It is common to initiate and enable rational clinical combinations specifically in oncology drug development, of investigational drugs with commercially available drugs that may offer either an additive or synergistic effect to the target patient population.

For early phase 1b type proof of concept combination clinical studies that can be conducted under the parent IND of an investigational drug, I have the following questions to our community:

1. What are the basic IND amendment requirements to enable such a combo study (e.g. draft protocol and executive summary)? 
2. Does FDA expect the sponsor to amend existing IND sections (e.g. 2.4., 2.5., 2.6, 2.7, Module 4) with the supportive nonclinical and clinical datasets and discussions, or would an integrated executive summary in module 1 of the data and literature supporting the combination suffice? 

Best,
RA

This message was posted by a user wishing to remain anonymous

Thank you for your reply. If a sponsor want's FDA feedback on in its combo amendment approach, is there a more expeditious mechanism to obtain feedback, as opposed to filing a formal meeting request. For example,  filing an IND amendment, or will this lead to clinical hold if FDA disagrees with the amendment justification?
Original Message:
Sent: 26-Jul-2021 10:39
From: Robert Blanks
Subject: IND amendments - enabling drug-drug combination studies

In early stage, you likely do not need too much. Of course you would need a  protocol and you would need to change your IB (typically if adding commercial product you can just add commercial label as addendum to IB) plus ICF of course.  You do not need to revise the aforementioned sections to just add information on the commercial product (as most critical information in label). If you have any nonclinical information on the combo, then you would want to add that to the appropriate sections. Of course best to run by your RPM.


------------------------------
Robert Blanks RAC
VP, Regulatory Affairs and Quality Assurance
[Ardelyx]
Auburndale MA
United States

Original Message:
Sent: 23-Jul-2021 11:49
From: Anonymous Member
Subject: IND amendments - enabling drug-drug combination studies

This message was posted by a user wishing to remain anonymous

Hello All:

It is common to initiate and enable rational clinical combinations specifically in oncology drug development, of investigational drugs with commercially available drugs that may offer either an additive or synergistic effect to the target patient population.

For early phase 1b type proof of concept combination clinical studies that can be conducted under the parent IND of an investigational drug, I have the following questions to our community:

1. What are the basic IND amendment requirements to enable such a combo study (e.g. draft protocol and executive summary)? 
2. Does FDA expect the sponsor to amend existing IND sections (e.g. 2.4., 2.5., 2.6, 2.7, Module 4) with the supportive nonclinical and clinical datasets and discussions, or would an integrated executive summary in module 1 of the data and literature supporting the combination suffice? 

Best,
RA

Original Message:
Sent: 7/28/2021 3:10:00 PM
From: Anonymous Member
Subject: RE: IND amendments - enabling drug-drug combination studies

This message was posted by a user wishing to remain anonymous

Thank you for your reply. If a sponsor want's FDA feedback on in its combo amendment approach, is there a more expeditious mechanism to obtain feedback, as opposed to filing a formal meeting request. For example,  filing an IND amendment, or will this lead to clinical hold if FDA disagrees with the amendment justification?
Original Message:
Sent: 26-Jul-2021 10:39
From: Robert Blanks
Subject: IND amendments - enabling drug-drug combination studies

In early stage, you likely do not need too much. Of course you would need a  protocol and you would need to change your IB (typically if adding commercial product you can just add commercial label as addendum to IB) plus ICF of course.  You do not need to revise the aforementioned sections to just add information on the commercial product (as most critical information in label). If you have any nonclinical information on the combo, then you would want to add that to the appropriate sections. Of course best to run by your RPM.


------------------------------
Robert Blanks RAC
VP, Regulatory Affairs and Quality Assurance
[Ardelyx]
Auburndale MA
United States

Original Message:
Sent: 23-Jul-2021 11:49
From: Anonymous Member
Subject: IND amendments - enabling drug-drug combination studies

This message was posted by a user wishing to remain anonymous

Hello All:

It is common to initiate and enable rational clinical combinations specifically in oncology drug development, of investigational drugs with commercially available drugs that may offer either an additive or synergistic effect to the target patient population.

For early phase 1b type proof of concept combination clinical studies that can be conducted under the parent IND of an investigational drug, I have the following questions to our community:

1. What are the basic IND amendment requirements to enable such a combo study (e.g. draft protocol and executive summary)? 
2. Does FDA expect the sponsor to amend existing IND sections (e.g. 2.4., 2.5., 2.6, 2.7, Module 4) with the supportive nonclinical and clinical datasets and discussions, or would an integrated executive summary in module 1 of the data and literature supporting the combination suffice? 

Best,
RA