Appendix M. the Points to Consider in the Design and Submission Of

UCDenver Biosafety Application Human Gene Transfer Clinical Trials

IBC Application Number: -HG Please return the completed form and the required supporting documentation electronically to

Documents to Submit:

 A scientific abstract  The proposed informed consent  The proposed Clinical Protocol, including document tables, figures, and any relevant  Letter or certification of registration publications with the NIH (GEMCRIS)  The proposed Investigator’s Brochure with  CV of PI(s) in NIH bio-sketch format any appendices  IBC HGT Protocol Review Form  Summary of preclinical studies conducted (Description of the product) in support of the proposed clinical trial or reference to the specific section of the protocol providing this information.

Section I. Administrative Information FDA IND Number: PRINCIPAL INVESTIGATOR: SPONSOR/GRANT AGENCY: DEPARTMENT/DIVISION: SITE(S) WHERE RESEARCH DRUG PHONE NO: 303-724-5541 Mailstop: PREPARATION AND ADMINISTRATION WILL BE DONE: Email: Drug Preparation CO-INVESTIGATORS: Building (s): Room No. (s):

OTHER PERSONNEL (List those involved in Drug Administration THIS clinical trial): Building (s): Room No. (s):

PROJECT TITLE: Other Committee Reviews, if applicable:

UCDenver Application for Human Gene Transfer Clinical Trials—BSF-003, Rev July 2016 1 UCDenver Biosafety Application Human Gene Transfer Clinical Trials I understand that for any experiment involving the deliberate transfer of recombinant DNA, or DNA or RNA derived from recombinant DNA, into human research participants (Human Gene Transfer), no research participant may be enrolled, until the entire review and approval process has been completed in accordance with all CUDenver Institutional Biosafety Committee and COMIRB requirements and stipulations.

I acknowledge that I am aware of all the requirements and restrictions of the most current for the Human Gene Transfer Clinical trial to be conducted. I accept responsibility for the safe conduct of the clinical trial to be conducted at the CUDenver | Anschutz Medical Campus.

I understand that it is my responsibility to assure that all personnel working on this clinical trial are informed of and trained about any of the potential hazards of the recombinant DNA or gene transfer material, the proper actions for safe use, the appropriate steps to take in case of accidents, spills or exposures and that they are provided with all necessary safety equipment/personal protective equipment and are instructed in its use.

______

Date Signature of Principal Investigator

PLEASE FILL OUT THE REST OF THIS FORM BY ANSWERING ALL SECTIONS APPLICABLE TO THIS PROJECT AT UCDenver.

Please attach additional page(s) if necessary. The responses MUST be specific for clinical trials at CUDenver. You may request assistance from the study sponsor for the appropriate responses to these questions.

UCDenver Application for Human Gene Transfer Clinical Trials—BSF-003, Rev August, 2016 2 UCDenver Biosafety Application Human Gene Transfer Clinical Trials

Section II.

Human gene transfer experiments that may require NIH RAC review in addition to the local IBC review:

Check any and all that apply to this protocol:

______The protocol uses a new vector, genetic material, or delivery methodology that represents a first- in-human experience, thus presenting an unknown risk;

_____ The protocol relies on preclinical safety data that were obtained using a new preclinical model system of unknown and unconfirmed value;

_____ The proposed vector, gene construct, or method of delivery is associated with possible toxicities that are not widely known and that may render it difficult for oversight bodies (i.e. IBC, IRB) involved in the review at an initial site(s) to evaluate the protocol rigorously

If any of these conditions may apply to the protocol, the IBC or IRB may request that the NIH RAC (Recombinant DNA Advisory Committee) conduct a public RAC review. If this is requested, it must occur before the local IBC or IRB proceeds with the review/approval of the protocol.

All HGT clinical trials MUST register with the Office of Science Policy/Office of Biotechnology Activities in the Genetic Modification Clinical Research Information System (GEMCRIS) (http://osp.od.nih.gov/office-biotechnology-activities/biomedical- technology-assessment/hgt/gemcris ) and submit documentation of this registration to the local IBC before the review commences.

UCDenver Application for Human Gene Transfer Clinical Trials—BSF-003, Rev August, 2016 3 UCDenver Biosafety Application Human Gene Transfer Clinical Trials

Section III. A description of the product: Appendix M-1-A

1. A description of the product: Appendix M-1-A a. Describe the derivation of the delivery vector system including the source (e.g., viral, bacterial, or plasmid vector); give specifics (i.e. lentiviral vector with tat, env, gag deleted). Also address the following: i. Is it replication incompetent? ii. Describe the methods for replication competent virus testing, if applicable.

b. Describe modifications (e.g., deletions to attenuate or self-inactivate, encapsulation in any synthetic complex, changes to tropisms, etc.).

c. Include references to any previous clinical experience with this vector or similar vectors.

d. Describe the genetic content of the transgene or nucleic acid delivered i. Including the species source of the sequence ii. Whether any modifications have been made (e.g. mutations, deletions, and truncations). iii. What are the regulatory elements contained in the construct? iv. Describe any other material to be used in preparation of the agent (vector and transgene) that will be administered to the human research subject (e.g., helper virus, packaging cell line, carrier particles)

e. Indicate whether the intended target cells are ex vivo or in vivo a. Describe the intended target cells and transduction efficiency. b. If ex vivo, where will this be done (i.e. sponsor’s facility at “xxxxxxx”, PI’s laboratory in research tower “yyyyyy”)

f. Describe the gene transfer agent delivery method and location (i.e. method of administration: intra-tumor injection during surgery, hepatic artery with an infusion pump, out-patient clinic at “zzzzz” hospital, etc.)

g. Will shedding studies be conducted? Is any vector shedding expected?

h. What measures will be undertaken to mitigate the risks, if any, of contamination by or dissemination of the vector to other patients, health-care workers, family members or the environment (facility, home or community)? (i.e. disinfection procedures, restrictions on demographics of family such as no infants younger than 6 months or immunocompromised persons in the home)

i. Is there a risk of vertical transmission to offspring? a. Will pregnancy tests be performed? UCDenver Application for Human Gene Transfer Clinical Trials—BSF-003, Rev August, 2016 4 UCDenver Biosafety Application Human Gene Transfer Clinical Trials b. Will birth control measures be recommended to subjects? i. For what period of time?

j. List any biological safety cabinet to be used in the preparation of the study drug, with: location: If in university laboratory or UCH pharmacy: serial number ______Date of its most recent certification______

k. What specific protocols are to be followed for the receipt, storage, preparation and disposal of study drug?

l. Explain how safety reporting for all Adverse Events or Serious Adverse Events is to be handled. Who will be responsible for the notification to NIH and the FDA, COMIRB and the IBC?

This space is for Institutional Biosafety Committee Use ONLY

IBC Application Number ______-HG

Application Received by IBC Office Date: ______Reviewer 1 Date: ______Reviewer 2 Date: ______Full Committee Review Date: ______Approved Deferred Disapproved COMIRB # Review Panel & Date ______

UCDenver Application for Human Gene Transfer Clinical Trials—BSF-003, Rev August, 2016 5