Protocol 
5 . Human Protocol 
1 . Background 
1.1 Respiratory Manifestations of Cystic Fibrosis 5-2 
1.2 Current Therapy 5-3 
1.3 Rationale for Gene Therapy 5-4 
1.4 Normal and Abnormal Cystic Fibrosis Transmembrane 
Conductance Regulator (CFTR) 5-5 
1.5 CFTR Protein and Its Function 5-5 
1.6 Molecular Pathogenesis of Cystic Fibrosis 5-6 
1.7 Cell Targets for Gene Transfer in Cystic Fibrosis .... 5-6 
1.8 Pathogenesis of the Respiratory Manifestations 
Cystic Fibrosis 5-7 
1.9 Progress Report - New York/NIH 
Human Gene Therapy Study 5-9 
2. AdcvCFTR. 10 
2.1 Construct 5-9 
2.2 Pre-clinical studies 5-9 
2.3 Clinical preparation 5-10 
3. Overall Design of the Clinical Study 5-10 
4. Inclusion/Exclusion Criteria 5-10 
5. Safety and Biologic Efficacy Parameters 
5.1 Safety Parameters 5-12 
5.2 Efficacy Parameters 5-12 
6. Part A 
6.1 Baseline/Part A 5-13 
6.2 Vehicle Control Period/Part A 5-13 
6.3 AdcvCFTR.10 Treatment Period/Part A 5-13 
7. Part B 
7.1 Baseline/Part B 5-15 
7.2 Vehicle Control Period/Part B 5-15 
7.3 AdcvCFTR.10 Treatment Period/Part B 5-15 
8. Part C 
8.1 AdcvCFTR. 10 Treatment Period/Part C 5-16 
9. Additional Issues/Relevant to the Clinical Study 
9.1 Management of Intercurrent Illness 5-17 
9.2 Management of Adverse Effects 5-18 
9.3 Health Care Workers 5-18 
9.4 Environment 5-19 
9.5 Risk-Benefit Considerations for the Patient 5-19 
9.6 Post Study Patient Follow-up 5-20 
9.7 Clinical Facilities for the Study 5-20 
9.8 Privacy and Confidentiality 5-20 
9.9 Reporting of Serious Adverse Effects 5-20 
9.10 Future Directions 5-20 
Recombinant DNA Research, Volume 20 
[195] 
