Amendment #1 to Clinical Research Organization Services Agreement Protocol # ORA-D-015 between Oramed, Inc. and Integrium, LLC
Exhibit 10.1
CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THIS EXHIBIT BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) WOULD LIKELY CAUSE COMPETITIVE HARM TO ORAMED PHARMACEUTICALS INC. IF PUBLICLY DISCLOSED. OMISSIONS ARE DENOTED IN BRACKETS THROUGHOUT THIS EXHIBIT.
| Integrium, LLC. | Confidential |
Amendment #1 to Clinical Research Organization Services Agreement
Protocol # ORA-D-015
between Oramed, Inc. and Integrium, LLC
BASIC PROVISIONS
Study Title: (the “Study”): “A Placebo-controlled, Multi-center, Randomized, Phase 2b Study to Evaluate the Efficacy and Safety of ORMD-0801 in Type 2 Diabetes Mellitus Patients with Inadequate Glycemic Control on Oral Therapy”
Protocol: # (the “Protocol”): ORA-D-015, Amendment #3 dated April 4, 2019
Purpose of Amendment: Revise the contract to reflect two Protocol Amendments, which includes the following changes:
| ● | Subject number has increased as follows |
| ○ | Cohort A (the original contract through Protocol Amend #2) increased from 445 screened to 545 screened |
| ○ | Cohort B (added in Protocol Amend #3) added 145 patients screened |
[+]
| ● | Sites: |
| ○ | Cohort A: 39 Sites |
| ○ | Cohort B: 26 Sites |
| ● | Protocol Amendment 1,2 added the activities below: |
| ○ | Writing of 2 Protocol Amendments |
| ○ | Writing of 2 ICF Amendments |
| ○ | 8-month delay in timeline increasing project management, site management, medical monitoring, data management and EDC support management |
| ■ | a 3.5-month enrollment hold due to a drug delay |
| ■ | a 4.5 month increase in enrollment due to limited drug supply and addition of placebo arm |
| ○ | Regulatory processing of 2 Protocol Amendments, IRB submission |
| ○ | Creation of CSA amendments for the sites |
| ○ | Creation of 23 additional eCRF pages to replace electronic diary, screen programming and UAT testing |
| ○ | Increased eCRF pages per complete subject from 106 to 129 increasing data management tasks |
| ○ | Increase in EDC platform fees for 8 months |
| ○ | Increase in printing to print paper diaries |
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 1 |
| Integrium, LLC. | Confidential |
| ● | Protocol Amendment #3 added the activities below: |
| ○ | Writing of 1 Protocol Amendment |
| ○ | Regulatory Processing of 1 Protocol Amendment, IRB submission |
| ○ | Revision of the IWRS system causing a 1.5-month screening delay |
| ○ | Addition of 3 months of enrollment to enroll the subjects as stated above in 26 active sites |
| ○ | Increase in the number of monitoring visits to monitor the additional subjects |
| ○ | Separate Database lock for Cohort A and an additional lock for Cohort B |
| ○ | Revision to the SAP and the increase in SAS datasets and TLGs, per Ken |
| ○ | Increase in Investigator Grants |
| ○ | Increase in IRB processing pass-through fees |
| ○ | Increase in EDC platform fees for 4.5 months |
Study Timeline: Study timeline increased by 12.5 months
| ● | Cohort A: 8 months |
| ● | Cohort B: 4.5 months |
Projected Time Period of the Services: Effective from November 1, 2017 to May 15, 2020.
Study Specifications Document: Attached Exhibit 2
Revised Study Budget/Payment Schedule:
(a) Revised Budget: Attached Exhibit 3
| Original Contract | Amendment #1 | Revised Total | |
| Service Fees | $[+] | $[+] | $[+] |
| Grants/Site Expenses | $[+] | $[+] | $[+] |
| Pass-through Expenses | $[+] | $[+] | $[+] |
| Total Cost | $[+] | $[+] | $[+] |
(b) Revised Payment Schedule/Advanced Payments: Payments will be made based on the revised payment schedule, Exhibit 4. All previous payments made by Oramed under the Contract Research Organization Services Agreement will be credited and reconciled with the value of this Amendment #1.
All other provisions of the Service Order shall remain unchanged and in effect.
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 2 |
| Integrium, LLC. | Confidential |
This Amendment #1 (“First Amendment”) to the Contract Research Organization Agreement (the “Agreement”) made this 18th day of April, 2019, by and between Oramed Ltd. (“Sponsor”), an Israeli company, with principal offices located at Hi-Tech Park 2/4 Givat-Ram, P.O. Box 39098, Jerusalem, 91390, Israel (“Sponsor”), and Integrium, LLC., a California limited liability company with its principal place of business located at 14351 Myford Road, Suite A, Tustin, CA 92780 (“Integrium”).
WHEREAS, the Agreement by and between Sponsor and Integrium was effective on November 1, 2017; and
WHEREAS, the parties now enter into this First Amendment to the Agreement for the purposes of amending the contract to reflect certain changes in scope and associated costs as indicated on page one of this First Amendment; and
NOW, THEREFORE, for good and valuable consideration contained herein, the exchange, receipt and sufficiency of which are hereby acknowledged, the parties agree as follows:
1. Service Order
Pursuant to the Agreement, this First Amendment to Agreement is attached to the Agreement, and Integrium and Sponsor each authorize the other party to attach this First Amendment to the Agreement to the Agreement in its possession.
2. Scope of Services
Integrium shall perform services as required for the execution of the “Protocol”, Exhibit “1” and specification of the Services as provided in Exhibit “2”. Further revisions to the Protocol and/or any Project Assumptions may require further revisions to the study budget.
3. Compensation and Payment
3.1 For its performance of the services under this Agreement, Integrium shall receive compensation as set forth in the Budget, Exhibit “3” and Payment Schedule included, Exhibit “4”. All invoices shall be paid within thirty (30) days of invoice date. Integrium shall not be responsible for any Study timeline delays, due to lack of payment or late payment from Sponsor.
3.2 Payments to Integrium shall be made to:
Integrium, LLC
100 E. Hanover Avenue
Suite 401
Cedar Knolls, NJ 07927 USA
Tax ID#: 33-0796857
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 3 |
| Integrium, LLC. | Confidential |
Wiring Information:
Bank of the West
4400 MacArthur Blvd
Suite 400
Newport Beach, CA 92660
Routing/ABA # [+]
Bank Account # [+]
Bank Account Name [+]
4. Timelines
It is acknowledged that Sponsor desires to progress the Study at the maximum speed possible, in a manner consistent with good clinical practices and adherence to FDA regulations. Integrium shall use reasonable best efforts to meet the Timeline for the Study set forth in Exhibit “A”.
5. Representations and Warranties of Integrium
Integrium represents and warrants to Sponsor that all of the representations and warranties made by Integrium in the Agreement are true and correct on the date of this Amendment #1 to the Agreement as if made on the date of this Amendment #1.
IN WITNESS THEREOF, this Service Order has been executed by the parties hereto through their duly authorized officers as of the date set forth above.
| For and on behalf of | For and on behalf of |
| Integrium, LLC | Oramed Ltd. |
| /s/ Jessica Coutu | /s/ Nadav Kidron /s/ Miriam Kidron |
| By: Jessica Coutu | By: Nadav Kidron Miriam Kidron |
| Title: Senior Director, Contract Administration | Title: CEO CSO |
| Date: May 1, 2019 | Date: May 1, 2019 |
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 4 |
| Integrium, LLC. | Confidential |
Integrium/ Oramed
Exhibit 1
Protocol Number: ORA-D-015
Amendment #3
Date: April 4, 2019
(Remainder of Page Intentionally Left Blank)
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 5 |
| Integrium, LLC. | Confidential |
Integrium/Oramed
Exhibit 2
Study Specifications
(Remainder of Page Intentionally Left Blank)
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 6 |
| Integrium, LLC. | Confidential |
Study Specifications Document
| Project Identifiers | |
| Sponsor Company | Oramed Ltd. |
| Protocol Number | ORA-D-015 |
| Protocol Title | A Placebo-controlled, Multi-center, Randomized, Phase 2b Study to Evaluate the Efficacy and Safety of ORMD-0801 in Type 2 Diabetes Mellitus Patients with Inadequate Glycemic Control on Oral Therapy |
| Investigational Product(s) | ORMD-0801 |
| Indication | Type 2 Diabetes Mellitus |
| Therapeutic Area | Metabolic |
| Study Phase | III |
| Sponsor Country | Israel |
| Country Locations | US |
| Study Assumptions | |
| Subjects | |
| # Subjects Screened | [+] |
| % Screen Failure Rate | [+]% |
| # Screen Failures | [+] |
| # Subjects Entering Run-In Phase | [+] |
| % Run-In Failure Rate | [+]% |
| # Run-In Failures | [+] |
| # Subjects Entering Treatment Phase | [+] |
| % Early Termination Rate | [+]% |
| # Early Terminations | [+] |
| # Subjects Complete | [+] |
| Sites | |
| # Sites Identified | [+] |
| Total Sites Cohort A | [+] |
| # Central IRB Sites | [+] |
| # Local IRB Sites | [+] |
| Total Sites Active Cohort B | [+] |
| Enrollment | |
| # Screened/site | [+] |
| # Screened/site/week | [+] |
| # Enrolled/site | [+] |
| # Enrollment Rate (per site/per month) | [+] |
| # Randomized/site | [+] |
| # Randomization Rate (per site/ month) | [+] |
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 7 |
| Integrium, LLC. | Confidential |
| Third Party Vendors | ||
| Meeting Planner | 1 | |
| Central IRB | 1 | |
| Central Lab | 1 | |
| CGM Monitors/Supply Vendor | 1 - Contracted by Sponsor | |
| Centralized CGM Reader Vendor | 1 - Contracted by Sponsor | |
| eDiary/Glucometer Vendor | 1 - Contracted by Sponsor | |
| Product Packaging & Distribution | 1 - Contracted by Sponsor | |
| IWRS | 1 - Contracted by Sponsor | |
| Project Meetings | # Meetings | Assumptions |
| Investigator/CRA Training Meeting | [+] | [+] |
| Launch Meeting | [+] | [+] |
| Sponsor Team Teleconferences | [+] | [+] |
| Internal Team Teleconferences | [+] | [+] |
| CRA Teleconferences | [+] | [+] |
| Monitoring Assumptions | ||
| # CRAs | [+] | |
| # Pre-Study Selection Visits | [+] | |
| # Initiation Visits | [+] | |
| For sites where PI and Study Coordinator do not attend Invest. Mtg | ||
| # Interim Monitoring Visits | [+] | |
| Monitoring Interval (Maximum - weeks) | [+] | |
| # Interim Monitoring Visits/site | [+] | |
| # Additional Days on-site/site | [+] | |
| # 1-day Interim Monitoring Visits | [+] | |
| # Additional Days | [+] | |
| # Close-out Visits | [+] | |
| Safety Assumptions | ||
| SAE rate (%) | [+]% | |
| Estimated # SAEs | [+] | |
| Estimated # Expedited SAEs | [+] | |
| Data Management | ||
| CRF pgs per randomized patient | [+] | |
| Unique CRFs/Subject | [+] | |
| Non-Unique CRFs/Subject | [+] | |
| CRF pgs per early term | [+] | |
| CRF pgs per screen failure | [+] | |
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 8 |
| Integrium, LLC. | Confidential |
| Total CRF Pages | [+] |
| Complete subjects | [+] |
| Early Terms | [+] |
| Screen Failures | [+] |
| Total DM Datasets | [+] |
| Total Edit Checks | [+] |
| Estimated # Total Queries | [+] |
| Estimated # Queries/Patient (1/5 pages) | [+] |
| Manual Coding | |
| # Medical History/Subject | [+] |
| # ConMeds/Subject | [+] |
| # AEs/Subject | [+] |
| Data Transfers | |
| # Sponsor Transfers | [+] |
| test, final | |
| # Lab Transfers | [+] |
| test, monthly, final | |
| # PK Transfers | N/A |
| # Electronic Diary Lab Transfers | [+] |
| test, quarterly, final | |
| # Central CGM Reader Transfers | [+] |
| test, quarterly, final | |
| # IWRS Transfers | No charge, integrated with EDC |
| Statistical Analysis | The following assumptions are estimates. The total number of TLGs will be defined upon the finalization of the Statistical Analysis Plan. An amendment to the budget will be issued at that time, if applicable. |
| # SAS Datasets | [+] |
| Estimated Tables | |
| # Standard and Non-Standard Repeat | [+] |
| # Non-Standard Unique | [+] |
| Estimated Listings | |
| # Standard and Non-Standard Repeat | [+] |
| # Non-Standard Unique | [+] |
| Estimated Graphs | |
| # Standard and Non-Standard Repeat | [+] |
| # Non-Standard Unique | [+] |
| Exploratory Output | |
| # Exploratory Tables | [+] |
| # Exploratory Listings | [+] |
| # Exploratory Graphs | [+] |
| pK Parameters | [+] |
| Post-hoc Analysis | [+] |
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 9 |
| Integrium, LLC. | Confidential |
| EDC – DSG | |||
| Number of Screens | |||
| Unique Screens | [+] | ||
| Redundant Screens | [+] | ||
| Site Patient Activity Duration (Months) | [+] | ||
| Enrollment Duration (Months) | [+] | ||
| Server Activity Duration (Months) | [+] | ||
| Usage Fee/Help Desk Fees | |||
| Product Usage Fee/Month | $[+] | ||
| Intregrium Archiving Pricing | |||
| CD/DVD per site | $[+] | ||
| Clinical Study Report | The budget is based on one draft and one final version of the CSR, assuming there will be no hyperlinking. If hyperlinking and/or additional versions of the CSR are requested, they will be provided at the study hourly rate for the actual additional hours. | ||
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 10 |
| Integrium, LLC. | Confidential |
| Project Timeline | |||
| Project Activity | Date | Month # | Week # |
| Study Start Date | [+] | [+] | [+] |
| Final Protocol Date | [+] | [+] | [+] |
| First Patient enrolled at OCRC | [+] | [+] | [+] |
| EDC Set-Up Complete | [+] | [+] | [+] |
| Investigators' Meeting | [+] | [+] | [+] |
| First Patient Screened | [+] | [+] | [+] |
| First Patient Enter Run-In Period | [+] | [+] | [+] |
| First Patient Enter Part 1 Titration | [+] | [+] | [+] |
| First Patient Enter Part 2 Maintenance | [+] | [+] | [+] |
| Start of Screening Hold | [+] | [+] | [+] |
| End of Screening Hold | [+] | [+] | [+] |
| First Patient Last Visit | [+] | [+] | [+] |
| Additional Full Placebo at CSM with all required documents | [+] | [+] | [+] |
| Additional Full Placebo packaged/ready for shipment to site | [+] | [+] | [+] |
| Last Patient Screened Cohort A | [+] | [+] | [+] |
| Last Patient Enter Run-In Period Cohort A | [+] | [+] | [+] |
| Last Patient Part 1 Titration Cohort A | [+] | [+] | [+] |
| Last Patient Enter Part 1 Cohort A | [+] | [+] | [+] |
| Last Patient Part 2 Maintenance Cohort A | [+] | [+] | [+] |
| Last Patient Last Visit Cohort A | [+] | [+] | [+] |
| Last IMV Cohort A | [+] | [+] | [+] |
| Cohort A Database Lock | [+] | [+] | [+] |
| Cohort A Draft Final TLGs | [+] | [+] | [+] |
| Cohort A Final TLGs | [+] | [+] | [+] |
| Draft CSR | [+] | [+] | [+] |
| Final CSR | [+] | [+] | [+] |
| Estimated IWRS Cohort B Go-live Date | [+] | [+] | [+] |
| First Subject Screened Cohort B | [+] | [+] | [+] |
| First Subject Run-in Cohort B | [+] | [+] | [+] |
| First Subject Randomized Cohort B | [+] | [+] | [+] |
| First Subject Last Visit Cohort B | [+] | [+] | [+] |
| Last Subject Screened Cohort B | [+] | [+] | [+] |
| Last Subject Run-in Cohort B | [+] | [+] | [+] |
| Last Subject Randomized Cohort B | [+] | [+] | [+] |
| Last Subject Last Visit Cohort B | [+] | [+] | [+] |
| Last IMV | [+] | [+] | [+] |
| Database Lock | [+] | [+] | [+] |
| Draft Final TLGs | [+] | [+] | [+] |
| Final TLGs | [+] | [+] | [+] |
| Draft CSR | [+] | [+] | [+] |
| Final CSR | [+] | [+] | [+] |
| CRO End Date | [+] | [+] | [+] |
| Total Project Duration (Months) | [+] | ||
| Months | Weeks | Phase | |
| Start-up | [+] | [+] | I |
| Enrollment | [+] | [+] | II |
| Treatment | [+] | [+] | III |
| LPLV-DBL | [+] | [+] | IV |
| DBL-CRO End | [+] | [+] | V |
| [+] | [+] | ||
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 11 |
| Integrium, LLC. | Confidential |
Integrium/Oramed
EXHIBIT 3
Study Budget
(Remainder of Page Intentionally Left Blank)
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 12 |
| Integrium, LLC. | Confidential |
Study Budget
| STUDY START-UP | UNIT COST | UNITS | MEASURE OF UNIT | TOTAL | |
| 1 | Project Management (Start Up) | $[+] | 5.6 | Month | $[+] |
| 2 | Develop/Finalize Project Management Plan | $[+] | 1 | Plan | $[+] |
| 3 | Project Launch Webcast Meeting/Training | $[+] | 1 | Meeting | $[+] |
| 41 | Study Materials Management | $[+] | 39.0 | Site | $[+] |
| 42 | Source Documentation Development | $[+] | 1.0 | Total | $[+] |
| 43 | Site Identification | $[+] | 41.0 | Site | $[+] |
| 44 | Pre-study Site Evaluation Visit | $[+] | 22.0 | Visit | $[+] |
| 45 | Develop/Finalize CRA Monitoring Plan | $[+] | 1 | Plan | $[+] |
| 46 | Study Manual/Quality Plan | $[+] | 1 | Total | $[+] |
| 47 | Data Management Plan ("DMP") | $[+] | 1 | Total | $[+] |
| 48 | Regulatory Document Collection - Start Up | $[+] | 39.0 | Site | $[+] |
| Reg. Doc. Collection - Protocol Amendments | $[+] | 106.0 | Amend*Site | $[+] | |
| 49 | Investigator Budget/Contract Negotiations | $[+] | 39.0 | Site | $[+] |
| Site CSA Amendments | $[+] | 38.0 | Site | $[+] | |
| 50 | Investigator Meeting and Preparation | $[+] | 1 | Meeting | $[+] |
| 51 | Clinical System Set-Up Configuration/Maintenance | $[+] | 40 | Total | $[+] |
| 52 | Generate Randomization Codes | $[+] | 1 | Randomization | $[+] |
| STUDY START-UP FEES TOTAL | $[+] | ||||
| EDC STUDY START-UP | UNIT COST | UNITS | MEASURE OF UNIT | TOTAL | |
| 17 | eCRF Development | $[+] | 1.0 | Total | $[+] |
| 18 | eCRF Completion Instructions | $[+] | 1.0 | Total | $[+] |
| 19 | Edits Specifications and Programming | $[+] | 1.0 | Total | $[+] |
| 20 | Validate/Test Data Entry Screens (UAT) | $[+] | 1.0 | Total | $[+] |
| 21 | Annotate CRF | $[+] | 1 | Total | $[+] |
| 22 | Clinical Database Development-SDTM Dataset Creation/Documentation | $[+] | 1.0 | Total | $[+] |
| 23 | Platform Study Set-up Fee | $[+] | 1 | Total | $[+] |
| 24 | Database Design and Validation Specifications | $[+] | 1.0 | Database | $[+] |
| 25 | EDC Kick-Off Meeting | $[+] | 1 | Meeting | $[+] |
| 26 | Set-up Standard Data Entry Screens | $[+] | 1.0 | Total | $[+] |
| 27 | Training Session | $[+] | 1 | Study | $[+] |
| 28 | Project Manage all aspects of EDC start-up | $[+] | 1 | Start-up | $[+] |
| 29 | Create Enrollment Screen | $[+] | 1 | Total | $[+] |
| 30 | Integrating EDC System with IWRS System | $[+] | 1 | Total | $[+] |
| 31 | Data Export Programming | $[+] | 35.0 | Dataset | $[+] |
| 32 | Create Custom Reports | $[+] | 1 | Report | $[+] |
| 33 | Register users and maintain passwords for life of study (per user (4 per site + 6 for sponsor)) | $[+] | 162.0 | Per User | $[+] |
| EDC START-UP FEES TOTAL | $[+] |
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 13 |
| Integrium, LLC. | Confidential |
| CLINICAL MONITORING | UNIT COST | UNITS | MEASURE OF UNIT | TOTAL | |
| 34 | Project Management (enrollment phase) | $[+] | 15.6 | Month | $[+] |
| 35 | Project Management (treatment phase) | $[+] | 4.4 | Month | $[+] |
| 36 | Project Management Study (LPLV to DBL) | $[+] | 2.1 | Month | $[+] |
| 37 | Project Management Study (DBL to CRO end) | $[+] | 2.9 | Month | $[+] |
| 38 | Sponsor Team Teleconferences | $[+] | 66.0 | Telecon | $[+] |
| 39 | Internal Team Teleconferences | $[+] | 6 | Telecon | $[+] |
| 40 | CRA Teleconferences | $[+] | 12 | Telecon | $[+] |
| 41a | Trial Master File Cohort A | $[+] | 40 | Site, Gen. File | $[+] |
| 41b | Trial Master File Cohort B | $[+] | 29 | Site, Gen. File | $[+] |
| 42a | Regulatory Document Maintenance Cohort A | $[+] | 897 | Month | $[+] |
| 42b | Regulatory Document Maintenance Cohort B | $[+] | 196 | Month | $[+] |
| 43 | Site Initiation Visits | $[+] | 23 | Site | $[+] |
| 44a | Site Management Cohort A | $[+] | 920 | Site*Month | $[+] |
| 44b | Site Management Cohort B | $[+] | 203 | Site*Month | $[+] |
| 45 | Interim Monitoring Visits - One Day | $[+] | 350 | Visit | $[+] |
| 46 | Interim Monitoring Visits - Additional Day On-site | $[+] | 100 | Day | $[+] |
| 47 | Close-out Visits | $[+] | 39.0 | Visit | $[+] |
| 48a | Site Grant Administration Cohort A | $[+] | 20.0 | Month | $[+] |
| 48b | Site Grant Administration Cohort B | $[+] | 5.0 | Month | $[+] |
| CLINICAL MONITORING/LOGISTICS SERVICES SUBTOTAL | $[+] | ||||
| MEDICAL/SAE MANAGEMENT | UNIT COST | UNITS | MEASURE OF UNIT | TOTAL | |
| 49 | Medical Management | $[+] | 22 | Month | $[+] |
| 50 | Create Safety Plan | $[+] | 1 | Plan | $[+] |
| 51 | Review Protocol Deviation Log | $[+] | 22 | Month | $[+] |
| 52 | Tracking Protocol Waivers | $[+] | 22 | Month | $[+] |
| 53 | Lab Alert/Patient Review | $[+] | 22 | Month | $[+] |
| 54 | Review of AE Data Listings on a Monthly basis | $[+] | 22 | Month | $[+] |
| 55 | Create Safety Database | $[+] | 1 | Database | $[+] |
| 62 | SAE Management | $[+] | 19.0 | SAE | $[+] |
| MEDICAL/SAE MANAGEMENT SERVICES SUBTOTAL | $[+] | ||||
| DATA MANAGEMENT | UNIT COST | UNITS | MEASURE OF UNIT | TOTAL | |
| 56 | Data Entry Activities | $[+] | 56,264 | CRF Pg | $[+] |
| 57 | Generate/Track/Resolve Queries | $[+] | 11253 | Query | $[+] |
| 58 | Data Cleaning/Manual Listing Review | $[+] | 417 | Patient | $[+] |
| 59 | Import Other Data | $[+] | 25 | Transfer | $[+] |
| 60 | Export Data to Sponsor | $[+] | 2 | Transfer | $[+] |
| 61 | Manual Coding | $[+] | 4170 | Manual Code | $[+] |
| 63 | Archive Study Records, Database | $[+] | 1 | Database | $[+] |
| 64 | Data Base Lock Activities - Cohort A | $[+] | 1 | Total | $[+] |
| Data Base Lock Activities - Cohort B | $[+] | 1 | Total | $[+] | |
| DATA MANAGEMENT FEES SUBTOTAL | $[+] |
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 14 |
| Integrium, LLC. | Confidential |
| EDC SYSTEM MAINTAINANCE | UNIT COST | UNITS | MEASURE OF UNIT | TOTAL | |
| 65 | Coding System (Set-up Cost) [WHO/MEDRA] | $[+] | 1 | Access User | $[+] |
| 66 | Third Party Data Integrations | $[+] | 32 | Transfer | $[+] |
| 67 | SAS Platform (months) | $[+] | 30 | Month | $[+] |
| 68 | Help Desk Support | $[+] | 22 | Month | $[+] |
| 69 | Ongoing Support Project Management | $[+] | 15 | Month | $[+] |
| 70 | CRF Export Programming (Site Archives, eCRFs for Submission) | $[+] | 1 | Total | $[+] |
| 71 | Provide End of Study Archives to All Sites and 2 Copies to Sponsor | $[+] | 1.0 | Total | $[+] |
| EDC SYSTEM SET-UP AND MAINTAINANCE SUBTOTAL | $[+] | ||||
| BIOSTATISTICAL ANALYSIS | UNIT COST | UNITS | MEASURE OF UNIT | TOTAL | |
| 72 | Draft & Final Statistical Analysis Plan (SAP) | $[+] | 1 | SAP | $[+] |
| 73 | Analysis DataSets | $[+] | 17 | Dataset | $[+] |
| 74 | Create/Document ADaM (Submission Ready) Datasets | $[+] | 17 | Dataset | $[+] |
| 75 | Statistical Programming Deliverables (TLGs) | $[+] | 191 | T/L/G | $[+] |
| 76 | Generate/QC TLFs | $[+] | 208 | Appendix | $[+] |
| 77 | Output Review/Dry Runs | $[+] | 3 | Dry Run | $[+] |
| 78 | Post-hoc Analysis Hours | $[+] | 120 | Hour | $[+] |
| BIOSTATISTICAL ANALYSIS SUBTOTAL | $[+] | ||||
| MEDICAL WRITING | UNIT COST | UNITS | MEASURE OF UNIT | TOTAL | |
| 79a | Finalize Protocol | $[+] | 1 | Protocol | $[+] |
| 79b | Write Protocol Amendment | $[+] | 3 | Amendment | $[+] |
| 80a | Develop/Finalize ICF | $[+] | 1 | Total | $[+] |
| 80b | Develop/Finalize ICF Amendment | $[+] | 2 | Amendment | $[+] |
| 81 | Final CSR | $[+] | 1 | Total | $[+] |
| MEDICAL WRITNG SUBTOTAL | $[+] | ||||
| CRO SERVICE FEES GRAND TOTAL | $[+] | ||||
| PASS THROUGH COSTS | UNIT COST | UNITS | MEASURE OF UNIT | TOTAL | |
| 1 | Pre-study Site Evaluation Visit | $[+] | 22 | Visit | $[+] |
| 2 | Site Initiation Visit | $[+] | 23 | Visit | $[+] |
| 3a | Interim Monitoring Visits - One Day | $[+] | 350 | Visit | $[+] |
| 3b | Interim Monitoring Visits - Additional Day On-site | $[+] | 100 | Day | $[+] |
| 4 | Close-out Visits | $[+] | 39 | Visit | $[+] |
| 5 | Investigators' Meeting Planner | $[+] | 1 | Meeting | $[+] |
| 6 | Investigator Grants | $[+] | $[+] | ||
| 6a | # Patients Completed | $[+] | 317 | Patient | $[+] |
| 6b | # Screen Failures | $[+] | 273 | Patient | $[+] |
| 6c | # Run-In Failures | $[+] | 57 | Patient | $[+] |
| 6d | # Early Terminations | $[+] | 43 | Patient | $[+] |
| 6e | # Rescue Visits | $[+] | 1 | Visit | $[+] |
| 6f | # Unscheduled visits | $[+] | 1 | Visit | $[+] |
| 7 | Site: Advertising/Patient Recruitment | $[+] | 39 | Site | $[+] |
| 8 | Site: Archive Fees | $[+] | 39 | Site | $[+] |
| 9 | Site: Start-up Costs | $[+] | 39 | Site | $[+] |
| 10 | Site: Estimated Rescue Meds | $[+] | 40 | Site | $[+] |
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 15 |
| Integrium, LLC. | Confidential |
| PASS THROUGH COSTS | UNIT COST | UNITS | MEASURE OF UNIT | TOTAL | |
| 11 | Site: Regulatory Fee | $[+] | 1 | Site | $[+] |
| 12 | Site: Pharmacy Fee | $[+] | 1 | Total | $[+] |
| 13 | Central Laboratory Fees | $[+] | 1.0 | Total | $[+] |
| 14 | IWRS Fees | $[+] | 1 | Total | $[+] |
| 15a | Central IRB - Protocol & Advertising Submission | $[+] | 1 | Protocol | $[+] |
| 15b | Central IRB - Site Submissions | $[+] | 39 | Protocol | $[+] |
| 15 | Central IRB annual renewal | $[+] | 39 | Year | $[+] |
| 15d | Central IRB Amendments | $[+] | 67 | Amendment | $[+] |
| 15e | Central IRB Closeout Fee | $[+] | 39 | Site | $[+] |
| 15f | Central IRB PI Change | $[+] | 1 | Site | $[+] |
| 15g | Central IRB - Site Specific Translations | $[+] | 2 | Translation | $[+] |
| 15h | Central IRB - Advertising Approval | $[+] | 4 | Approval | $[+] |
| 16 | Mixed Meal Tolerance Test Supplies: Ensure | $[+] | 40 | Site | $[+] |
| 17a | EDC Platform Product Usage | $[+] | 25 | Total | $[+] |
| 17b | EDC Coding System Integration Fee [WHO/MEDRA] | $[+] | 1 | Total | $[+] |
| 18 | End of study archive CDs to sites; 2 copies to Sponsor | $[+] | 41 | Total | $[+] |
| 19 | Launch Binders | $[+] | 40 | Binder | $[+] |
| 20 | Regulatory Binders | $[+] | 40 | Binder | $[+] |
| 21 | Copying/ Printing | $[+] | 1 | Total | $[+] |
| 22 | Postal & Shipping Fees | $[+] | 1 | Total | $[+] |
| 23 | Sponsor/Internal - Teleconferences | $[+] | 1 | Total | $[+] |
| PASS-THROUGH COSTS TOTAL | $[+] | ||||
| PROJECT'S OVER-ALL TOTAL COST | $[+] |
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 16 |
| Integrium, LLC. | Confidential |
Exhibit 4
Study Payment Schedule
| Payment Schedule | |||||
| Monthly Management Fees | Month | $ Amount | Verification of Milestone Completion/Deliverables | ||
| Project Management Fees | November 2017 | $[+] | Paid | ||
| Project Management Fees | December 2017 | $[+] | Paid | ||
| Project Management Fees | January 2018 | $[+] | Paid | ||
| Project Management Fees | February 2018 | $[+] | Paid | ||
| Project Management Fees | March 2018 | $[+] | Paid | ||
| Project Management Fees | April 2018 | $[+] | Paid | ||
| Project Management Fees | May 2018 | $[+] | Paid | ||
| Project Management Fees | June 2018 | $[+] | Paid | ||
| Project Management Fees | July 2018 | $[+] | Paid | ||
| Project Management Fees | August 2018 | $[+] | Paid | ||
| Project Management Fees | September 2018 | $[+] | Paid | ||
| Project Management Fees | October 2018 | $[+] | Paid | ||
| Project Management Fees | November 2018 | $[+] | Paid | ||
| Project Management Fees | December 2018 | $[+] | Paid | ||
| Project Management Fees | January 2019 | $[+] | Paid | ||
| Project Management Fees | February 2019 | $[+] | Paid | ||
| Project Management Fees | March 2019 | $[+] | Paid | ||
| Project Management Fees | April 2019 | $[+] | Invoiced Monthly | ||
| Project Management Fees | May 2019 | $[+] | Invoiced Monthly | ||
| Project Management Fees | June 2019 | $[+] | Invoiced Monthly | ||
| Project Management Fees | July 2019 | $[+] | Invoiced Monthly | ||
| Project Management Fees | August 2019 | $[+] | Invoiced Monthly | ||
| Project Management Fees | September 2019 | $[+] | Invoiced Monthly | ||
| Project Management Fees | October 2019 | $[+] | Invoiced Monthly | ||
| Project Management Fees | November 2019 | $[+] | Invoiced Monthly | ||
| Project Management Fees | December 2019 | $[+] | Invoiced Monthly | ||
| Project Management Fees | January 2020 | $[+] | Invoiced Monthly | ||
| Project Management Fees | February 2020 | $[+] | Invoiced Monthly | ||
| Project Management Fees | March 2020 | $[+] | Invoiced Monthly | ||
| Project Management Fees | April 2020 | $[+] | Invoiced Monthly | ||
| Project Management Fees | May 2020 | $[+] | Invoiced Monthly | ||
| Total Monthly Management Fees: | $[+] | ||||
| Monthly Service Fees | Date | % Total Service Budget | % Milestone Service Budget | $ Amount | Verification of Milestone Completion/Deliverables |
| Contract Execution | 12/1/2017 | 4.15% | 10.48% | $[+] | Paid |
| Cohort A: 1st Subject Entered | 4/20/2018 | 2.08% | 4.18% | $[+] | Paid |
| Cohort A: 25% Subjects Randomized | 6/4/2018 | 3.46% | 6.97% | $[+] | Paid |
| Cohort A: 50% Subjects Randomized | 7/19/2018 | 3.46% | 6.97% | $[+] | Paid |
| Cohort A: 75% Subjects Randomized | 9/2/2018 | 3.46% | 6.97% | $[+] | Paid |
| Cohort A: 100% Subjects Randomized | 3/29/2019 | 3.46% | 6.97% | $[+] | Paid |
| Cohort A: 1st Subject Last Visit | 8/22/2018 | 2.08% | 4.18% | $[+] | Paid |
| Cohort A: 25% Subjects Last Visit | 10/15/2018 | 2.08% | 4.18% | $[+] | Paid |
Amendment #1 to Oramed Clinial Research Organization Services Agreement Protocol # ORA-D-015 | 17 |
| Integrium, LLC. | Confidential |
| Cohort A: 50% Subjects Last Visit | 11/29/2018 | 2.08% | 4.18% | $[+] | Paid |
| Cohort A: 75% Subjects Last Visit | 1/13/2019 | 2.08% | 4.18% | $[+] | Billed pending payment |
| Execution of Amendment 1 | 4/18/2019 | 2.08% | 4.18% | $[+] | Upon execution of Amend. #1 |
| Cohort A: 100% Subjects Last Visit | 8/9/2019 | 2.08% | 4.18% | $[+] | Enrollment log |
| Cohort A: Database Lock | 2/18/2020 | 4.15% | 8.37% | $[+] | Database Lock |
| Cohort A: Draft Final TLGs | 3/10/2020 | 1.80% | 3.63% | $[+] | Draft Final TLGs |
| Cohort B: 1st Subject Entered | 5/6/2019 | 0.83% | 1.67% | $[+] | Billed |
| Cohort B: 25% Subjects Randomized | 6/3/2019 | 0.97% | 1.95% | $[+] | Billed |
| Cohort B: 50% Subjects Randomized | 7/1/2019 | 0.97% | 1.95% | $[+] | Billed |
| Cohort B: 75% Subjects Randomized | 7/29/2019 | 0.97% | 1.95% | $[+] | Enrollment log |
| Cohort A: 100% Subjects Randomized | 9/10/2019 | 0.97% | 1.95% | $[+] | Enrollment log |
| Cohort B: 1st Subject Last Visit | 9/16/2019 | 0.97% | 1.95% | $[+] | Billed |
| Cohort B: 25% Subjects Last Visit | 10/4/2019 | 0.97% | 1.95% | $[+] | Enrollment log |
| Cohort B: 50% Subjects Last Visit | 11/1/2019 | 0.97% | 1.95% | $[+] | Enrollment log |
| Cohort B: 75% Subjects Last Visit | 11/29/2019 | 0.97% | 1.95% | $[+] | Enrollment log |
| Cohort B: 100% Subjects Last Visit | 12/17/2019 | 0.97% | 1.95% | $[+] | Enrollment log |
| Cohort B: Database Lock | 2/18/2020 | 1.11% | 2.23% | $[+] | Database Lock |
| Cohort B: Draft Final TLGs | 2/25/2020 | 0.48% | 0.96% | $[+] | Draft Final TLGs |
| Total Milestone Based Services: | 49.59% | 100.00% | $[+] | ||
| Unit Based Payments: Actual Units Invoiced Monthly | % Total Services Budget | # Units | Unit Cost | $ Amount | Verification of Milestone Completion/Deliverables |
| SAE Management | 0.79% | 19 | $[+] | $[+] | Invoiced monthly as occurred |
| Total Unit Based Services: | $[+] | ||||
| Total Services: | $[+] | ||||
| Pass-through expenses | $ Amount | Verification of Milestone Completion/Deliverables | |||
| Monitoring Visit Travel Expenses | $[+] | Invoiced as Actuals Monthly | |||
| Investigator Grants | $[+] | Invoiced and Paid in Advance of Payment to Vendor | |||
| Site Start-up Costs | $[+] | Invoiced and Paid in Advance of Payment to Sites | |||
| Site Advertising | $[+] | Invoiced as Actuals Monthly | |||
| Site Archiving Fees | $[+] | Invoiced as Actuals Monthly | |||
| IRB Fees | $[+] | Invoiced as Actuals Monthly | |||
| Meeting Planner | $[+] | Invoiced and Paid in Advance of Payment to Vendor | |||
| Central Lab Vendor | $[+] | Invoiced and Paid in Advance of Payment to Vendor | |||
| IWRS Vendor | $[+] | Invoiced and Paid in Advance of Payment to Vendor | |||
| EDC Platform Usage Fees | $[+] | Invoiced as Actuals Monthly | |||
| Copying/Printing/Supplies | $[+] | Invoiced as Actuals Monthly | |||
| Postal & Shipping Fees | $[+] | Invoiced as Actuals Monthly | |||
| Sponsor/Internal - Teleconference System | $[+] | Invoiced as Actuals Monthly | |||
| Total Pass-through Budget: | $[+] | ||||
| Grand Total Budget: | $[+] | ||||
Amendment #1 to Oramed Clinial Research Organization Services Agreement
Protocol # ORA-D-015
