Exhibit 4.12



Changed Order 4.1 to Clinical Services Agreement



Sponsor’s study drug RHB-104



This CO#4.1 to the Clinical Services Agreement signed 15 June 2011
(“Clinical Services Agreement”), is by and among:



(1) RedHill Biopharma Ltd., having its principle place of business
at 21 Ha’arba’a St., Tel Aviv 64739, Israel (hereafter “SPONSOR”);



(2) 7810962 Canada Inc., a Canadian corporation, having its
principal office at 245 Victoria Ave, Suite 100, Montreal, Quebec, H3Z 2M6, Canada (hereinafter "MANAGER");



WHEREAS, “SPONSOR” mandated "MANAGER" to enter
into a subcontract with inVentiv Health Clinical to act as a CRO for its Study (as defined in the Clinical Services Agreement)
with an expected termination date of March 2013; however, the study as of the Amendment Effective Date is ongoing;



WHEREAS, FURTHER as due to the initial term of the Clinical Services
Agreement being only 2 years, the parties have omitted from the calculation of professional fees an applicable annual inflation
rate therein;



WHEREAS, FURTHER the parties now wish to include inflation to account
for the extended term;



WHEREAS, FURTHER PharmaNet GmbH has assigned all of their rights,
title and interest in and to the Agreement as of 1 July 2014 to inVentiv Health UK as part of an internal reorganization; and



NOW THEREFORE, in exchange of mutual consideration the sufficiency
of which is hereby acknowledged, the parties hereto agree to the following amendment(s) to the Agreement:



| | 1. | As of 1 January 2015 an inflation rate of 2% per year will be included in the calculation of the
professional fees agreed upon in the Clinical Services Agreement.
| | -- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------



| | 2. | Except as amended herein, the Clinical Services Agreement remains
in full force and effect.
| | -- | -------------------------------------------------------------------------------------------















IN WITNESS WHEREOF, this change Order 4.1 has been executed by the parties hereto through
their duly authorized officers and is effective as the last date below.





ACCEPTED AND AGREED TO:





|RedHill Biopharma Ltd.          | For 7810962 Canada Inc. |                              
|------------------------------- | ----------------------- | -----------------------------
|                                |                         |                              
|                                |                         |                              
|/s/ Ori Shilo                   |                         |                              
|Name: Ori Shilo                 |                         |                              
|Title: Deputy CEO               |                         | /s/ Alain Guimond            
|                                |                         | Name:  Alain Guimond PhD     
|                                |                         | Title: Senior Director of R&D
|Date: August 9, 2015            |                         | Date: 06Aug2015              
|                                |                         |                              
|                                |                         |                              
|RedHill Biopharma Ltd.          |                         |                              
|                                |                         |                              
|/s/ Uri Hananel Aharon          |                         |                              
|Name: Uri Hananel Aharon        |                         |                              
|Title: Chief Accounting Officer |                         |                              
|                                |                         |                              
|                                |                         |                              
|Date: August 9, 2015            |                         |