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Exhibit 10.12.3    
    


AMENDEMENT No. 2 TO CLINICAL TRIAL AGREEMENT  


        This AMENDMENT NO. 2 TO CLINICAL TRIAL AGREEMENT (the "Amendment 2") is made and entered into as of the 28th day of January, 2004, by and between  Gentium
S.p.A. (formerly Crinos Industria Farmacobiologica S.p.A.) a corporation having an office at Piazza XX Settembre 2, 22079 Villa Guradia, Como
Italy (the "Company") and Dana-Farber/Partners Cancer Care, Inc., a non-profit corporation having an office at 44 Binney Street,
Boston, Massachusetts, 02115, USA ("DFPCC"). 


        WHEREAS,
the Company and DFPCC entered into a Clinical Trial Agreement dated December 27, 1999 (the "Clinical Trial Agreement") and an Amendment No. 1 to Clinical Agreement
in October 2000 (the "Amendment"), which relates to the conduct of a clinical study of Defibrotide in accordance with the study protocol entitled "Defibrotide for Hematopoietic Stem Cell
Transplant (SCT) Patients with Severe Hepatic Veno-Occlusive Disease (VOD): A Randomized Phase I/II Study to Determine the Effective Dose;" and 


        WHEREAS,
the parties desire to expand the number of subjects participating in the Study. 


        NOW,
THEREFORE, in consideration of the mutual agreements, promises and covenants provided herein, the Company and DFPCC hereby agree to amend the Clinical Trial Agreement as follows: 



Section 1: Budget  


        With reference to Section 4: Budget of the Clinical Trial Agreement, this section is hereby amended to
include an additional Two hundred thousand U.S. Dollars ($200,000) and restated in its entirety to read as follows: 




Company
agrees to support this Study with a research grant of Four hundred fifty thousand U.S. Dollars ($450,000) inclusive of indirect costs. The agreed upon budget is attached hereto as
Exhibit B. 














        IN
WITNESS WHEREOF, THE COMPANY AND DFPCC have by their own hands or by their respective officers executed the Amendment No. 2 to Clinical Trial Agreement effective as of the date
first set forth above. 



	THE COMPANY:

CRINOS INDUSTRIA

FARMACOBIOLOGICA S.P.A.	 	DFPCC:

DANA-FARBER/PARTNERS CANCER

CARE, INC.
	

GENTIUM S.P.A.	
 	

 	

 
	

BY:	

/s/  Laura Iris Ferro      
	
 	

BY:	

/s/  Willam M. Corbett, Jr.      

	

TITLE:	

PRESIDENT
	
 	

TITLE:	

WILLIAM M. CORBETT, JR.

DIRECTOR OF RESEARCH ADMINISTRATION

	

DATE:	

March 19, 2004
	
 	

DATE:	

2/9/04

	

 	

 	
 	

 	

 





        I
have read the foregoing Amendment No. 2 and agree to comply with the obligations of Investigators stated therein. 



	

/s/  Paul Richardson      
 Paul Richardson, M.D.	
 	

 
	

 	
 	

 	
 	

 
	

DATE:	
 	

    
	
 	

 









        "Diferotide
for Hematopoietic Stem Cell Transplant (STC) Patients with Severe Hepatic Veno-Occlusive Disease

(VOA): A Phase I/II Study to Determine Minimal Effective Dose" 



	Protocol No

Duration of Study (months)

Number of Patients
	 	99-118

12

20

(total of 80pts)
	 	Company Name

Overall Site

Overall P.I.

Site P.I.
	 	CRINOS

DFCI

RICHARDSON, MD

	BUDGET ITEMS
	 	Percent Effort
	 	Study Total
	 	Amount Per Patient

	PERSONNEL:	 	 	 	 	 	 	 	 
	Site Principal Investigator	 	11%	 	$	16,512	 	$	826
	Project Manager	 	45%	 	$	25,775	 	$	1,289
	Data Manager (Parisa Momtaz)	 	100%	 	$	38,272	 	$	1,914
	Research Nurse	 	0%	 	$	0	 	$	0
	 	 	
	 	
	 	

	 	Total Salaries	 	 	 	$	80,559	 	$	4,028
	Employee Benefits    M.D.	 	29.00%	 	$	4,789	 	$	239
	Employee Benefits    Non-M.D.	 	26.00%	 	$	16,652	 	$	833
	 	 	
	 	
	 	

	 	Total Benefits	 	 	 	$	21,441	 	$	1,072
	 	 	
	 	
	 	

	TOTAL PERSONNEL	 	 	 	$	102,000	 	$	5,100
	 	 	
	 	
	 	

	
OUTPATIENT CARE COSTS	
 	

 	
 	
 	

 	
 	
 	

 
	Tests/Procedures, etc.	 	 	 	$	0	 	$	0
	 	Subtotal Outpatient Care	 	 	 	$	0	 	$	0
	INPATIENT CARE COSTS	 	 	 	 	 	 	 	 
	Bed Day Rates	 	None	 	 	 	 	 	 
	Other Procedures	 	 	 	$	0	 	$	0
	 	Subtotal Inpatient Care	 	 	 	$	0	 	$	0
	
PHARMACY: Prep, Storage, etc.	
 	

Pharmacy Charge Form	
 	
$	

0	
 	
$	

0
	 	 	
	 	
	 	

	TOTAL PATIENT CARE	 	 	 	$	0	 	$	0
	 	 	
	 	
	 	

	Pharmacokinetics	 	DFCI/MGH/Other

ý  ý  ý	 	$	50,000	 	$	2,500
	 	 	
	 	
	 	

	TOTAL PHARMACOKINETICS*	 	 	 	$	50,000	 	$	2,500
	 	 	
	 	
	 	

	*Includes set-up charge of $15,000 at Childrens Hospital
	
OTHER EXPENSES	
 	

 	
 	
 	

 	
 	
 	

 
	Supplies	 	 	 	$	1,000	 	$	50
	Shipping Costs	 	 	 	$	0	 	$	0
	Travel (Protocol or Scient. Mtgs)	 	 	 	$	2,500	 	$	125
	Equipment	 	 	 	$	0	 	$	0
	Shared Resources (eg, MDLab)	 	 	 	$	0	 	$	0
	Storage Fees	 	 	 	$	0	 	$	0
	CER Lab	 	 	 	$	4,500	 	$	225
	 	 	
	 	
	 	

	TOTAL OTHER EXPENSES	 	 	 	$	8,000	 	$	400
	 	 	
	 	
	 	

	TOTAL DIRECT COSTS:	 	 	 	$	160,000	 	$	8,000
	 	 	
	 	
	 	

	Indirect Costs @ 25% Total Direct Costs	 	 	 	$	40,000	 	$	2,000
	 	 	
	 	
	 	

	TOTAL COSTS PER PATIENT**	 	 	 	$	200,000	 	$	10,000
	 	 	
	 	
	 	

	
Protocol Review and Renewals	
 	

 	
 	
$	

0	
 	
 	

 
	 	 	
	 	
	 	

	Start-Up Costs	 	 	 	$	0	 	 	 
	 	 	
	 	
	 	

	TOTAL STUDY COSTS**	 	 	 	$	200,000	 	 	 
	 	 	
	 	
	 	








**Includes
payments to sub-contract sites 











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Exhibit 10.12.3