What are investigator-initiated clinical trials?

Investigator-initiated clinical trials are clinical studies sponsored and conducted by independent investigators. After the 2003 amendment to the Japanese Pharmaceutical Affairs Law (PAL), pharmaceutical and medical device manufacturers could provide investigational products to clinician investigators to conduct a clinical trial under a Clinical Trial Notification (CTN). In these investigator-initiated clinical trials, the sponsor-investigator is responsible for designing the study and preparing the protocol as well as submitting a CTN to the Pharmaceutical and Medical Devices Agency (PMDA).

Clinical Trial Grant Program

JMACCT supports investigator initiated-clinical trials conducted under a CTN through three grant schemes under the ‘Large Scale Clinical Trial Network Project.’

What kind of clinical trials do we fund?

JMACCT’s support focuses on investigator-initiated clinical trials of new, urgently needed drugs or existing drugs with new indications for which regulatory approval is not being pursued due to a lack of financial incentives.

Specifically, the grant program is designed to accelerate clinical development of medical products that are:

• Widely used as standard treatment in the US or EU but not yet approved in Japan.
• Already marketed in Japan and commonly used for off-label indications.

Through funding investigator-initiated clinical trials, JMACCT contributes to delivering those critically needed drugs to patients who will benefit from them. For a list of awarded researches, click here.

JMACCT’s Grant Schemes

If awarded, an investigator-initiated clinical trial will be funded in stages, through three grant schemes:

• Clinical Trial Planning Grant
• Clinical Trial Coordination/Management Grant
• Clinical Trial Implementation Grant

Scope

• Clinical Trial Planning Grant
  This grant is designed to provide support for the finalization of the trial protocol and the preparation of other essential documents including the Investigator’s Brochure, Case Report Form and Informed Consent Form.
• Clinical Trial Coordination/Management Grant
  This grant is designed to provide support for establishing a research team and making other necessary arrangements for the conduct of the clinical trial. Such arrangements include selecting Coordinating Investigators and clinical sites from medical institutions registered with MNCT.
• Clinical Trial Implementation Grant
  This grant is designed to provide support for the trial implementation. The clinical sites selected from the MNCT member institutions will execute the trial.

  Calls for Research Proposals

  JMACCT announces calls for research proposals by presenting a list of high priority drugs and medical devices recommended by the member societies of the Japanese Association of Medical Sciences (JAMS).
  The JAMS member societies make recommendations based on the following criteria:

  • A new product or an existing product with new indications that is in the specialized therapeutic areas of a JAMS member society.
  • Prompt regulatory approval of the new product or a new indication of the product is considered desirable so that it becomes available to Japanese patients for appropriate use.
  • In principle, physical, chemical, pharmaceutical, toxicological and pharmacological studies that are relevant to the stage of clinical development of the drug or the medical device must be completed or near completion, as per the Standards for the Implementation of Clinical Trials on Pharmaceutical Products (MHW Ordinance No. 28), the Japanese GCP.
  For a list of current Calls for Proposals, click here. (Available in Japanese only.)

  External Review

  All research proposals for the Clinical Trials Grant Program are assessed by external review body: Research Evaluation Committee. The Committee meets three times a year, typically in March, July and November. Based on input from the Committee, JMACCT decides which proposals are to be funded.

  Insurance for Investigator-Initiated Clinical Trials

  In an investigator-initiated clinical trial, the sponsor-investigator is held responsible for ensuring that adequate insurance and other necessary arrangements are in place as required by GCP.

  JMACCT, in cooperation with an insurance company, developed a new insurance package for the investigator-initiated clinical trials conducted under the Large Scale Clinical Trial Network Project to provide compensation to study participants in the chance that any negative side effects are incurred as a result of study participation.

  The investigators of all clinical trials funded through the JMACCT’s grant scheme are to be included in JMACCT’s insurance policy before the commencement of clinical trials. The insurance costs will be borne by JMACCT.

  JMACCT-funded Research Topics

  The following are the research topics awarded under JMACCT's Grant Program.
  
  

  FY2010 (April 2010-March 2011)

  Investigational Product	Indication	Progress
  lapatinib / trastuzumab	breast cancer	Trial protocol under development
  glucarpidase	conditions treated with high-dose methotrexate	Trial protocol under development
  rituximab	idiopathic thrombocytopenic purpura	Trial protocol under development

  
  
  

  FY2009 (April 2009-March 2010)

  Investigational Product	Indication	Progress
  thalidomide	Crow-Fukase syndrome	CTN submitted

  
  
  

  FY2008 (April 2008-March 2009)

  Investigational Product	Indication	Progress
  self-expanding intracranial stent system	intracranial atherosclerotic disease	CTN submitted

  
  
  

  FY2007 (April 2007-March 2008)

  Investigational Product	Indication	Progress
  rituximab	childhood refractory nephrotic syndrome	CTN submitted
  diode laser for PDT and talaporfin sodium	malignant brain tumor	CTN submitted
  H5N1 influenza vaccine	H5N1 influenza in the pediatric population	Notification of Amendment to Clinical Trial Protocol submitted
  talc	malignant pleural effusions	Notification of Clinical Trial Completion submitted

  
  
  

  FY2005 (April 2005-March 2006)

  Investigational Product	Indication	Progress
  tegafur, gimeracil and oteracil potassium	esophageal neoplasm	CTN submitted
  H5N1 influenza vaccine	H5N1 influenza	Approved on 19 October 2007
  arginine	MELAS*	CTN submitted
  imatinib mesylate and hydroxyurea	adult glioblastoma	Study withdrawn**
  *: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes **: The results of a recently completed overseas clinical trial of similar design revealed insufficient efficacy of the study drug. This made it impossible to pursue approval of the study drug in Japan, and therefore, this research project was withdrawn.

  
  
  

  FY2004 (April 2004-March 2005)

  Investigational Product	Indication	Progress
  irinotecan hydrochloride	refractory pediatric solid tumor	Notification of Clinical Trial Completion submitted
  phenobarbital sodium IV	neonatal convulsions	Approved on 16 October 2008
  bepridil hydrochloride hydrate	persistent atrial fibrillation	Approved on 16 October 2008
  tacrolimus hydrate	interstitial pneumonitis associated with polymyositis / dermatomyositis	CTN submitted
  leuprorelin acetate	spinal and bulbar muscular atrophy (SBMA)	CTN submitted

  
  
  

  FY2003 (April 2003-March 2004)

  Investigational Product	Indication	Progress
  imatinib mesylate	Sarcoma with c-kit (CD117) or PDGFR expression as determined by immunohistochemical staining	Study terminated*
  fentanyl citrate	Adjunct to general anesthesia in neonates and children	Approved on 23 August 2007
  argatroban	Heparin-induced thrombocytopenia (HIT)	Approved on 16 July 2008
  *: The preliminary results from 25 patients participated in this study showed insufficient efficacy (preliminary response rate = 5.6%: 1 of 18 evaluable patients achieved PR as of September 2006). Consequently, the study was closed for further accrual in October 2006 and notification of clinical trial discontinuation was submitted to PMDA in March 2007.

  Achievements

  Some of the investigator-initiated clinical trials conducted under JMACCT’s Grant Program have already led to approval of a new vaccine and new indications of existing drugs.

   

  Investigational Product	Indication	Approval Date
  fentanyl citrate	Adjunct to general anesthesia in neonates and children	23 August 2007
  H5N1 influenza vaccine	H5N1 influenza	19 October 2007

   

  For a summary of the progress of each clinical research project, click here. (Available in Japanese only.)