Efficacy of Eltrombopag to Improve Thrombocytopenia of MYH9-related Disease

NCT01133860 | Completed Phase 2 Results DMC

• 1 other identifier: Eltrombopag-MYH9-2008
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

The term MYH9-related disease (MYH9RD) includes four genetic disorders: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome. All these disorders derive from mutation of a unique gene, named MYH9, and they have been recognized as different clinical presentations of a single illness that was named MYH9RD. All patients affected by MYH9RD present since birth with thrombocytopenia, which can result in a variable degree of bleeding diathesis; some of them subsequently develop additional clinical manifestations, such as renal damage, sensorineural hearing loss, and/or presenile cataracts. Eltrombopag is an oral thrombopoietin receptor agonist that stimulates proliferation and differentiation of megakaryocytes, the bone marrow cells that produce blood platelets. This drug is effective in increasing platelet count in healthy volunteers, as well as in patients affected by some acquired thrombocytopenias, such as idiopathic thrombocytopenic purpura and HCV related thrombocytopenia. The purpose of this study is to determine if eltrombopag, administered orally at the dose of 50 or 75 mg/daily for up to 6 weeks, is effective in increasing platelet count of patients affected by MYH9RD. Further aims of this study are to test if eltrombopag is effective in reducing bleeding tendency of MYH9RD patients; to evaluate safety and tolerability of eltrombopag in patients with MYH9RD; to evaluate in vitro function of platelets produced during therapy in patients responding to this drug.

Conditions

Blood Platelet Disorders

Keywords

inherited thrombocytopenia; MYH9 mutations; eltrombopag

Outcome Measures

Primary Outcomes (1)

• Response to Drug Based on Platelet Count at the End of Therapy

  The primary endpoints were the achievement of a platelet count over 100 x10e9/L or at least 3 times the baseline value (major response), or at least twice the baseline value but less than major response (minor response). The overall response to therapy is reported. Platelet count was measured at the end of therapy (21 or 42 days, see study design) by phase-contrast microscopy.

  21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy

Secondary Outcomes (3)

• Bleeding Tendency Assessed by WHO Bleeding Score

  21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy

• All Types of Adverse Events

  21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy

• in Vitro Function of Platelets Produced During Therapy in Responding Patients

  21 days or 42 days of therapy

Study Arms (1)

eltrombopag

EXPERIMENTAL

Drug: eltrombopag

Interventions

eltrombopag DRUG

Eltrombopag, administered orally, 50 mg/daily for 21 days. Patients with platelet counts between 100 and 150x10e9/L at day 21 will continue eltrombopag 50 mg/daily for 21 additional days. Patients with platelet count lower than 100x10e9/L at day 21 will receive eltrombopag 75 mg/daily for additional 21 days. Patients with more than 150x10e9 platelets/L at day 21 will stop therapy.

Also known as: Revolade, Promacta

eltrombopag

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 16 years or more
• Confirmed diagnosis of MYH9-related disease
• Average platelet count for the previous year less than 50x10e9/L
• Written informed consent

You may not qualify if:

• Diseases known to involve the risk of thromboembolic events (e.g. atrial fibrillation)
• History of thrombosis within 1 year
• Use of drugs that affect platelet function (including but not limited to, aspirin, clopidogrel or NSAIDS) or anti-coagulants
• Females who are pregnant or nursing (a negative pregnancy test in required before enrollment of fertile women)
• Formal refusal of any recommendation of a safe contraception
• Alcohol or drug addiction
• Altered renal function as defined by creatinine of 20 mg/L or more

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead
• University of Pavia: collaborator
• GlaxoSmithKline: collaborator
• Azienda Ospedaliera di Padova: collaborator
• Azienda Ospedaliera di Perugia: collaborator
• Fondazione Telethon: collaborator

Study Sites (3)

Azienda Ospedaliero-Universitaria di Padova, Unità di Medicina Generale e Patologia Speciale

Padua, 35128, Italy

Location

Fondazione IRCCS Policlinico San Matteo, Unità di Medicina III

Pavia, 27100, Italy

Location

Policlinico Monteluce, Sezione di Medicina Interna e Cardiovascolare

Perugia, 06122, Italy

Location

Related Publications (6)

• Seri M, Cusano R, Gangarossa S, Caridi G, Bordo D, Lo Nigro C, Ghiggeri GM, Ravazzolo R, Savino M, Del Vecchio M, d'Apolito M, Iolascon A, Zelante LL, Savoia A, Balduini CL, Noris P, Magrini U, Belletti S, Heath KE, Babcock M, Glucksman MJ, Aliprandis E, Bizzaro N, Desnick RJ, Martignetti JA. Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium. Nat Genet. 2000 Sep;26(1):103-5. doi: 10.1038/79063.

  PMID: 10973259 BACKGROUND

• Seri M, Savino M, Bordo D, Cusano R, Rocca B, Meloni I, Di Bari F, Koivisto PA, Bolognesi M, Ghiggeri GM, Landolfi R, Balduini CL, Zelante L, Ravazzolo R, Renieri A, Savoia A. Epstein syndrome: another renal disorder with mutations in the nonmuscle myosin heavy chain 9 gene. Hum Genet. 2002 Feb;110(2):182-6. doi: 10.1007/s00439-001-0659-1. Epub 2001 Dec 14.

  PMID: 11935325 BACKGROUND

• Seri M, Pecci A, Di Bari F, Cusano R, Savino M, Panza E, Nigro A, Noris P, Gangarossa S, Rocca B, Gresele P, Bizzaro N, Malatesta P, Koivisto PA, Longo I, Musso R, Pecoraro C, Iolascon A, Magrini U, Rodriguez Soriano J, Renieri A, Ghiggeri GM, Ravazzolo R, Balduini CL, Savoia A. MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore). 2003 May;82(3):203-15. doi: 10.1097/01.md.0000076006.64510.5c.

  PMID: 12792306 BACKGROUND

• Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, Kloczko J, Hassani H, Mayer B, Stone NL, Arning M, Provan D, Jenkins JM. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007 Nov 29;357(22):2237-47. doi: 10.1056/NEJMoa073275.

  PMID: 18046028 BACKGROUND

• McHutchison JG, Dusheiko G, Shiffman ML, Rodriguez-Torres M, Sigal S, Bourliere M, Berg T, Gordon SC, Campbell FM, Theodore D, Blackman N, Jenkins J, Afdhal NH; TPL102357 Study Group. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med. 2007 Nov 29;357(22):2227-36. doi: 10.1056/NEJMoa073255.

  PMID: 18046027 BACKGROUND

• Pecci A, Gresele P, Klersy C, Savoia A, Noris P, Fierro T, Bozzi V, Mezzasoma AM, Melazzini F, Balduini CL. Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations. Blood. 2010 Dec 23;116(26):5832-7. doi: 10.1182/blood-2010-08-304725. Epub 2010 Sep 15.

  PMID: 20844233 DERIVED

MeSH Terms

Conditions

Blood Platelet Disorders

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Prof. Carlo Balduini
• Organization: IRCCS Policlinico San Matteo Foundation

c.balduini@smatteo.pv.it

0039.0382.502580

Study Officials

• Carlo Balduini, MD

  IRCCS Policlinico San Matteo Foundation, Pavia, Italy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 28, 2010
• First Posted: May 31, 2010
• Study Start: January 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: July 26, 2011
• Results First Posted: July 21, 2011

Record last verified: 2010-07

Locations

IT (3)