Efficacy of Eltrombopag to Improve Thrombocytopenia of MYH9-related Disease

Condition(s) targeted: Blood Platelet Disorders

Intervention: eltrombopag (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: IRCCS Policlinico S. Matteo

Official(s) and/or principal investigator(s):
Carlo Balduini, MD, Principal Investigator, Affiliation: IRCCS Policlinico San Matteo Foundation, Pavia, Italy

Overall contact:
Carlo Balduini, MD, Phone: 00390382502183, Email: c.balduini@smatteo.pv.it

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.

Official title: An Exploratory Phase II Dose Escalation Study of Eltrombopag in MYH9 Related Disease

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: platelet count determined by phase-contrast microscopy

Secondary outcome:

bleeding tendency assessed by WHO bleeding score

all types of adverse events

in vitro function of platelets produced during therapy in responding patients

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

- Any other disease or condition that by the advise of the responsible physician would

make the treatment dangerous for the patient or would make the patient ineligible for the study, including physical, psychiatric, social and behavioral problems. HCV positivity and liver diseases will not be considered an exclusion criterion since a phase II study showed that eltrombopag was effective and safe in this patient population.

Carlo Balduini, MD, Phone: 00390382502183, Email: c.balduini@smatteo.pv.it

Azienda Ospedaliero-Universitaria di Padova, Unità di Medicina Generale e Patologia Speciale, Padova 35128, Italy; Recruiting
Fabrizio Fabris, MD, Email: fabrizio.fabris@unipd.it
Fabrizio Fabris, MD, Principal Investigator

Fondazione IRCCS Policlinico San Matteo, Unità di Medicina III, Pavia 27100, Italy; Recruiting
Carlo Balduini, MD, Phone: 00390382502183, Email: c.balduini@smatteo.pv.it
Alessandro Pecci, MD, PhD, Phone: 00390382501385, Email: alessandro.pecci@unipv.it
Carlo Balduini, MD, Principal Investigator
Alessandro Pecci, MD, PhD, Sub-Investigator
Patrizia Noris, MD, PhD, Sub-Investigator

Policlinico Monteluce, Sezione di Medicina Interna e Cardiovascolare, Perugia 06122, Italy; Recruiting
Paolo Gresele, MD, PhD, Email: grespa@unipg.it
Paolo Gresele, MD, PhD, Principal Investigator

Italian National Monitoring Centre for Clinical Trials

European Clinical Trial Database Home Page

Related publications:

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.

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. Epub 2001 Dec 14.

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.

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.

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.

Starting date: January 2009
Last updated: May 28, 2010