Clinical Trials Resource Center

Thrombocytopenia and Thrombocytopenia Prevention

October 2, 2017

Shionogi issued results of a phase III study of lusutrombopag (S-888711) for thrombocytopenia in patients with chronic liver disease undergoing non-emergent invasive procedures. L-PLUS2 was a multi-national, double-blind, placebo-controlled study. A total of 215 patients were randomized 1:1 to receive 3mg of lusutrombopag, or placebo, up to seven days. Top-line L-PLUS2 study results include: 64.8% of lusutrombopag patients versus 29% of placebo patients met the primary efficacy endpoint; 64.8% of patients taking lusutrombopag achieved a platelet count of at least 50,000/µL and had an increase in platelet count of at least 20,000/µL from baseline, compared to 13.1% of patients taking placebo; and Lusutrombopag was generally well-tolerated. Based on the results from the L-PLUS1 and L-PLUS2 phase III studies, Shionogi has initiated rolling submission of a New Drug Application to the FDA.

October 31, 2016

Rigel Pharmaceuticals has announced results for the second of two double-blind studies in the FIT phase III clinical program for fostamatinib in adult chronic/persistent immune thrombocytopenia (ITP). The FIT program consists of two identical multicenter, randomized, double-blind, placebo-controlled studies of approximately 75 adult patients each. The patients had been diagnosed with persistent or chronic ITP, have failed at least one prior therapy for ITP, and have platelet counts consistently below 30,000/uL of blood. Patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo orally twice a day for up to 24 weeks. The primary efficacy endpoint of this program is a stable platelet response defined as achieving platelet counts greater than 50,000/uL of blood for at least four of the six scheduled clinic visits between weeks 14 and 24 of treatment. The primary endpoint in the study was a stable platelet response, defined as platelet counts greater than 50,000/uL of blood on at least four of the last six scheduled clinic visits between weeks 14 and 24 of treatment. In the FIT 2 (Study 048) phase III study, the fostamatinib response rate was 18%, consistent with the recently reported FIT 1 (Study 047) phase III study. In Study 048, one patient in the placebo group (4%) achieved a stable platelet response; therefore the difference between those on treatment and those on placebo did not reach statistical significance (p=0.152) and the study did not meet its primary endpoint. When the data from both studies are combined, however, this difference is statistically significant (p=0.007). Data from both FIT phase III studies and the open-label extension study demonstrates the consistent benefit of fostamatinib in ITP.

September 12, 2016

Rigel Pharmaceuticals issued results of a phase III study of fostamatinib for adult chronic/persistent immune thrombocytopenia (ITP). The FIT program consisted of two identical multicenter, randomized, double-blind, placebo-controlled studies of approximately 75 adult patients each. The patients have been diagnosed with persistent or chronic ITP, and have blood platelet counts consistently below 30,000/uL of blood. The patients all had experience with at least one other ITP treatment such as steroids, Rituxan, splenectomy and/or TPO mimetics. Patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo twice a day to be taken for up to six months. Study subjects remained on treatment for up to 24 weeks. The primary efficacy endpoint of this program is a stable platelet response defined as achieving platelet counts at or above 50,000/uL of blood for at least four of the last six clinic visits of the study. Patients were subsequently offered to enroll in an open-label, phase III, long-term extension study, which is ongoing. The study (n=76) showed that 18% of patients receiving fostamatinib achieved a stable platelet response compared to none receiving a placebo control (p=0.0261). A stable platelet response was defined as achieving greater than 50,000 platelets per uL of blood on at least four of the last six scheduled visits between weeks 14 and 24 of treatment. The most frequent adverse events were gastrointestinal-related, and the safety profile of the product was consistent with prior clinical experience, and no new or unusual safety issues were discovered. If these results are reproduced in the second phase III study and are supported by the results of a planned interim analysis of the phase III extension study, the company expects to submit a New Drug Application with the FDA in the first quarter of 2017.

May 2, 2016

Amgen issued results of a phase III, randomized, double-blind, placebo-controlled study of Nplate (romiplostim) in children with symptomatic immune thrombocytopenia (ITP). The study enrolled 62 children who had ITP for more than six months to weekly Nplate or placebo (2:1) for 24 weeks. By the final eight weeks of the study, noncutaneous bleeding had decreased with Nplate, and rates of durable platelet response were 52% compared to 10% with placebo (p=0.002, odds ratio 9.1, 95% CI: 1.9, 43.2). Rates of overall platelet response with Nplate were 71% (30/42) compared with 20% with placebo (p=0.0002, odds ratio 9, 95% CI: 2.5, 32.3), and rates of any platelet response were 81% (34/42) with Nplate compared to 55% (11/20) with placebo (p=0.0313). The overall safety profile on the pediatric subjects who received Nplate in this study was similar to the known safety profile of Nplate. The most frequently reported AEs included contusion, epistaxis, headache and upper respiratory tract infections. Oropharyngeal pain occurred more frequently with Nplate [26.2% (11/42) v. 5.3% (1/19) in placebo-treated patients]; of the 11 patients treated with Nplate with oropharyngeal pain, streptococcal pharyngitis (n=2), allergic rhinitis (n=2), gastroesophageal reflux (n=1) and serum sickness from IVIg (n=1) were also reported. No oropharyngeal pain AEs were serious or considered treatment-related. No patients died and none withdrew due to AEs. Serious adverse events (SAEs) were seen in 23.8% of Nplate patients and 5.3% of placebo patients. SAEs seen in the Nplate arm included epistaxis, contusion and headache (n=2 each), bronchiolitis, nausea, petechiae, epilepsy, fever, thrombocytosis, urinary tract infection and vomiting (n=1 each). One subject with treatment-related SAEs experienced headache and thrombocytosis, which did not recur when romiplostim was restarted. There were no thrombotic events reported in the study. The company plans to work with regulatory authorities while seeking approval for Nplate for pediatric patients.

June 25, 2012

CytoPharm and Amarillo Biosciences reported results from a phase II trial of interferon-alpha lozenges for the treatment of thrombocytopenia in patients with hepatitis C virus. This randomized, dose-ranging study enrolled 169 patients in viral remission who had just completed at least 24 weeks of treatment with injectable interferon-alpha (IFNa) and Ribavirin. Subjects received oral lozenges containing 500 or 1500 international units (IU) of natural human IFNa or matching placebo for 24 weeks, followed by 24 weeks of untreated observation. At completion of the study, 81% of subjects who received 500IU lozenges normalized their mean platelet count versus only 42% in the placebo group. In the 40% of subjects who had mild liver fibrosis, only 12% of the 500IU arm experienced virological relapse by the end of the study, compared to 32% in the placebo group—a 63% reduction in relapse rate. The drug was well tolerated. Phase III studies are currently underway.

February 20, 2012

SuppreMol released interim results from a phase Ib/IIa trial of SM101 for Primary Immune Thrombocytopenia (ITP). The phase Ib portion of the trial enrolled 36 subjects who received up to 12 mg/kg intravenous doses of SM101 weekly for four weeks or matching placebo. SM101 was safe and well tolerated and no dose limiting toxicities were reported. There was a dose dependent platelet increase and in the highest dosage group the increase of platelet level continued throughout the three month follow up period. No ITP rescue treatment was necessary.

March 15, 2010

Bristol Myers Squibb and Pfizer reported positive results from a phase III trial of apixaban for the prevention and treatment of venous thromboembolism. This head-to-head, randomized, double-blind, safety and efficacy study, dubbed ADVANCE-2, enrolled 3,221 subjects undergoing elective knee replacement surgery. The subjects received 2.5 mg of apixaban orally twice daily or subcutaneous enoxaparin 40 mg once daily, over a 10-to-14 day treatment period. The primary efficacy endpoint was the composite of asymptomatic and symptomatic deep vein thrombosis, non-fatal pulmonary embolism, and death from any cause during study treatment. The primary efficacy endpoint occurred in 15.1% of the apixaban group and 24.4% of the enoxaparin group, resulting in a statistically significant relative risk reduction for apixaban of 38% (p<0.0001). The secondary efficacy endpoint, major venous thromboembolism, occurred in 1.1% of the apixaban group compared with 2.2% of the enoxaparin group (one-sided p≡0.02). The incidences of major bleeding and clinically relevant non-major bleeding were similar between the treatment arms. All other safety parameters were comparable.

December 14, 2009

Boehringer Ingelheim reported positive results from a phase III trial of dabigatran etexilate for the treatment of secondary venous thromboembolism (VTE). This randomized, double-blind, controlled study, dubbed RE-COVER, enrolled 2,539 subjects with acute VTE. The subjects received 150 mg dabigatran etexilate orally, twice daily or an approved regimen of warfarin for six months. The primary composite endpoint was incidence of recurrent symptomatic VTE and deaths related to VTE during the treatment period. Dabigatran etexilate met the primary outcome of the trial and was non-inferior to dose-adjusted warfarin (2.4% versus 2.1%). In addition, dabigatran etexilate demonstrated a significant 37% reduction in major or clinically relevant non-major bleeding (p≡0.002). Major bleeding was comparable between dabigatran etexilate and warfarin. For any bleeds, dabigatran etexilate showed a significant 29% reduction compared to warfarin (p≡0.0002). These results were achieved without any evidence of liver toxicity.

December 3, 2007

GlaxoSmithKline reported positive results from two phase II trials of Promacta for the treatment of chronic hepatitis C-associated thrombocytopenia and chronic Idiopathic thrombocytopenic purpura (ITP). The first study was an international, multicenter, double-blind, randomized, placebo-controlled, dose-ranging study. A total of seventy-four HCV-infected subjects with platelet counts between 20,000 and 70,000/mL were enrolled. The subjects received Promacta (30mg, 50mg, or 75mg daily) or placebo for four weeks (pre-antiviral phase). The primary endpoint was platelet count increase to greater than or equal to 100,000/mL at week four. The subjects could then initiate antiviral therapy and continue Promacta or placebo for 12 additional weeks (antiviral phase). The primary endpoint was reached by 75%, 79% and 95% of subjects in the Promacta 30mg, 50mg and 75 mg groups respectively, compared to no platelet elevations in the placebo group (p<0.001). Treatment was generally well tolerated, with all adverse events mild to moderate in nature. The second trial was a multicenter, randomized, double-blind, placebo-controlled study. A total of 118 subjects with chronic ITP and platelet counts <30,000/mL and who had relapsed or were refractory to at least one ITP treatment were enrolled. The subjects received once-daily oral Promacta (30mg, 50mg, or 75 mg) or placebo. The primary endpoint was the proportion of subjects with a platelet count greater than or equal to 50,000 per cubic millimeter after up to six weeks of therapy. The primary endpoint was achieved in 28%, 70% and 81% of subjects who received Promacta (30mg, 50mg and 75mg, respectively) compared to 11% of the placebo group <0.001). Platelet counts rose to greater than 200,000/L in 4% of the placebo-treated subjects and in 14%, 37% and 50% of the Promacta 30mg, 50mg and 75mg-treated subjects, respectively. Treatment was generally well tolerated. Phase III trials of Promacta are currently underway.

March 24, 2003

Baxter reported positive results from a pivotal phase III trial investigating the Intercept Blood System, a blood safety technology for the prevention of transfusion-transmitted diseases. The results of the trial, called euroSPRITE indicated that the platelets treated with the system were comparable in safety and efficacy to untreated platelets. The procedure resulted in pathogen inactivated platelets while delivering the therapeutic benefits required of platelet transfusions. The randomized, double blind, controlled trial compared conventional platelets with those treated with the Intercept Blood System in 103 thrombo-cytopenic subjects. The study included subjects from the UK, France, the Netherlands and Sweden.

December 16, 2002

Celgene reported positive results from a phase II trial investigating Thalomid (thalidomide) in combination with prednisone for the treatment of myelofibrosis. The data demonstrated that 13 of 21 subjects (62%) achieved an objective clinical response that was defined by an increase in red blood cells or platelets. Seven of ten subjects (70%) who were red cell transfusion dependent responded to the combination therapy and four of the ten subjects (40%) became transfusion independent. Six of eight subjects (75%) with thrombocytopenia experienced a more than 50% increase in their platelet count. The most commonly reported adverse events were constipation, leukocytosis, mild neuropathy and mild sedation. The study enrolled 21 subjects with myelofibrosis who received 50 mg/day of Thalomid and a tapering regimen of prednisone.

September 30, 2002

In an open-label, multicenter study, GlaxoSmithKline's Argatroban was found to be safe and effective in the treatment of subjects with heparin-induced thrombocytopenia (HIT) who underwent percutaneous coronary interventions (PCI). The results showed that 98% of the 91 subjects who required PCI and received Argatroban intravenously achieved adequate anticoagulation. These subjects remained free from major complications of death, emergent coronary artery bypass graft surgery and Q-wave myocardial infarction, and only one patient experienced perioprocedural major bleeding. Successful anticoagulation was achieved by 100% of the 21 subjects who required subsequent admissions for PCI.

June 17, 2002

IDEC Pharmaceuticals has voluntarily placed a clinical hold on all ongoing clinical trials of IDEC-131, an anti-CD40 ligand monoclonal antibody. The studies have been halted due to a safety risk of thromboembolism identified by ongoing product evaluation. IDEC-131 is currently in phase II development for idiopathic thrombocytopenia purpura, Crohn's disease, psoriasis and multiple sclerosis.

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