Nplate® pivotal trials11

The pivotal trials consisted of two phase 3, parallel, double-blind studies where patients with chronic immune thrombocytopenia (ITP) who had completed at least one prior treatment were randomized to Nplate® or placebo. The primary endpoint was the achievement of a durable platelet response, defined as a weekly platelet count ≥ 50 x 109/L for at least 6 of the last 8 weeks of the 24-week treatment period in the absence of rescue therapies at any time.



See the Nplate® pivotal trials information. Learn more >

Nplate® or standard of care (SOC) trial22
Nplate® or SOC trial design22

Treatment with Nplate® or SOC was studied in a multicenter, randomized, controlled, 52-week, open-label evaluation of Nplate® and medical SOC therapy for non-splenectomized patients with ITP.

The design of this trial does not allow for comparison of Nplate® to the individual treatments received in the SOC arm.

  • Co-primary endpoints were the incidence of treatment failure and splenectomy.
  • Safety outcomes were measured as one of the secondary endpoints.
  • Concomitant therapies were allowed for both treatment groups.
  • To achieve a target platelet count of 50–200 x 109/L, Nplate® was administered once weekly at a starting dose* of 3 mcg/kg up to a maximum dose of 10 mcg/kg.
  • Treatments for patients assigned to the SOC group were selected by the investigator according to standard institutional practices or therapeutic guidelines.
Co-primary Endpoints
1. incidence of treatment failure
Study discontinuation before treatment failure
was also considered treatment failure.
Platelet count
≤ 20 x 109/L for 4 consecutive weeks at highest recommended dose of study treatment

Major bleeding event

Change in treatment
due to side effects or bleeding symptoms
Treatment Failure
2. Incidence of Splenectomy
Study discontinuation before splenectomy
was also considered splenectomy

Therapies used in SOC arm22

Therapies used in standard of care (SOC) arm
Patients could receive one or more types of SOC therapies, including watchful waiting.

Patients already receiving ITP therapies at baseline (21/157 in Nplate® group; 5/77 in SOC group) could continue receiving these throughout the trial.22

Other ITP treatments used in the Nplate® arm at any time during the 1-year trial included corticosteroids (37% of patients), immunoglobulins (7%), rituximab (1%), azathioprine (1%), danazol (2%), other medications (6%), and platelet transfusions (6%).22

Nplate® or SOC trial results
Treatment failureTreatment failure
Bleeding eventsBleeding events

Incidence of treatment failure at 1 year21

Incidence of treatment failure at 1 year
Treatment failure experience Treatment failure experience

Results were consistent with those in pivotal phase 3 trial non-splenectomized patients.1-31-3

The percentage of patients on Nplate® achieving a platelet response (> 50 x 109/L) ranged from 71% (108/152) to 92% (127/138) at any scheduled visit (weeks 2-52).22

Review Nplate® or SOC trial safety information. Learn more >

Raise and sustain platelet counts in splenectomized patients11

Deliver platelet stability and durability11

Sustained median platelet count ≥ 50 x 109/L1,21,2

Median weekly platelet count includes all patients, even those receiving rescue therapy. Error bars indicate the range from the first to the third quartiles. Light-blue line indicates platelet count of 50 x 109/L.22

Comparable results were seen in non-splenectomized patients.22

Reduce the potential for bleeding events22

Rate of grade 3 and above bleeding events22

Rate = adverse event rate per 100 patient-weeks on study medication. Rate was calculated by dividing the total number of reported events by the total number of patient-weeks and then multiplying by 100.22

Definitions of bleeding events grade 2 through 522

GRADE 2
Moderate
GRADE 3
Severe
GRADE 4
Life-threatening
GRADE 5
Fatal

In the pivotal trial with non-splenectomized patients, 10% (4/42) of Nplate® patients vs 30% (6/20) of control patients experienced a grade 2§ or above bleeding event (P = 0.04).4,54,5 Bleeding events were captured as adverse events and were not a predefined endpoint in the pivotal trial.

Rituximab is not FDA approved for use in ITP.

Including vincristine, cyclosporine, tranexamic acid, ascorbic acid, calcium, ethamsylate, pantoprazole, and Expasyl®.22 Expasyl® is a registered trademark and entire property of Pierre Rolland.

*The recommended starting dose for Nplate® is 1 mcg/kg. Please see Nplate® Prescribing Information for complete dosing instructions, including guidelines for dose adjustments. In the pivotal trials, the median dose of Nplate® was 2 mcg/kg (25th–75th percentile: 1–3 mcg/kg) in the study of non-splenectomized patients and 3 mcg/kg (25th–75th percentile: 2–7 mcg/kg) in the study of splenectomized patients.33

§Grading was per the Common Terminology Criteria for Adverse Events, v3. http://ctep.cancer.gov.22

Important Safety Information

Risk of Progression of Myelodysplastic Syndromes to Acute Myelogenous Leukemia

  • In Nplate® (romiplostim) clinical trials of patients with myelodysplastic syndromes (MDS) and severe thrombocytopenia, progression from MDS to acute myelogenous leukemia (AML) has been observed.
  • Nplate® is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP.

Thrombotic/Thromboembolic Complications

  • Thrombotic/thromboembolic complications may result from increases in platelet counts with Nplate® use. Portal vein thrombosis has been reported in patients with chronic liver disease receiving Nplate®.
  • To minimize the risk for thrombotic/thromboembolic complications, do not use Nplate® in an attempt to normalize platelet counts. Follow the dose adjustment guidelines to achieve and maintain a platelet count of ≥ 50 x 109/L.

Loss of Response to Nplate®

  • Hyporesponsiveness or failure to maintain a platelet response with Nplate® should prompt a search for causative factors, including neutralizing antibodies to Nplate®.
  • To detect antibody formation, submit blood samples to Amgen (1‑800‑772‑64361‑800‑772‑6436). Amgen will assay these samples for antibodies to Nplate® and thrombopoietin (TPO).
  • Discontinue Nplate® if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the highest weekly dose of 10 mcg/kg.

Laboratory Monitoring

  • Obtain CBCs, including platelet counts, weekly during the dose adjustment phase of Nplate® therapy and then monthly following establishment of a stable Nplate® dose.
  • Obtain CBCs, including platelet counts, weekly for at least two weeks following discontinuation of Nplate®.

Adverse Reactions

  • In the placebo-controlled trials, headache was the most commonly reported adverse drug reaction, occurring in 35% of patients receiving Nplate® and 32% of patients receiving placebo. Headaches were usually of mild or moderate severity.
  • Most common adverse reactions (≥ 5% higher patient incidence in Nplate® versus placebo) were Arthralgia (26%, 20%), Dizziness (17%, 0%), Insomnia (16%, 7%), Myalgia (14%, 2%), Pain in Extremity (13%, 5%), Abdominal Pain (11%, 0%), Shoulder Pain (8%, 0%), Dyspepsia (7%, 0%), and Paresthesia (6%, 0%).
  • Nplate® administration may increase the risk for development or progression of reticulin fiber formation within the bone marrow. This formation may improve upon discontinuation of Nplate®. In a clinical trial, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate® therapy.


Women who become pregnant during Nplate® treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program. Patients or their physicians should call 1‑800‑77‑AMGEN1‑800‑77‑AMGEN (1‑800‑772‑64361‑800‑772‑6436) to enroll.

Indication

Nplate® is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Nplate® is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than chronic ITP. Nplate® should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. Nplate® should not be used in an attempt to normalize platelet counts.

Please see full Prescribing Information and Medication Guide.

See More Close

Important Safety Information

Risk of Progression of Myelodysplastic Syndromes to Acute Myelogenous Leukemia

  • In Nplate® (romiplostim) clinical trials of patients with myelodysplastic syndromes (MDS) and severe thrombocytopenia, progression from MDS to acute myelogenous leukemia (AML) has been observed.
  • Nplate® is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP.

Thrombotic/Thromboembolic Complications

  • Thrombotic/thromboembolic complications may result from increases in platelet counts with Nplate® use. Portal vein thrombosis has been reported in patients with chronic liver disease receiving Nplate®.
  • To minimize the risk for thrombotic/thromboembolic complications, do not use Nplate® in an attempt to normalize platelet counts. Follow the dose adjustment guidelines to achieve and maintain a platelet count of ≥ 50 x 109/L.

Loss of Response to Nplate®

  • Hyporesponsiveness or failure to maintain a platelet response with Nplate® should prompt a search for causative factors, including neutralizing antibodies to Nplate®.
  • To detect antibody formation, submit blood samples to Amgen (1‑800‑772‑64361‑800‑772‑6436). Amgen will assay these samples for antibodies to Nplate® and thrombopoietin (TPO).
  • Discontinue Nplate® if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the highest weekly dose of 10 mcg/kg.

Laboratory Monitoring

  • Obtain CBCs, including platelet counts, weekly during the dose adjustment phase of Nplate® therapy and then monthly following establishment of a stable Nplate® dose.
  • Obtain CBCs, including platelet counts, weekly for at least two weeks following discontinuation of Nplate®.

Adverse Reactions

  • In the placebo-controlled trials, headache was the most commonly reported adverse drug reaction, occurring in 35% of patients receiving Nplate® and 32% of patients receiving placebo. Headaches were usually of mild or moderate severity.
  • Most common adverse reactions (≥ 5% higher patient incidence in Nplate® versus placebo) were Arthralgia (26%, 20%), Dizziness (17%, 0%), Insomnia (16%, 7%), Myalgia (14%, 2%), Pain in Extremity (13%, 5%), Abdominal Pain (11%, 0%), Shoulder Pain (8%, 0%), Dyspepsia (7%, 0%), and Paresthesia (6%, 0%).
  • Nplate® administration may increase the risk for development or progression of reticulin fiber formation within the bone marrow. This formation may improve upon discontinuation of Nplate®. In a clinical trial, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate® therapy.

Women who become pregnant during Nplate® treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program. Patients or their physicians should call 1‑800‑77‑AMGEN1‑800‑77‑AMGEN (1‑800‑772‑64361‑800‑772‑6436) to enroll.

Indication

Nplate® is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Nplate® is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than chronic ITP. Nplate® should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. Nplate® should not be used in an attempt to normalize platelet counts.

Please see full Prescribing Information and Medication Guide.

References: 1. Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008;371:395-403. 2. Kuter DJ, Rummel M, Boccia R, et al. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010;363:1889-1899. 3. Nplate® (romiplostim) prescribing information, Amgen. 4. Data on file, Amgen. 5. Gernsheimer TB, George JN, Aledort LM, et al. Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenia (ITP). J Thromb Haemost. 2010;8:1372-1382.

Back to top