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NCT00472290

Evaluating the Safety of Long Term Dosing of Romiplostim (Formerly AMG 531) in Thrombocytopenic Subjects With Myelodysplastic Syndromes (MDS)

Completed NA Results posted Last updated 29 December 2017
What this trial tests

NA trial testing Romiplostim (formerly AMG 531) in Hematology in 72 participants. Completed in 26 December 2011.

Timeline
1 April 2007
Primary endpoint
18 July 2011
26 December 2011

Quick facts

Lead sponsorAmgen
PhaseNA
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment72
Start date1 April 2007
Primary completion18 July 2011
Estimated completion26 December 2011

Drugs / interventions tested

Conditions studied

Sponsor

Amgen — full company profile →

Who can join

18 and older, any sex, with Hematology or MDS. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Summary of Adverse Events Primary · During treatment period from first dose of IP to End of Study visit, on Average 56 Weeks .
Subjects Reporting Any AE
GroupValue95% CI
Romiplostim71
Subjects Reporting Any Treatment-related AE
GroupValue95% CI
Romiplostim19
Subjects Reporting Any Treat-related Serious AE
GroupValue95% CI
Romiplostim4
Subjects Reporting Any Serious AE
GroupValue95% CI
Romiplostim29
Subjects Withdrew Study or Stop IP Due to AE
GroupValue95% CI
Romiplostim8
Weekly Bleeding Events Per 100 Subject Years Secondary · During the treatment period. The average duration of romiplostim exposure is 56 weeks.

During the time since the first dose of IP to the end of the treatment period. A single bleeding event was defined as each individual bleeding episode that originated from a specific organ system (eg, gastrointestinal system or central nervous system). A bleeding event that continued for more than 7 days was counted as separate events every eighth day.

GroupValue95% CI
Romiplostim1120.51047.1 – 1197.7
Platelet Transfusion Events Per 100 Subject Years Secondary · During the treatment period. The average duration of romiplostim exposure is 56 weeks.

During the time since the first dose of IP to the end of the treatment period. A discrete platelet transfusion event was defined as any number of platelet transfusions administered within a 3-day period. Platelet transfusions administered more than 3 days apart were counted as separate platelet transfusion events.

GroupValue95% CI
Romiplostim204.4173.8 – 238.9
Weeks With Platelet Response Per Year Secondary · During the treatment period. The average duration of romiplostim exposure is 56 weeks.

During the time since the first dose of IP to the end of the treatment period. Platelet response was based on the modified IWG 2006 criteria (Cheson et al, 2006) and was defined as, in the absence of platelet transfusion: an absolute increase in platelet count of ≥ 30 x 10\^9/L for a subject starting with a platelet count of ≥ 20 x 10\^9/L; or an increase in platelet count from \< 20 x 10\^9/L to ≥ 20 x 10\^9/L and by at least 100% in a subject that started with a platelet count \< 20 x 10\^9/L.

GroupValue95% CI
Romiplostim34.633.3 – 35.9
Time to First Platelet Response Secondary · During treatment period. The average duration of romiplostim exposure is 56 weeks.

Time since first dose of IP to the first platelet response. Platelet response was based on the modified IWG 2006 criteria (Cheson et al, 2006) and was defined as, in the absence of platelet transfusion: an absolute increase in platelet count of ≥ 30 x 10\^9/L for a subject starting with a platelet count of ≥ 20 x 10\^9/L; or an increase in platelet count from \< 20 x 10\^9/L to ≥ 20 x 10\^9/L and by at least 100% in a subject that started with a platelet count \< 20 x 10\^9/L.

GroupValue95% CI
Romiplostim2.32.1 – 3.1
Duration of Platelet Response Secondary · During treatment period. The average duration of romiplostim exposure is 56 weeks.

Platelet response was based on the modified IWG 2006 criteria (Cheson et al, 2006) and was defined as, in the absence of platelet transfusion: an absolute increase in platelet count of ≥ 30 x 10\^9/L for a subject starting with a platelet count of ≥ 20 x 10\^9/L; or an increase in platelet count from \< 20 x 10\^9/L to ≥ 20 x 10\^9/L and by at least 100% in a subject that started with a platelet count \< 20 x 10\^9/L.

GroupValue95% CI
Romiplostim20.01 – 159
Incidence of Antibody (AB) Formation Primary · During treatment period from first dose of IP to End of Study visit, on Average 56 Weeks.
Positive binding AB to IP at or before baseline
GroupValue95% CI
Romiplostim5± 94.7
Neutralizing AB to IP at or before baseline
GroupValue95% CI
Romiplostim0
Binding AB positive to IP post-baseline only
GroupValue95% CI
Romiplostim5
Persistent binding AB positive to IP
GroupValue95% CI
Romiplostim4
Transient binding AB positive to IP
GroupValue95% CI
Romiplostim1
Positive binding AB to TPO at or before baseline
GroupValue95% CI
Romiplostim4
Neutralizing AB to TPO at or before baseline
GroupValue95% CI
Romiplostim0
Binding AB positive to TPO post-baseline only
GroupValue95% CI
Romiplostim3

Adverse events — posted to ClinicalTrials.gov

Time frame: The average duration is 56 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Romiplostim
Serious: 29/72 (40%)
Deaths:

Serious adverse events (60 terms)

ReactionSystemRomiplostim
PneumoniaInfections and infestations
HaematomaVascular disorders
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
BronchitisInfections and infestations
Urinary tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
AnxietyPsychiatric disorders
HaematuriaRenal and urinary disorders
Renal failure acuteRenal and urinary disorders
LymphadenopathyBlood and lymphatic system disorders
PancytopeniaBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
Cardiac failure congestiveCardiac disorders
Coronary artery diseaseCardiac disorders
Myocardial infarctionCardiac disorders
TachycardiaCardiac disorders
Muscular dystrophyCongenital, familial and genetic disorders
ColitisGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Intestinal perforationGastrointestinal disorders
Mouth haemorrhageGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Varices oesophagealGastrointestinal disorders
Other adverse events (49 terms — click to expand)

ReactionSystemRomiplostim
EpistaxisRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
ContusionInjury, poisoning and procedural complications
ConstipationGastrointestinal disorders
HeadacheNervous system disorders
HaematomaVascular disorders
PyrexiaGeneral disorders
Upper respiratory tract infectionInfections and infestations
Back painMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
Gingival bleedingGastrointestinal disorders
VomitingGastrointestinal disorders
EcchymosisSkin and subcutaneous tissue disorders
Eye haemorrhageEye disorders
NasopharyngitisInfections and infestations
DizzinessNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HaemorrhoidsGastrointestinal disorders
NauseaGastrointestinal disorders
AstheniaGeneral disorders
PainGeneral disorders
Urinary tract infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Blood blisterSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
ThrombocytopeniaBlood and lymphatic system disorders
Oedema peripheralGeneral disorders
BronchitisInfections and infestations
Weight decreasedInvestigations
Muscle spasmsMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
DepressionPsychiatric disorders
InsomniaPsychiatric disorders
PalpitationsCardiac disorders
Mouth haemorrhageGastrointestinal disorders

Most-reported serious reactions: Pneumonia, Haematoma, Anaemia, Febrile neutropenia, Bronchitis, Urinary tract infection, Arthralgia, Anxiety.

Data from ClinicalTrials.gov NCT00472290 adverse events section.

Sponsor's own description

This is an open label extension study of romiplostim for treatment of thrombocytopenia (platelet count ≤ 50 x 10\^9/L) in MDS subjects. The study is designed to assess the long-term safety of treatment with romiplostim, as measured by incidence of overall adverse events, the incidence of bleeding events, the utilization of platelet transfusions, and the duration of platelet response. The study will further describe the time to disease progression to acute myeloid leukemia (AML) and survival.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Romiplostim monotherapy in thrombocytopenic patients with myelodysplastic syndromes: long-term safety and efficacy.
    Fenaux P, Muus P, Kantarjian H, Lyons RM, et al · · 2017 · cited 38× · PMID 28616874 · DOI 10.1111/bjh.14792
  2. Alternatives, and adjuncts, to prophylactic platelet transfusion for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation.
    Desborough M, Estcourt LJ, Doree C, Trivella M, et al · · 2016 · cited 10× · PMID 27548292 · DOI 10.1002/14651858.cd010982.pub2
  3. Off-Label Use of Thrombopoietin Receptor Agonists: Case Series and Review of the Literature.
    Capecchi M, Serpenti F, Giannotta J, Pettine L, et al · · 2021 · cited 6× · PMID 34650908 · DOI 10.3389/fonc.2021.680411

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