A Study to Assess the Efficacy and Safety of Efgartigimod IV in Adult Participants With Primary Immune Thrombocytopenia (advance NEXT)


Purpose of this study?

 

The main purpose of this study is to look at the effect (efficacy) and safety of efgartigimod IV in participants with primary immune thrombocytopenia (ITP). After an up to 2 weeks screening period, eligible participants will be randomized in a 2:1 ratio to receive either efgartigimod IV or placebo IV, respectively during the double-blinded treatment period (DBTP). At the end of the treatment period (up to 24 weeks), all participants will receive efgartigimod IV during the first 52-week open-label treatment period (OLTP1). At the end of the first OLTP1, participants may begin a second 52-week OLTP2. After the OLTP2, the participants will enter a follow-up period (approximately 8 weeks) while off study drug. The participants will be in the study for up to 138 weeks.

 

Inclusion Criteria:

 

  • Is at least 18 years of age and the local legal age of consent for clinical studies when signing the informed consent form (ICF).
  • Has documented baseline mean platelet count of <30 x 10^9/L before randomization
  • Has a documented duration of primary immune thrombocytopenia (ITP) of more than 12 months on the date of informed consent form (ICF) signature.
  • Has documented prior ITP treatment with at least 1 of the following treatments: corticosteroids, intravenous immunoglobulin (IVIg), anti-D immunoglobulin, thrombopoietin receptor agonist (TPO-RAs), or rituximab.
  • Has documented insufficient response to a prior ITP treatment (the specific criteria can be found in the protocol).
  • Has documented prior response defined as 1 platelet count of ≥50 × 109/L to at least 1 of the following ITP treatments in the 3 years before the date of ICF signature: prednisone, dexamethasone, other or nonspecified corticosteroids, IVIg, or anti-D immunoglobulin

 

Exclusion Criteria:

 

  • Other than the indication under study, known autoimmune disease or any medical condition that would interfere with an accurate assessment of clinical symptoms of ITP, confound the results of the study or put the participant at undue risk.
  • Secondary ITP
  • Nonimmune thrombocytopenia
  • Autoimmune hemolytic anemia
  • ITP-associated critical or severe bleeding The complete list of criteria can be found in the protocol.

 

 

 

Primary outcome measures:

 

  • Extent of disease control, defined as the number of cumulative weeks during the 24-week Double-Blinded Treatment Period with platelet counts of at least 50 × 10^9/L [Time Frame: Up to 24 weeks]

 

 

Secondary outcome measures:

 

  • - Proportion of participants achieving platelet counts of at least 50 × 10^9/L for at least 4 of the 6 study visits between study weeks 19 and 24 of the DBTP [Time Frame: Up to 6 weeks]
  • Proportion of participants achieving platelet counts of at least 50 × 10^9/L for at least 6 of the 8 study visits between study weeks 17 and 24 of the DBTP [Time Frame: Up to 8 weeks]
  • Proportion of participants achieving a platelet counts of at least 50 × 10^9/L for at least 8 of the 12 study visits between weeks 13 and 24 of the DBTP [Time Frame: Up to 12 weeks]
  • Proportion of participants achieving a platelet count of at least 50 × 10^9/L on at least 4 occasions at any time until study week 12 during the DBTP [Time Frame: Up to 12 weeks]
  • Time to response, defined as the time to achieve 2 consecutive platelet counts of at least 50 × 10^9/L at any time during the DBTP [Time Frame: up to 24 weeks]
  • Proportion of participants with an IWG response during the DBTP [Time Frame: Up to 24 weeks]
  • International Working Group (IWG)
  • Proportion of participants with initial response, defined as a platelet count of at least 30 × 10^9/L and a 2-fold increase from baseline in platelet count at study week 5 of the DBTP [Time Frame: Up to 20 weeks]
  • Time to achieve a platelet count of at least 30 × 10^9/L and a 2-fold increase from baseline in platelet count during the DBTP [Time Frame: Up to 24 weeks]
  • Number of cumulative weeks during the DBTP with platelet counts of at least 30 × 10^9/L and ≥20 × 10^9/L above baseline [Time Frame: Up to 24 weeks]
  • Number of cumulative weeks during the DBTP with platelet counts of at least 30 × 10^9/L and at least 20 × 10^9/L above baseline in participants with baseline platelet counts of <15 × 10^9/L [Time Frame: Up to 24 weeks]
  • Extent of disease control, defined as the percentage of weeks with platelet counts of at least 50 × 10^9/L [Time Frame: Up to 76 weeks]
  • In participants receiving placebo IV in the DBTP, the extent of disease control, defined as the number of cumulative weeks with platelet counts of at least 50 × 10^9/L [Time Frame: Up to 76 weeks]
  • Overall platelet count response, defined as the proportion of participants achieving a platelet count of at least 50 × 10^9/L on at least 4 occasions during the first 52 weeks of treatment with efgartigimod IV [Time Frame: Up to 52 weeks]
  • Mean change from baseline in platelet count at each study visit [Time Frame: Up to 76 weeks]
  • The percentage of weeks with platelet counts of at least 30 × 10^9/L and at least 20 × 10^9/L above baseline [Time Frame: Up to 76 weeks]
  • In participants with baseline platelet counts <15 × 10^9/L, the percentage of weeks with platelet counts of at least 30 × 10^9/L and at least 20 × 10^9/L above baseline [Time Frame: Up to 76 weeks]
  • Proportion of participants who achieve a sustained platelet count response, defined as achieving platelet counts of at least 50 × 10^9/L for at least 4 occasions during 6-week intervals [Time Frame: Up to 76 weeks]
  • In participants receiving placebo IV in the DBTP, the proportion of participants achieving platelet counts of at least 50 × 10^9/L for at least 8 of the 12 study visits between weeks 13 and 24 of the OLTP1 [Time Frame: Up to 12 weeks]
  • In participants receiving placebo IV in the DBTP, proportion of participants who achieve sustained platelet count response, defined as achieving platelet counts of at least 50 × 10^9/L for at least 6 of 8 visits between weeks 17 and 24 of the OLTP1 [Time Frame: Up to 8 weeks]
  • In participants receiving placebo IV in the DBTP, the extent of disease control, defined as the number of cumulative weeks with platelet counts of at least 50 × 10^9/L during the first 24 weeks of treatment with efgartigimod IV [Time Frame: Up to 24 weeks]
  • Occurrence rate of rescue ITP therapy [Time Frame: Up to 76 weeks]
  • Proportion of participants with reduction in concurrent ITP therapy during the OLTP1 [Time Frame: Up to 52 weeks]
  • Incidence and severity of bleeding, assessed by the ITP Bleeding Scale (IBLS) [Time Frame: Up to 76 weeks]
  • Incidence of AEs (including AEs of clinical interest) and SAEs [Time Frame: Up to 136 weeks]
  • AE = adverse event; SAE = serious adverse event; An adverse event of clinical interest is a pre-specified medically significant event that has the potential to be causally associated with the study drug.
  • Incidence of ADA against efgartigimod in serum over time [Time Frame: Up to 136 weeks]
  • ADA = antidrug antibodies
  • Incidence of NAb against efgartigimod in serum over time [Time Frame: Up to 136 weeks]
  • NAb = Neutralizing antibodies
  • Efgartigimod Cmax over time [Time Frame: Up to 136 weeks]
  • Percent change from baseline in total IgG levels in serum over time [Time Frame: Up to 136 weeks]
  • IgG = immunoglobulin G

 

 

Study Locations in Europe: Austria, Bulgaria, Croatia, Czechia, France, Germany, Hungary, Ireland, Italy, Poland, Portugal, Romania, Serbia, Spain, UK

 

Estimated Study Completion Date:  2028-06

 

Further information on clinicaltrials.gov – trial number NCT06544499