Name: The Atlanta Study A prospective study of simoctocog alfa in combination with emicizumab in previously untreated / minimally treated patients and in patients with inhibitors
Uploaded: 2022-08-19
Duration: 4 min 42 s
Description: The Atlanta Study A prospective study of simoctocog alfa in combination with emicizumab in previously untreated / minimally treated patients and in patients with inhibitors.

The Atlanta Study A prospective study of simoctocog alfa in combination with emicizumab in previously untreated / minimally treated patients and in patients with inhibitors. 

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The Atlanta Study A prospective study of simoctocog alfa in combination with emicizumab in previously untreated / minimally treated patients and in patients with inhibitors

Robert F. Sidonio Jr Hemophilia of Georgia Center for Bleeding and Clotting Disorders Children’s Healthcare of Atlanta Emory University Atlanta, GA

Early initiation of prophylaxis is recommended in children with severe haemophilia. 

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Early initiation of prophylaxis is recommended in children with severe haemophilia

WFH: World Federation of Hemophilia. Srivastava A et al.  Haemophilia  2020; 26(Suppl 6):1-158.

“ For  pediatric  patients with severe  hemophilia , the WFH recommends  early initiation   of prophylaxis”

“ In the long term,  early   and regular  prophylaxis   for children reduces hemarthrosis and other  hemophilic  bleeding, produces better health and joint outcomes, reduces the number of hospital visits and admissions, and may avert the need for  orthopedic  interventions, including surgery, in the future”

The Atlanta Study. FVIII inhibitor development. FVIII inhibitors develop in about 30% of PUPs, mainly in the first 20 EDs 1. 

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FVIII inhibitors develop in about  30% of PUPs,  mainly in the first 20 EDs 1

Intensive FVIII treatment  is associated with an  increased risk  of inhibitor development 2

Immune tolerance induction (ITI)  is the only clinically proven strategy for inhibitor eradication 3

ED: exposure day; FVIII: factor VIII; PUP: previously untreated patient. 1.  Srivastava A et al.  Haemophilia  2020; 26(Suppl 6):1-158; 2.  Marcucci  M et al.  Thromb   Haemost   2015; 113:958-67; 3. Carcao M et al.  Haemophilia  2019; 25:676-84.

1. Sidonio RF Jr et al. Manuscript in preparation; 2. Batsuli G et al. Haemophilia 2019;25:789-96 ; 3. Ettingshausen CE et al. Ther Adv Hematol 2021; 12:20406207211032452.. 

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1. Sidonio RF Jr et al. Manuscript in preparation; 2.  Batsuli  G et al.  Haemophilia  2019;25:789-96 ;  3.  Ettingshausen CE et al.  Ther  Adv  Hematol   2021; 12:20406207211032452.

Concomitant emicizumab m ay facilitate the use of a low-dose FVIII regimen in PUPs to reduce the risk of inhibitor development until tolerance is established 1 Low-dose ITI with concomitant emicizumab could be a  strategy to eradicate inhibitors  while  reducing the burden of ITI therapy 2,3

Rationale  for concomitant FVIII therapy and emicizumab prophylaxis

The Atlanta Study. The Atlanta Study. Investigator-initiated phase III, two-part, prospective, open-label, multicenter study in the United States (NCT04030052). 

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Investigator-initiated  phase III, two-part,  prospective, open-label, multicenter study in the United States  (NCT04030052)

ITI in  patients with inhibitors  while on  emicizumab Part B

Part A Tolerization of  PUPs  to FVIII while on emicizumab

* MTPs can have had ≤ 2 EDs to pdFVIII , rFVIII , or a single dose of fresh frozen plasma, cryoprecipitate or packed red blood cells. FVIII:C: FVIII coagulant activity; MTP: minimally treated patient. Clinicaltrial.gov ID: NCT04030052.. 

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* MTPs can have had ≤ 2 EDs to  pdFVIII ,  rFVIII , or a single dose of fresh frozen plasma, cryoprecipitate or packed red blood cells. FVIII:C: FVIII coagulant activity; MTP: minimally treated patient. Clinicaltrial.gov ID: NCT04030052.

Aims To evaluate whether early low-dose exposure to FVIII ( simoctocog  alfa) while on  emicizumab  prophylaxis reduces inhibitor incidence To evaluate whether early exposure to  emicizumab  in infants and children < 3 years prevents life-threatening bleeds

Patients 40 PUPs or MTPs* < 3 years Moderate to severe  hemophilia  A (≤ 2% FVIII:C)  No inhibitors Status July 2022 Recruiting

Part B of the study investigates ITI in patients with inhibitors while on emicizumab

Clinicaltrial.gov ID: NCT04030052.. 7. The Atlanta Study. 

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Duration 50 FVIII EDs or 3 years  (whichever comes first)

Maintenance:  1.5 mg/kg weekly, or 3 mg/kg every 2 weeks, or  6 mg/kg every 4 weeks

Begin  1–6 months from start of emicizumab   25 ± 5 IU/kg every 7–14 days

FVIII inhibitors will be tested frequently. Clinicaltrial.gov ID: NCT04030052.. 

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Primary endpoint Cumulative incidence of inhibitors to FVIII Secondary endpoints Safety Blood levels of subclasses of neutralizing and non-neutralizing antibodies against FVIII and  emicizumab Annualized bleeding rates Dosing of  simoctocog  alfa required for treatment of acute bleeds

Every 4 EDs  or every 2 months until ED 12

Every 6 EDs  or every 3 months until ED 30

FVIII inhibitors will be tested frequently

Every 12 EDs  or every 6 months until study completion

* Patients with a previous attempt of ITI consisting < 6 months of continuous 3x/week FVIII are allowed to participate.. 

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* Patients with a previous attempt of ITI consisting < 6 months of continuous 3x/week FVIII are allowed to participate.

Aims To evaluate the efficacy of ITI with  simoctocog  alfa while on  emicizumab Status July 2022 Recruiting

Patients 20 patients < 21 years Moderate to severe hemophilia A (≤ 2% FVIII:C)  With inhibitors (> 0.6 BU/mL)*

* Loading doses of emicizumab must be completed prior to ITI with simoctocog alfa.. 

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* Loading doses of  emicizumab  must be completed prior to ITI with  simoctocog  alfa.

Maintenance:  1.5 mg/kg weekly, or 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks

Start with  emicizumab   maintenance dosing 100 IU/kg  simoctocog  alfa 3 times per week

ITI success criteria FVIII inhibitor titer < 0.6 BU/mL FVIII recovery ≥ 66% of normal FVIII half-life ≥ 6 h* Definitions of ITI success Complete success: All 3 criteria met Partial success: 2 of 3 criteria met. 

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*  Surrogate evaluation of ≥ 1% FVIII 48 hours after a 50 IU/kg/dose is allowed. rFVIIa : recombinant activated coagulation factor VII.

Primary endpoint Rate of ITI success and partial success Secondary endpoints Number of bleeding events and bleeding rate Safety Dosing of  rFVIIa  required for treatment of acute bleeds

ITI success criteria FVIII inhibitor titer < 0.6 BU/mL FVIII recovery ≥ 66% of normal FVIII half-life ≥ 6 h* Definitions of ITI success Complete success:  All  3 criteria met Partial success:  2 of 3 criteria met

The Atlanta Study. Learn more about the Atlanta Study. 

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For more information on the Atlanta Study, please contact robert.sidonio.jr@emory.edu

Robert F. Sidonio Jr.  Aflac Cancer and Blood Disorders Center Emory University/Children’s Healthcare of Atlanta

Shannon Meeks Emory University/Aflac Cancer and Blood Disorders Center

Michael Callaghan Children’s Hospital of Michigan/Wayne State University

Marilyn Manco-Johnson  University of Colorado/ Hemophilia and Thrombosis Center

Amy Shapiro Indiana Hemophilia and Thrombosis Center

The Atlanta Study
A prospective study of simoctocog alfa in combination with emicizumab in previously untreated / minimally treated patients and in patients with inhibitors

The Atlanta Study A prospective study of simoctocog alfa in combination with emicizumab in previously untreated / minimally treated patients and in patients with inhibitors

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