Emicizumab in Patients With Acquired Hemophilia A

Acquired Hemophilia A Clinical Trial

— AHAEmi  

Official title:

Emicizumab in Patients With Acquired Hemophilia A: Multicenter, Single-arm, Open-label Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05345197
• Other study ID #: STUDY00013920
• Status: Recruiting
• Phase: Phase 2
• Start date: August 31, 2022
• Est. completion date: January 2025

Study information

• Verified date: April 2024
• Source: University of Washington
• Contact: Danielle Matia, MPH
• Phone: 206-614-1157
• Email: danielle.matia[@]wacbd.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase II multicenter open-label, single-arm prospective study to evaluate the efficacy of prophylactic emicizumab administered on a scheduled basis to prevent bleeds in patients with acquired hemophilia A (AHA).

Description:

Patients with AHA who are eligible will receive two loading doses of the study drug, emicizumab (6mg/kg on day 1 and 3 mg/kg on day 2) followed by once weekly subcutaneous emicizumab (1.5 mg/kg). Immunosuppression will be given concurrently as per investigator discretion. The primary endpoint (bleed rate) will be assessed after 12 weeks on study drug. If partial remission of the AHA has not been achieved, an additional 12 weeks of study drug may be given. A historical cohort and a study conducted in parallel in Germany (NCT04188639) will serve as control groups for evaluation of secondary endpoints provided the study cohort are comparable.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 51
• Est. completion date: January 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed Informed Consent/Assent Form
• Age =18 years at time of signing Informed Consent Form
• Ability to comply with the study protocol, in the investigator's judgment
• Diagnosis of AHA based on a reduced FVIII activity (<50 %) and positive FVIII inhibitor (>0.6 BU/ml) at screening (local laboratory)
• Current bleeding due to AHA at the time of screening
• Plan to be adherent to emicizumab prophylaxis during the study
• For women of childbearing potential who meet the following criteria:
• Refrain from heterosexual intercourse or use contraceptive methods that result in a failure rate of <1% per year during the study period A woman with = 12 continuous months of amenorrhea with no identified cause other than menopause and has not undergone surgical sterilization (removal of ovaries and/or uterus). use of combined oral or injected hormonal contraceptive, bilateral tubal ligation, male sterilization, hormone- releasing intrauterine devices, and copper intrauterine devices.

Exclusion Criteria:

• Congenital hemophilia A
• Treatment with aPCC within the last 24 hours before first study treatment or planned treatment with aPCC during the course of the study
• Known positive lupus anticoagulant at the time of screening
• Severe uncontrolled infection at the time of screening
• Signs of active disseminated intravascular coagulation at the time of screening -
• Emicizumab ? AHA Emi Version 1.0 20
• Current treatment for thromboembolic disease or signs of current thromboembolic disease at time of screening
• Patients who are at high risk for TMA (e.g., have a previous medical or family history of TMA), in the investigator's judgment
• Known severe congenital or acquired thrombophilia
• Life expectancy <3 months at the time of screening
• Other conditions that substantially increase risk of bleeding or thrombosis by the discretion of the investigator
• Contraindications according to the Investigator's Brochure of emicizumab
• Current treatment with emicizumab at time of screening
• History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection by the discretion of the investigator
• Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose additional risk, or would, in the opinion of the local investigator, preclude the patient's safe participation in and completion of the study
• Addiction or other diseases that preclude the patient from appropriately assessing the nature and scope as well as possible consequences of the clinical study by the discretion of the investigator
• Pregnant or breast-feeding women
• Would refuse treatment with blood or blood products, if necessary.
• Subject is in custody by order of an authority or a court of law
• Treatment with any of the following:
• An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration before Study Day 1
• A non-hemophilia-related investigational drug within the last 30 days or 5 half-lives- before Study Day 1, whichever is longer
• An investigational drug concurrently
• History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection

Related Conditions & MeSH terms

• Acquired Hemophilia A
• Hemophilia A

Intervention

Drug:
• emicizumab
This study design uses emicizumab as a prophylaxis treatment to prevent bleeding for all participants, bypassing agents (with the exception of aPCC) and treatment of concomitant diseases will be given as clinically indicated. All eligible subjects with AHA will receive the same study medication consisting of: two loading doses of the emicizumab on day 1 and 2 followed by once weekly subcutaneous emicizumab injections. Immunosuppressive therapy (IST) will be given concurrently as per investigator discretion.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Indiana Hemophilia and Thrombosis Center, Inc.	Indianapolis	Indiana
United States	Bleeding and Clotting Disorders Institute	Peoria	Illinois
United States	Mayo Clinic	Rochester	Minnesota
United States	UCSD Hemophilia and Thrombosis Treatment Center	San Diego	California
United States	Washington Center for Bleeding Disorders	Seattle	Washington
United States	Georgetown University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (28)

Al-Banaa K, Alhillan A, Hawa F, Mahmood R, Zaki A, El Abdallah M, Zimmerman J, Musa F. Emicizumab Use in Treatment of Acquired Hemophilia A: A Case Report. Am J Case Rep. 2019 Jul 18;20:1046-1048. doi: 10.12659/AJCR.916783. — View Citation

Collins PW, Liesner R, Makris M, Talks K, Chowdary P, Chalmers E, Hall G, Riddell A, Percy CL, Hay CR, Hart DP. Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee. Haemophilia. 2018 May;24(3):344-347. doi: 10.1111/hae.13495. — View Citation

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Langer AL, Etra A, Aledort L. Evaluating the safety of emicizumab in patients with hemophilia A. Expert Opin Drug Saf. 2018 Dec;17(12):1233-1237. doi: 10.1080/14740338.2019.1551356. Epub 2018 Nov 28. — View Citation

Levy GG, Asikanius E, Kuebler P, Benchikh El Fegoun S, Esbjerg S, Seremetis S. Safety analysis of rFVIIa with emicizumab dosing in congenital hemophilia A with inhibitors: Experience from the HAVEN clinical program. J Thromb Haemost. 2019 Sep;17(9):1470-1477. doi: 10.1111/jth.14491. Epub 2019 Jun 17. — View Citation

Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, Schmitt C, Jimenez-Yuste V, Kempton C, Dhalluin C, Callaghan MU, Bujan W, Shima M, Adamkewicz JI, Asikanius E, Levy GG, Kruse-Jarres R. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. N Engl J Med. 2018 Aug 30;379(9):811-822. doi: 10.1056/NEJMoa1803550. — View Citation

Mahlangu J. Emicizumab for the prevention of bleeds in hemophilia A. Expert Opin Biol Ther. 2019 Aug;19(8):753-761. doi: 10.1080/14712598.2019.1626370. Epub 2019 Jun 13. — View Citation

Mohnle P, Pekrul I, Spannagl M, Sturm A, Singh D, Dechant C. Emicizumab in the Treatment of Acquired Haemophilia: A Case Report. Transfus Med Hemother. 2019 Apr;46(2):121-123. doi: 10.1159/000497287. Epub 2019 Mar 15. — View Citation

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Muto A, Yoshihashi K, Takeda M, Kitazawa T, Soeda T, Igawa T, Sampei Z, Kuramochi T, Sakamoto A, Haraya K, Adachi K, Kawabe Y, Nogami K, Shima M, Hattori K. Anti-factor IXa/X bispecific antibody ACE910 prevents joint bleeds in a long-term primate model of acquired hemophilia A. Blood. 2014 Nov 13;124(20):3165-71. doi: 10.1182/blood-2014-07-585737. Epub 2014 Oct 1. — View Citation

Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, Santagostino E, Kruse-Jarres R, Negrier C, Kessler C, Valente N, Asikanius E, Levy GG, Windyga J, Shima M. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med. 2017 Aug 31;377(9):809-818. doi: 10.1056/NEJMoa1703068. Epub 2017 Jul 10. — View Citation

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Pipe SW, Shima M, Lehle M, Shapiro A, Chebon S, Fukutake K, Key NS, Portron A, Schmitt C, Podolak-Dawidziak M, Selak Bienz N, Hermans C, Campinha-Bacote A, Kiialainen A, Peerlinck K, Levy GG, Jimenez-Yuste V. Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study. Lancet Haematol. 2019 Jun;6(6):e295-e305. doi: 10.1016/S2352-3026(19)30054-7. Epub 2019 Apr 16. — View Citation

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Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, Fukazawa N, Yoneyama K, Yoshida H, Nogami K. Factor VIII-Mimetic Function of Humanized Bispecific Antibody in Hemophilia A. N Engl J Med. 2016 May 26;374(21):2044-53. doi: 10.1056/NEJMoa1511769. — View Citation

Takeyama M, Nogami K, Matsumoto T, Noguchi-Sasaki M, Kitazawa T, Shima M. An anti-factor IXa/factor X bispecific antibody, emicizumab, improves ex vivo coagulant potentials in plasma from patients with acquired hemophilia A. J Thromb Haemost. 2020 Apr;18(4):825-833. doi: 10.1111/jth.14746. Epub 2020 Feb 26. — View Citation

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Tiede A, Klamroth R, Scharf RE, Trappe RU, Holstein K, Huth-Kuhne A, Gottstein S, Geisen U, Schenk J, Scholz U, Schilling K, Neumeister P, Miesbach W, Manner D, Greil R, von Auer C, Krause M, Leimkuhler K, Kalus U, Blumtritt JM, Werwitzke S, Budde E, Koch A, Knobl P. Prognostic factors for remission of and survival in acquired hemophilia A (AHA): results from the GTH-AH 01/2010 study. Blood. 2015 Feb 12;125(7):1091-7. doi: 10.1182/blood-2014-07-587089. Epub 2014 Dec 18. — View Citation

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Young G, Callaghan M, Dunn A, Kruse-Jarres R, Pipe S. Emicizumab for hemophilia A with factor VIII inhibitors. Expert Rev Hematol. 2018 Nov;11(11):835-846. doi: 10.1080/17474086.2018.1531701. Epub 2018 Oct 10. — View Citation

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Comparison of historic GTH-AH 01/2020 cohort/ Number of clinically significant bleeds	Number of clinically significant bleeds in the 12 weeks of emicizumab treatment or until achieving partial remission (PR) of AHA, whatever occurs first Incidence and severity of adverse events, thromboembolic events, thrombotic microangiopathy, in 12 weeks of treatment and mortality after 24 weeks Bleeding-free survival until week 12 after starting treatment	12 to 24 weeks
Other	Comparison to a parallel German study cohort/ Number of clinically significant bleeds	Number of clinically significant bleeds per patient-week until death or week 12 after starting emicizumab treatment, whatever occurs first Incidence and severity of adverse events, thromboembolic events, in the 12 weeks of emicizumab treatment and mortality after 24 weeks Bleeding-free survival until week 12 of emicizumab treatment	12 to 24 weeks
Primary	Primary Outcome Meassure	Number of clinically significant bleeds after 12 weeks of study drug (emicizumab)	12 weeks
Secondary	Incidence and severity of adverse events	Incidence and severity of adverse events, including thromboembolic events, thrombotic microangiopathy in the 12 weeks after starting emicizumab treatment; mortality and cause of death in the 24 weeks after starting emicizumab treatment.	duration of entire study
Secondary	Days of treatment with additional hemostatic agent	Days of treatment with and total dose of bypassing agents (recombinant factor VIIa, activated prothrombin complex concentrate) or recombinant porcine factor VIII (susoctocag alfa) or other factor VIII concentrates; specifics (drug, amount and timing) of IST started during the 12 weeks of emicizumab prophylaxis	12 weeks
Secondary	Remission Rate	Number of patients achieving partial remission (PR) and complete remission (CR) over 12 and 24 weeks after starting emicizumab prophylaxis	1 to 24 weeks
Secondary	Hospitalizations	Days in hospital during week 12 of emicizumab treatment	12 weeks
Secondary	Total dose of additional hemostatic agent	Total dose of bypassing agents (recombinant factor VIIa, activated prothrombin complex concentrate) or recombinant porcine factor VIII (susoctocag alfa) or other factor VIII concentrates; specifics (drug, amount and timing) of IST started during the 12 weeks of emicizumab prophylaxis	12 weeks