A Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Emicizumab in Participants With Mild or Moderate Hemophilia A Without FVIII Inhibitors

NCT04158648 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: BO414232019-002179-322023-506610-52-00
• Study Type: interventional
• Target: 73
• Locations: 10 countries
• Sites: 22

Brief Summary

This is a multicenter, open-label, single-arm study designed to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of emicizumab in participants with mild or moderate hemophilia A without inhibitors against factor VIII (FVIII).

Conditions

Mild Hereditary Factor VIII Deficiency Disease Without Inhibitor; Moderate Hereditary Factor VIII Deficiency Disease Without Inhibitor; Hemophilia A

Keywords

Mild Hemophilia A Without Factor VIII Inhibitors; Moderate Hemophilia A Without Factor VIII Inhibitors

Outcome Measures

Primary Outcomes (3)

• Model-Based Annualized Bleed Rate for Treated Bleeds

  The number of treated bleeds over the efficacy period was estimated as an annualized bleed rate (ABR) using a negative binomial regression model, which accounts for different follow-up times. A treated bleed was defined as a bleed that was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.

  From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)

• Mean Calculated Annualized Bleed Rate for Treated Bleeds

  The number of treated bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated bleed was defined as a bleed that was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.

  From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)

• Median Calculated Annualized Bleed Rate for Treated Bleeds

  The number of treated bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated bleed was defined as a bleed that was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.

  From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)

Secondary Outcomes (61)

• Model-Based Annualized Bleed Rate for All Bleeds

  From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)

• Mean Calculated Annualized Bleed Rate for All Bleeds

  From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)

• Median Calculated Annualized Bleed Rate for All Bleeds

  From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)

• Model-Based Annualized Bleed Rate for Treated Joint Bleeds

  From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)

• Mean Calculated Annualized Bleed Rate for Treated Joint Bleeds

  From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)

Study Arms (1)

Emicizumab

EXPERIMENTAL

Participants with mild and moderate hemophilia A without factor VIII (FVIII) inhibitors will be enrolled to receive the emicizumab loading dose regimen followed by the participant's preference of one of 3 maintenance dose regimens.

Drug: Emicizumab

Interventions

Emicizumab DRUG

Four loading doses of emicizumab 3 milligrams per kilogram of body weight (mg/kg) will be administered subcutaneously (SC) once a week (QW) for 4 weeks followed by participant's preference of one of the three following maintenance SC dose regimens: 1.5 mg/kg QW, 3 mg/kg once every 2 weeks (Q2W), or 6 mg/kg once every 4 weeks (Q4W).

Also known as: Hemlibra, RO5534262, RG6013, ACE910

Emicizumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of mild (FVIII level between \>5% and \<40%) or moderate (FVIII level between ≥1% and ≤5%) congenital Hemophilia A without FVIII inhibitors
• Weight ≥3 kilograms (kg)
• Need for prophylaxis based on investigator assessment
• A negative test for inhibitor (i.e., \<0.6 Bethesda Units per milliliter \[BU/mL\]) within 8 weeks prior to enrollment
• No documented inhibitor (i.e., \<0.6 BU/mL), FVIII half-life \<6 hours, or FVIII recovery \<66% in the last 5 years
• Documentation of the details of prophylactic or episodic FVIII treatment and of number of bleeding episodes for at least the last 24 weeks prior to enrollment
• Adequate hematologic, hepatic, and renal function
• For women of childbearing potential: agreement to remain abstinent or use contraception (as defined in the protocol) during the treatment period and for at least 24 weeks after the final dose of study drug

You may not qualify if:

• Inherited or acquired bleeding disorder other than mild or moderate congenital hemophilia A
• History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the investigator's judgment
• Previous (within the last 12 months) or current treatment for thromboembolic disease or signs of thromboembolic disease
• Other conditions that may currently increase the risk of bleeding or thrombosis
• History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
• Planned surgery during the emicizumab loading dose phase (surgeries in participants on emicizumab from Week 5 onwards are allowed)
• Known HIV infection with CD4 counts \<200 cells per microlitre (/μL)
• Concomitant disease, condition, significant abnormality on screening evaluation or laboratory tests, or treatment that could interfere with the conduct of the study, or that would in the opinion of the investigator, pose an additional unacceptable risk in administering study drug to the participant
• Receipt of any of the following: An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration with the exception of prior emicizumab prophylaxis; A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter; or Any other investigational drug currently being administered or planned to be administered
• Inability to comply with the study protocol in the opinion of the investigator
• Pregnant or breastfeeding, or intending to become pregnant during the study (women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (22)

Childrens Hospital LA

Los Angeles, California, 90027, United States

Location

Hemophilia of Georgia Center for Bleeding & Clotting Disorders

Atlanta, Georgia, 30308, United States

Location

Indiana Hemophilia & Thrombosis center

Indianapolis, Indiana, 46260, United States

Location

University of Michigan, C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Washington Institute for Coagulation

Seattle, Washington, 98101, United States

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Kaye Edmonton Clinic

Edmonton, Alberta, T6G 1Z1, Canada

Location

Eastern Health - General Hospital

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Hopital Cardio-vasculaire Louis Pradel

Bron, 69677, France

Location

CH de Bicetre

Le Kremlin-Bicêtre, 94275, France

Location

Groupe Hospitalier Necker Enfants Malades

Paris, 75015, France

Location

Universitätsklinikum Bonn

Bonn, 53127, Germany

Location

Klinikum der Universität München, Campus Innenstadt

München, 80336, Germany

Location

Amsterdam UMC Location AMC

Amsterdam, 1105 AZ, Netherlands

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

Location

Charlotte Maxeke Johannesburg Hospital

Johannesburg, 2193, South Africa

Location

Hospital Universitario la Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Cardiff and Vale NHS Trust

Cardiff, CF14 4XW, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Great Ormond street Hospital for Children NHS Foundation Trust

London, WC1N 3HR, United Kingdom

Location

Related Publications (1)

• Negrier C, Mahlangu J, Lehle M, Chowdary P, Catalani O, Bernardi RJ, Jimenez-Yuste V, Beckermann BM, Schmitt C, Ventriglia G, Windyga J, d'Oiron R, Moorehead P, Koparkar S, Teodoro V, Shapiro AD, Oldenburg J, Hermans C. Emicizumab in people with moderate or mild haemophilia A (HAVEN 6): a multicentre, open-label, single-arm, phase 3 study. Lancet Haematol. 2023 Mar;10(3):e168-e177. doi: 10.1016/S2352-3026(22)00377-5. Epub 2023 Jan 27.

  PMID: 36716761 DERIVED

MeSH Terms

Conditions

Hemophilia A

Interventions

emicizumab

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 12, 2019
• Study Start: February 10, 2020
• Primary Completion: October 30, 2021
• Study Completion: December 19, 2025
• Last Updated: January 23, 2026
• Results First Posted: December 15, 2022

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

PL (1); DE (2); FR (3); US (5); ZA (1); CA (2); ES (2); NL (1); GB (3); BE (2)