Phase 3
N=73
A Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Emicizumab in Participants With Mild or Moderate Hemophilia A Without FVIII Inhibitors
Mild Hereditary Factor VIII Deficiency Disease Without Inhibitor · Moderate Hereditary Factor VIII Deficiency Disease Without Inhibitor · Hemophilia A
Bottom Line
View on ClinicalTrials.gov: NCT04158648 ↗Enrolled (actual)
73
Serious AEs
11.1%
Results posted
Dec 2022
Primary outcome: Primary: Model-Based Annualized Bleed Rate for Treated Bleeds — 0.9 Treated bleeds per year
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Emicizumab (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Oct 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Model-Based Annualized Bleed Rate for Treated Bleeds |
0.9 | — |
| PRIMARY Mean Calculated Annualized Bleed Rate for Treated Bleeds |
0.9 | — |
| PRIMARY Median Calculated Annualized Bleed Rate for Treated Bleeds |
0.0 | — |
| SECONDARY Model-Based Annualized Bleed Rate for All Bleeds |
2.3 | — |
| SECONDARY Mean Calculated Annualized Bleed Rate for All Bleeds |
2.3 | — |
| SECONDARY Median Calculated Annualized Bleed Rate for All Bleeds |
1.0 | — |
| SECONDARY Model-Based Annualized Bleed Rate for Treated Joint Bleeds |
0.2 | — |
| SECONDARY Mean Calculated Annualized Bleed Rate for Treated Joint Bleeds |
0.2 | — |
| SECONDARY Median Calculated Annualized Bleed Rate for Treated Joint Bleeds |
0.0 | — |
| SECONDARY Model-Based Annualized Bleed Rate for Treated Target Joint Bleeds |
0.1 | — |
| SECONDARY Mean Calculated Annualized Bleed Rate for Treated Target Joint Bleeds |
0.1 | — |
| SECONDARY Median Calculated Annualized Bleed Rate for Treated Target Joint Bleeds |
0.0 | — |
| SECONDARY Model-Based Annualized Bleed Rate for Treated Spontaneous Bleeds |
0.2 | — |
| SECONDARY Mean Calculated Annualized Bleed Rate for Treated Spontaneous Bleeds |
0.3 | — |
| SECONDARY Median Calculated Annualized Bleed Rate for Treated Spontaneous Bleeds |
0.0 | — |
| SECONDARY CATCH Questionnaire for Adult Participants: Change From Baseline in the Daily Activity Risk Perception and Impact Domain Scores Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Adult Participants: Change From Baseline in the Social Activity Risk Perception and Impact Domain Scores Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Adult Participants: Change From Baseline in the Recreational Activity Risk Perception and Impact Domain Scores Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Adult Participants: Change From Baseline in the Work Impact Domain Score Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Adult Participants: Change From Baseline in the Preoccupation Domain Score Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Adult Participants: Change From Baseline in the Treatment Burden Domain Score Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain Associated With a Bleed Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain in Target Joints Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain at Its Worst Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain at Its Least Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain on Average Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Daily Activity Risk Perception and Impact Domain Score Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Social Activity Risk Perception and Impact Domain Score Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Recreational Activity Risk Perception and Impact Domain Score Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Pediatric Participants: Change From Baseline in the School Impact Domain Score Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Preoccupation Domain Score Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Treatment Burden Domain Score Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Pediatric Participants: Number of Participants by Responses to Their Level of Pain Associated With a Bleed Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Pediatric Participants: Number of Participants by Responses to Their Level of Pain at Its Worst Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Caregivers: Change From Baseline in the Preoccupation Domain Score Over Time |
— | — |
| SECONDARY CATCH Questionnaire for Caregivers: Change From Baseline in the Treatment Burden Domain Score Over Time |
— | — |
| SECONDARY Percentage of Participants Who Prefer Emicizumab SC Treatment, Their Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Week 17 |
96.2; 1.9; 1.9 | — |
| SECONDARY Percentage of Caregivers Who Prefer Emicizumab SC Treatment, Their Child's Previous Hemophilia IV Treatment, or Have No Preference, as Assessed Through Use of the Emicizumab Preference Survey at Week 17 |
85.7; 3.6; 10.7 | — |
| SECONDARY Hemophilia Joint Health Scores Over Time |
— | — |
| SECONDARY Change From Baseline in Mean Daily Peak Activity Duration Over Time |
130; 168; 108; -2; -4; -1 | — |
| SECONDARY Change From Baseline in Mean Daily Step Count Over Time |
6441; 6755; 6263; 44; -18; 87 | — |
| SECONDARY Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the MBQ Total Score Over Time |
— | — |
| SECONDARY Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the Heaviness Subscale Score Over Time |
— | — |
| SECONDARY Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the Quality of Life Subscale Score Over Time |
— | — |
| SECONDARY Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the Irregularity Subscale Score Over Time |
— | — |
| SECONDARY Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the Pain Subscale Score Over Time |
— | — |
| SECONDARY Menstruation Diary With the Pictorial Blood Assessment Chart (PBAC) for Female Participants of Childbearing Potential: PBAC Scores Over Time |
— | — |
| SECONDARY Number of Participants With at Least One Adverse Event by Severity, According to the World Health Organization (WHO) Toxicity Grading Scale |
— | — |
| SECONDARY Number of Participants With Adverse Events Leading to Study Drug Discontinuation |
— | — |
| SECONDARY Number of Participants With at Least One Thromboembolic Event |
— | — |
| SECONDARY Number of Participants With at Least One Event of Thrombotic Microangiopathy |
— | — |
| SECONDARY Number of Participants With at Least One Injection-Site Reaction by Severity, According to the WHO Toxicity Grading Scale |
— | — |
| SECONDARY Number of Participants With at Least One Severe Hypersensitivity, Anaphylaxis, and Anaphylactoid Event |
— | — |
| SECONDARY Number of Participants With at Least One Laboratory Abnormality |
— | — |
| SECONDARY Change From Baseline in Respiratory Rate Over Time |
— | — |
| SECONDARY Change From Baseline in Pulse Rate Over Time |
— | — |
| SECONDARY Change From Baseline in Body Temperature Over Time |
— | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure Over Time |
— | — |
| SECONDARY Change From Baseline in Diastolic Blood Pressure Over Time |
— | — |
| SECONDARY Change From Baseline in Electrocardiogram (ECG) Parameters Over Time: QT, QTcB, QTcF, RR, PR, and QRS Intervals |
— | — |
| SECONDARY Change From Baseline in Heart Rate Over Time, as Measured by Electrocardiogram (ECG) |
— | — |
| SECONDARY Plasma Trough Concentration (Ctrough) of Emicizumab Over Time |
— | — |
| SECONDARY Number of Participants With Anti-Drug Antibodies Against Emicizumab at Baseline and Post-Baseline |
— | — |
| SECONDARY Number of Participants Who Develop Anti-FVIII Inhibitors Over Time |
— | — |
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).
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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)
Data sourced from ClinicalTrials.gov (NCT04158648). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.