Study MO41787 will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab administered at 3 mg/kg Q2W for a period of 52 weeks in previously untreated patients (PUPs) and minimally treated patients (MTPs) at study…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The efficacy objective for this study is to evaluate the efficacy of emicizumab
on the basis of the following endpoints:
- Number of treated bleeds over time (i.e., treated bleed rate)
- Number of all bleeds over time (i.e., all bleed rate)
- Number of treated spontaneous bleeds over time (i.e., treated spontaneous
bleed rate)
- Number of treated joint bleeds over time (i.e., treated joint bleed rate)
- Joint health, as assessed through use of the Hemophilia Joint Health Score
(HJHS) and magnetic resonance imaging (MRI) score of specific joints at
specified timepoints only during the 7-year LTFU period
Secondary outcome
The safety objective for this study is to evaluate the safety of emicizumab on
the basis of the following endpoints:
- Incidence and severity of adverse events, with severity determined according
to
WHO Toxicity Grading Scale (see Appendix 5)
- Incidence of thromboembolic events
- Incidence of thrombotic microangiopathy (TMA)
- Change from baseline in physical examination findings
- Change from baseline in vital signs
- Incidence of laboratory abnormalities
- Incidence and severity of injection-site reactions
- Incidence of adverse events leading to drug discontinuation
- Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events
See protocol section 2 for Pharmacokinetic, biomarker and Immunogenicity
objectives
Background summary
Infant patients with hemophilia A constitute a vulnerable population with high
unmet medical need.
In children, the current standard of care is primary prophylaxis with regular
FVIII infusions (starting from the first joint bleed onward or earlier),
focusing on joint preservation with optimally, no bleeds and the prevention of
long-term consequences such as joint damage. Because of difficulties in venous
access in newborns and infants, replacement therapy often necessitates the
placement of central venous access devices (CVADs). However, long-term CVAD use
requires considerable commitment from caregivers and parents, and serious
complications can occur, including thrombosis, bleeding, mechanical
dysfunction, and most commonly, infection.
The administration of prophylactic factor concentrate at birth is recommended
because it is highly efficacious to prevent bleeds, but the risks of FVIII
inhibitor development from early factor exposure of newborns and infants
remain. The development of FVIII inhibitors represents a challenging and costly
complication of treatment. See part 1 of protocol
Study objective
Study MO41787 will evaluate the efficacy, safety, pharmacokinetics, and
pharmacodynamics of emicizumab administered at 3 mg/kg Q2W for a period of 52
weeks in previously untreated patients (PUPs) and minimally treated patients
(MTPs) at study enrollment from birth to <= 12 months of age with severe
hemophilia A (intrinsic FVIII level < 1%) without FVIII inhibitors. After 1
year of treatment, patients will continue to receive emicizumab (1.5 mg/kg QW,
3 mg/kg Q2W, or 6 mg/kg Q4W) over a 7-year LTFU period, which will evaluate
long-term safety of emicizumab and describe the natural history of these
patients, including the preservation of joint health over time. Study MO41787
is a descriptive study with no formal hypothesis testing. Specific objectives
and corresponding endpoints for the study are outlined in part 2 of the
protocol.
Study design
Study MO41787 is a Phase IIIb, multicenter, open-label, single-arm study of
emicizumab in PUPs and MTPs at study enrollment from birth to * 12 months of
age with severe hemophilia A (intrinsic FVIII level * 1%) without FVIII
inhibitors. The study is designed to evaluate the efficacy, safety,
pharmacokinetics, and pharmacodynamics of emicizumab administered at 3 mg/kg
Q2W for 52 weeks. After 1 year of treatment, patients will
continue to receive emicizumab (1.5 mg/kg QW, 3 mg/kg Q2W or 6 mg/kg Q4W) over
a 7-year LTFU period under this study frame. Study MO41787 is a descriptive
study with no formal hypothesis testing. See part 3 of protocol
Intervention
Emicizumab will be administered at 3 mg/kg Q2W for a period of 52 weeks. After
1 year of treatment, patients will continue to receive emicizumab (1.5 mg/kg
QW, 3 mg/kg Q2W, or 6 mg/kg Q4W) over a 7-year LTFU period
Study burden and risks
The general burden on the patients consists, among other things, of blood
sampling (each visit), visit to the site every week the first 5 weeks, every 4
weeks the first year, and every year the next 7 years. Also the administration
of the study drug (every 2 weeks for the first year, thereafter every week, two
weeks or four weeks). that may lead to various adverse events.
Beneluxlaan 2a
Woerden 3446 GR
NL
Beneluxlaan 2a
Woerden 3446 GR
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria:
* Age from birth to <<= 12 months at time of informed consent
* Body weight ><= 3 kg at time of informed consent
* Mandatory receipt of vitamin K prophylaxis according to local standard
practice
* Diagnosis of severe congenital hemophilia A (intrinsic FVIII level < 1%)
* A negative test for FVIII inhibitor (i.e., < 0.6 Bethesda units [BU]/mL)
locally assessed during the 2-week screening period for all patients
* For PUPs or MTPs, up to 5 days of exposure with hemophilia-related
treatments, such as plasma-derived FVIII, recombinant FVIII, fresh frozen
plasma, cryoprecipitate, or whole blood products
* Documentation of the details of the hemophilia-related treatments received
since birth
* Documentation of the details of the bleeding episodes since birth
* For patients from birth to < 3 months of age at the time of study entry: no
evidence of active ICH, as confirmed by a negative cranial ultrasound at
screening irrespective of delivery mode
* Adequate hematologic, hepatic, and renal function
Exclusion criteria
Exclusion criteria
* Inherited or acquired bleeding disorder other than severe hemophilia A
* Use of systemic immunomodulators (e.g., interferon) at enrollment or planned
use during the study
* Receipt of any of the following:
* An investigational drug to treat or reduce the risk of hemophilic bleeds
within 5 drug-elimination half-lives of last drug administration
* A non-hemophilia-related investigational drug within the last 30 days or 5
drug-elimination half-lives, whichever is shorter
* An investigational drug concurrently
* Current active severe bleed, such as ICH
* Planned surgery during the study
* History of clinically significant hypersensitivity associated with monoclonal
antibody therapies or components of the emicizumab injection
* Previous or current treatment for thromboembolic disease or signs of
thromboembolic disease
* Any hereditary or acquired maternal condition that may predispose the patient
to thrombotic events
* Other diseases (e.g., certain autoimmune diseases) that may increase risk of
bleeding or thrombosis
* Known infection with HIV, hepatitis B virus, or hepatitis C virus
* Serious infection requiring antibiotics or antiviral treatments within 14
days prior to screening
* Concurrent disease, treatment, abnormality in clinical laboratory tests,
vital signs measurements, or physical examination findings that could interfere
with the conduct of the study or that would, in the opinion of the investigator
or Sponsor, preclude the patient*s safe participation in and completion of the
study or interpretation of the study results
* Unwillingness of the parent or caregiver to allow receipt of blood or blood
products, or any standard-of-care treatment for a life-threatening condition
* Any other medical, social, or other condition that may prevent adequate
compliance with the study protocol in the opinion of the investigator
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-001733-12-NL |
| ClinicalTrials.gov | NCT04431726 |
| CCMO | NL75360.056.20 |