Primary objective: To investigate the safety of Mim8 prophylaxis in children with haemophilia A with or without FVIII inhibitors.Secondary objectives• To investigate the efficacy of Mim8 prophylaxis in children with haemophilia A with or without…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Number of treatment emergent adverse events from treatment initiation to
follow-up visit (week 0 to week 72)
Secondary outcome
• Number of treated bleeds from treatment initiation to end of treatment (week
0 to week 52)
• Number of treated spontaneous bleeds from treatment initiation to end of
treatment (week 0 to week 52)
• Number of treated traumatic bleeds from treatment initiation to end of
treatment (week 0 to week 52)
• Number of treated joint bleeds from treatment initiation to end of treatment
(week 0 to week 52)
• Number of treated target joint bleeds from treatment initiation to end of
treatment (week 0 to week 52)
• Number of injection site reactions from treatment initiation to end of
treatment (week 0 to week 52)
• Consumption of factor product per bleed treatment from run-in initiation to
end of treatment (week -26 to week 52)
• Occurrence of anti-Mim8 antibodies from treatment initiation to end of
treatment (week 0 to week 52)
• Mim8 plasma concentration from treatment initiation to end of treatment (week
0 to week 52)
• Change in physical function domain of PEDS-QL Generic Core Scales from
treatment initiation to end of treatment (week 0 to week 52)
• Treatment preference for Mim8 versus previous treatment using Caregiver
H-PPQ, once during treatment (week 26)
• Change in patients* treatment burden using the Hemo-TEM from treatment
initiation to end of treatment (week 0 to week 52)
Background summary
Mim8 has been evaluated in a nonclinical programme comprising PK, toxicology,
efficacy and safety pharmacology. Collectively, the nonclinical safety studies
support progression of Mim8 in clinical development.
The FRONTIER1 First Human Dose (FHD) study, administering single ascending
doses (SAD) to healthy participants followed by multiple ascending doses (MAD)
to participants with haemophilia A (NN7769-4513), was initiated in January 2020
and is ongoing. Therefore, no clinical results are available now. Before
initiating the FRONTIER3 study, a safety and PK/PD summary of the available SAD
and MAD data from the FRONTIER1 study will be prepared. This summary will be
submitted to regulatory authorities, if and as required. No risks have been
identified.
Study objective
Primary objective:
To investigate the safety of Mim8 prophylaxis in children with haemophilia A
with or without FVIII inhibitors.
Secondary objectives
• To investigate the efficacy of Mim8 prophylaxis in children with haemophilia
A with or without FVIII inhibitors.
• To evaluate the consumption of coagulation factor replacement product per
bleed treatment (number of injections) with Mim8 prophylaxis in children with
haemophilia A with or without FVIII inhibitors.
• To evaluate the development of anti-Mim8 antibodies with Mim8 prophylaxis in
children with haemophilia A with or without FVIII inhibitors.
• To investigate exposure of Mim8 after once-weekly and once-monthly
subcutaneous dosing in children with haemophilia A with or without FVIII
inhibitors.
• To evaluate treatment burden with Mim8 prophylaxis in children with
haemophilia A with or without FVIII inhibitors, as reported by their caregivers.
• To investigate treatment preference among caregivers of previously treated
children with haemophilia A with or without FVIII inhibitors.
• To evaluate aspects of physical functioning with Mim8 prophylaxis in children
with haemophilia A with or without FVIII inhibitors.
Study design
This is a prospective, multinational, multicentre, open label, non-controlled
and one-arm phase 3 study with no randomisation. The treatment period will be
52 weeks. The study includes a run-in period of at least 26 weeks duration for
participants previously treated on prophylaxis. There is no run-in period for
previously untreated patients (PUPs) and participants on immune tolerance
induction (ITI). The run-in period is optional for participants treated on
demand.
The treatment period is composed of a part 1 and part 2 with 26 weeks of
once-weekly treatment (part 1) followed by 26 weeks of once-weekly or
once-monthly treatment (part 2). For part 2, the participant and
parent(s)/caregiver(s) will be able to choose either weekly or monthly dosing
frequency.
Intervention
Subcutaneous injections of Mim8.
Study burden and risks
Based on the findings from nonclinical studies, on the identified potential
risks described in the protocol, and the possible clinical benefit in
participants with haemophilia A with or without FVIII inhibitors, it is
evaluated that the anticipated benefits outweigh the potential risks of Mim8 in
this phase 3 study. The clinical study may only be conducted (in minors) if it
subjects the person concerned to as little burden, and other foreseeable risks,
as possible.
Flemingweg 8
Alphen aan den Rijn 2408AV
NL
Flemingweg 8
Alphen aan den Rijn 2408AV
NL
Listed location countries
Age
Inclusion criteria
-Informed consent obtained before any study-related activities. Study-related
activities are any procedures that are carried out as part of the study,
including activities to determine suitability for the study.
- Male and female participants with the diagnosis of congenital haemophilia A
of any severity based on medical records.
- Aged 1*11 years (both inclusive) at the time of signing informed consent.
- For previously treated participants :
a. Participant has been prescribed treatment with FVIII concentrate or
bypassing agent in the
last 26 weeks prior to screening.
b. Participant with endogenous FVIII activity >=1%, based on medical records,
must have at
least 1 treated bleed during the previous 26 weeks before screening for which
factor VIII
concentrate or bypassing agent has been prescribed (No requirements for
participants with
FVIII activity <1%).
- For previously untreated participants :
a. Diagnosis of severe haemophilia A (endogenous FVIII activity < 1%) based on
medical
records.
- Child and parent(s)/caregiver(s) willingness and ability to comply with
scheduled visits and
study procedures, including the completion of diary and patient-reported
outcomes
questionnaires.
Exclusion criteria
- Known or suspected hypersensitivity to study product or related products.
- Previous participation in this study. Participation is defined as signed
informed consent.
- Exposure to non-factor haemostatic products for bleeding prophylaxis within 6
months (or 5 half-lives of the medicinal product, whichever is shorter) prior
to planned first dose, for participants not included in the run-in.
- Known congenital or acquired coagulation disorders other than haemophilia A.
- Other conditions (e.g. autoimmune disease) or laboratory abnormality that may
increase risk of bleeding or thrombosis, as evaluated by the investigator.
- Any disorder, except for conditions associated with haemophilia A, that in
the investigator*s opinion might jeopardise the participant*s safety or
compliance with the protocol.
- Mental incapacity, unwillingness to cooperate or a language barrier
precluding adequate understanding and cooperation.
- Lack of adequate parental/caregiver support to enter accurately and timely
information regarding treatment and bleeding episodes into an (electronic)
diary.
- Previous or current treatment for thromboembolic disease (with the exception
of previous catheter-associated thrombosis for which anti-thrombotic treatment
is not currently ongoing) or signs of thromboembolic disease.
- Major surgery planned to take place after screening.
- Immune tolerance induction planned to take place after treatment initiation.
- Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or
alanine aminotransferase (ALT) >3 times the upper limit of normal combined with
total bilirubin >1.5 times the upper limit of normal measured at screening.
- Serum creatinine above 1.5 x upper limit of normal (ULN), measured at
screening.
- Pregnancy (female participants).
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
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 | EUCTR2020-003467-26-NL |
| CCMO | NL78852.018.21 |