Clinical trial NCT05306418: A Research Study Looking at Mim8 in Children With Haemophilia A With or Without Inhibitors
Official title: Safety, Efficacy and Exposure of Subcutaneously Administered NNC0365-3769 (Mim8) Prophylaxis in Children With Haemophilia A With or Without FVIII Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Haemophilia A With or Without Inhibitors
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2022-04-01
Enrollment: 70
Sex: ALL
Minimum age (years): 1
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is looking at how Mim8 works compared to other medicines in children with haemophilia A, who either have inhibitors or do not have inhibitors.

Mim8 is a new medicine that will be used for prevention of bleeds. Mim8 will be injected with a thin needle into the skin. The study will last for about 54-98 weeks, from screening to follow-up visit, In case the participant experiences bleeds, these can be treated with additional haemostatic medicine as agreed with the study doctor.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. Male and female participants with the diagnosis of congenital haemophilia A of any severity based on medical records.
3. Aged 1-11 years (both inclusive) at the time of signing informed consent.
4. For previously treated participants :

   1. Participant has been prescribed treatment with FVIII concentrate or bypassing agent in the last 26 weeks prior to screening.
   2. Participants with endogenous FVIII activity greater than or equal to 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 below 1%).
5. For previously untreated participants:

   a. Diagnosis of severe haemophilia A (endogenous FVIII activity below 1%) based on medical records.
6. Child and parent/caregiver willingness and ability to comply with scheduled visits and study procedures, including the completion of diary and patient-reported outcomes questionnaires.( For China mainland; assessed at the investigator's discretion unless otherwise stated.)

Exclusion criteria:

1. Known or suspected hypersensitivity to trial product or related products.(For China mainland; assessed at the investigator's discretion unless otherwise stated.)
2. Previous participation in this study. Participation is defined as signed informed consent.
3. Participation (i.e., signed informed consent) in any interventional clinical study with receipt of last dose within 6 months (or 5 half-lives of the investigational medicinal product, whichever is shorter) before planned randomisation.
4. Exposure to non-factor haemostatic products for bleeding prophylaxis within 6 months (or 5 half-lives of the medicinal product, whichever is shorter) before planned randomisation, for participants not included in the run-in.
5. Known congenital or acquired coagulation disorders other than haemophilia A.
6. Other conditions (e.g. autoimmune disease) or laboratory abnormality that may increase risk of bleeding or thrombosis, as evaluated by the investigator.(For China mainland; assessed at the investigator's discretion unless otherwise stated.)
7. 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.(For China mainland; assessed at the investigator's discretion unless otherwise stated.)
8. Mental incapacity, unwillingness to cooperate or a language barrier precluding adequate understanding and cooperation.(For China mainland; assessed at the investigator's discretion unless otherwise stated.)
9. Lack of adequate parental/caregiver support to enter accurately and timely information regarding treatment and bleeding episodes into an (electronic) diary.(For China mainland; assessed at the investigator's discretion unless otherwise stated.)
10. 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.
11. Major surgery planned to take place after screening.(For China mainland; assessed at the investigator's discretion unless otherwise stated.)
12. Immune tolerance induction planned to take place after treatment initiation.(For China mainland; assessed at the investigator's discretion unless otherwise stated.)
13. Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 3 times the upper limit of normal combined with total bilirubin greater than 1.5 times the upper limit of normal measured at screening.
14. Serum creatinine above 1.5 x upper limit of normal (ULN), measured at screening.
15. Pregnancy (female participants).(Will be assessed at investigator's discretion, according to suspicion of pregnancy.)

Primary outcomes:
measure: Number of treatment emergent adverse events
timeFrame: From treatment initiation to follow up visit (week 0 to week 72)
Secondary outcomes:
measure: Number of treated bleeds
timeFrame: From treatment initiation to end of treatment (week 0 to week 52)
measure: Number of treated spontaneous bleeds
timeFrame: From treatment initiation to end of treatment (week 0 to week 52)
measure: Number of treated traumatic bleeds
timeFrame: From treatment initiation to end of treatment (week 0 to week 52)
measure: Number of treated joint bleeds
timeFrame: From treatment initiation to end of treatment (week 0 to week 52)
measure: Number of treated target joint bleeds
timeFrame: From treatment initiation to end of treatment (week 0 to week 52)
measure: Number of injection site reactions
timeFrame: From treatment initiation to end of treatment (week 0 to week 52)
measure: Consumption of factor product per bleed treatment (number of injections)
timeFrame: From run-in initiation to end of treatment (week -26 to week 52)
measure: Occurrence of anti-Mim8 antibodies
timeFrame: From treatment initiation to end of treatment (week 0 to week 52)
measure: Mim8 plasma concentration
timeFrame: From treatment initiation to end of treatment (week 0 to week 52)
measure: Change in physical function domain of PEDS QL (Paediatric Quality of Life inventory) Generic Core Scales
timeFrame: From treatment initiation to end of treatment (week 0 to week 52)
measure: Treatment preference for Mim8 versus previous treatment using Caregiver H PPQ (Caregiver Haemophilia Patient Preference )
timeFrame: Once during treatment (week 26)
measure: Change in participants' treatment burden using the Hemo TEM (Haemophilia treatment experience measure)
timeFrame: From treatment initiation to end of treatment (week 0 to week 52)
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa_Iowa City
state: Iowa
city: Cleveland
country: United States
facility: Univ Hosp Cleveland Med Ctr
state: Ohio
city: Hershey
country: United States
facility: Penn State MS Hershey Med Ctr
state: Pennsylvania
city: Philadelphia
country: United States
facility: St Christopher Hosp for Child
state: Pennsylvania
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Beijing
country: China
facility: Beijing Children's Hospital，Capital Medical University
state: Beijing
city: Guangzhou
country: China
facility: Haemotology, Nanfang Hospital, Southern Medical University
state: Guangdong
city: Chengdu
country: China
facility: Chengdu Women's and Children's central hospital
state: Sichuan
city: Tianjin
country: China
facility: Institute of hematology and Blood Diseases Hospital, Tianjin-Hematology
state: Tianjin
city: Hangzhou
country: China
facility: Children's Hospital, Zhejiang University school of medicine
state: Zhejiang
city: Mumbai
country: India
facility: Seth GS Medical College & KEM Hospital
state: Maharashtra
city: Pune
country: India
facility: Sahyadri Super Speciality Hospital
state: Maharashtra
city: Jaipur
country: India
facility: J K Lon Hospital
state: Rajasthan
city: Noida
country: India
facility: Post Graduate Institute of Child Health
state: Uttar Pradesh
city: Tel-Hashomer
country: Israel
facility: Sheba MC The Israeli National Hemophilia Center
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Ges
city: Gunma
country: Japan
facility: Ota Memorial Hospital_Pediatrics
city: Daejeon
country: Korea, Republic of
facility: Daejeon Eulji Medical Center, Eulji University
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego
state: Dolnoslaskie
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Central - Hospital Dona Estefânia
city: Parktown, Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: Esplugues Llobregat
country: Spain
facility: Hospital Sant Joan de Déu
city: Luzern 16
country: Switzerland
facility: Pädiatrische Onkologie-Hämatologie
city: Taipei
country: Taiwan
facility: NTU Hospital - Children and Women Hospital
city: Cardiff
country: United Kingdom
facility: Arthur Bloom Haemophilia Centre
city: London
country: United Kingdom
facility: St Thomas' Hospital
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: