Clinical Trial Results:
Safety, efficacy and exposure of subcutaneously administered NNC0365-3769 (Mim8) prophylaxis in children with haemophilia A with or without FVIII inhibitors
Summary
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EudraCT number |
2020-003467-26 |
Trial protocol |
NL PL IT ES PT LT |
Global end of trial date |
13 Nov 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
28 May 2025
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First version publication date |
28 May 2025
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NN7769-4516
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05306418 | ||
WHO universal trial number (UTN) |
U1111-1255-1540 | ||
Other trial identifiers |
Japanese trial registration number: jRCT2031220670 | ||
Sponsors
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Sponsor organisation name |
Novo Nordisk A/S
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Sponsor organisation address |
Novo Allé, Bagsvaerd, Denmark, 2880
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Public contact |
Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Scientific contact |
Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-002762-PIP02-02 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
07 Jan 2025
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Nov 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To investigate the safety of Mim8 prophylaxis in children with haemophilia A with or without coagulation factor VIII (FVIII) inhibitors.
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Protection of trial subjects |
This study was conducted in accordance with the protocol and consensus ethical principles derived from international guidelines including the Declaration of Helsinki, applicable International Council for Harmonization (ICH) Good Clinical Practice guidelines, and other applicable laws and regulations.
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Background therapy |
The products/treatment used for bleeds and surgery and prophylactic treatment during run-in period, treatment period and the follow-up period were regarded as non-investigational medicinal products (non-IMPs) in this trial. Prophylactic use of standard and extended FVIII products could continue for 1 week after Mim8 loading dose. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
04 Apr 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Canada: 2
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Country: Number of subjects enrolled |
China: 10
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Country: Number of subjects enrolled |
India: 9
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Country: Number of subjects enrolled |
Israel: 2
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Country: Number of subjects enrolled |
Japan: 1
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Country: Number of subjects enrolled |
Italy: 2
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Country: Number of subjects enrolled |
Netherlands: 1
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Country: Number of subjects enrolled |
Poland: 9
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Country: Number of subjects enrolled |
Portugal: 3
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Country: Number of subjects enrolled |
South Africa: 7
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Country: Number of subjects enrolled |
Korea, Republic of: 9
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Country: Number of subjects enrolled |
Spain: 3
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Country: Number of subjects enrolled |
Switzerland: 1
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Country: Number of subjects enrolled |
Taiwan: 2
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Country: Number of subjects enrolled |
United Kingdom: 4
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Country: Number of subjects enrolled |
United States: 6
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Worldwide total number of subjects |
71
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EEA total number of subjects |
18
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
10
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Children (2-11 years) |
61
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 29 sites that recruited subjects in Canada, China, India, Israel, Italy, Japan, Netherlands, Poland, Portugal, South Africa, South Korea, Spain, Switzerland, Taiwan, United Kingdom and United States. | |||||||||||||||
Pre-assignment
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Screening details |
Study included run-in period of at least 26 weeks for children previously treated on prophylaxis (PPX) which was followed by 52-week treatment period with part 1 + part 2, where all subjects received Mim8 and 21-week follow-up period unless the subject or parent(s)/caregiver(s) wanted to transfer to open-label extension study NN7769-4532. | |||||||||||||||
Period 1
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Period 1 title |
Treatment Period - Part 1
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Part 1: Mim8 Once Weekly - Subjects 1-5 years | |||||||||||||||
Arm description |
Subjects aged 1-5 years subcutaneously received Mim8 once weekly based on their weight band until week-26 in part 1. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Mim8
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Investigational medicinal product code |
NNC0365 -3769 B
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
A loading dose was administered once followed by once weekly maintenance doses in part 1. Loading doses were administered by 1 or 2 injections, using 1 or 2 cartridges of study intervention. Maintenance doses were administered by 1 injection using 1 cartridge of study intervention. 0.8 milliliter (mL) of study intervention was administered per injection. Dose amount was based on weight band of subject, whether it was a loading or maintenance dose, and the frequency of dosing: total loading dose (9.0 milligrams [mg] for less than 15 kilograms (kg), 24.0 mg for equals 15 kg - less than 45 kg and 55.0 mg for greater than equals 45 kg); total maintenance dose (1.6 mg for less than 15 kg, 4.0 mg for equals 15 kg - less than 45 kg and 9.0 mg greater than equals 45 kg).
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Arm title
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Part 1: Mim8 Once Weekly - Subjects 6-11 years | |||||||||||||||
Arm description |
Subjects aged 6-11 years subcutaneously received Mim8 once weekly subcutaneously based on their weight band until week-26 in part 1. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Mim8
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Investigational medicinal product code |
NNC0365 -3769 B
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
A loading dose was administered once followed by once weekly maintenance doses in part 1. Loading doses were administered by 1 or 2 injections, using 1 or 2 cartridges of study intervention. Maintenance doses were administered by 1 injection using 1 cartridge of study intervention. 0.8 milliliter (mL) of study intervention was administered per injection. Dose amount was based on weight band of subject, whether it was a loading or maintenance dose, and the frequency of dosing: total loading dose (9.0 milligrams [mg] for less than 15 kilograms (kg), 24.0 mg for equals 15 kg - less than 45 kg and 55.0 mg for greater than equals 45 kg); total maintenance dose (1.6 mg for less than 15 kg, 4.0 mg for equals 15 kg - less than 45 kg and 9.0 mg greater than equals 45 kg).
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The total of 71 subjects enrolled in the study. Out of 71 subjects, 1 subject withdrew during run-in period. Hence, data are reported for 70 participants. |
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Period 2
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Period 2 title |
Treatment Period - Part 2
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Part 2: Mim8 Once Weekly - Subjects 1-5 years | |||||||||||||||
Arm description |
Subjects aged 1-5 years from part 1, decided at week-26 to continue on subcutaneously Mim8 once weekly (dose amount based on their weight band) until week-52 in part 2. The part 2 treatment period was followed by a 21-week follow-up period for all subjects unless the subjects or the parent(s)/caregiver(s) wanted to transfer to the open-label extension study NN7769-4532. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Mim8
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Investigational medicinal product code |
NNC0365 -3769 B
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Doses were administered once weekly in part 2. Doses were administered by 1 injection using 1 cartridge of study intervention. 0.8 mL of study intervention was administered per injection. Dose amount was based on weight band of subject, total dose (1.6 mg for less than 15 kg, 4.0 mg for equals 15 kg - less than 45 kg and 9.0 mg greater than equals 45 kg).
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Arm title
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Part 2: Mim8 Once Weekly - Subjects 6-11 years | |||||||||||||||
Arm description |
Subjects aged 6-11 years from part 1, decided at week-26 to continue on subcutaneously Mim8 once weekly (dose amount based on their weight band) until week-52 in part 2. The part 2 treatment period was followed by a 21-week follow-up period for all subjects unless the subjects or the parent(s)/caregiver(s) wanted to transfer to the open-label extension study NN7769-4532. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Mim8
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Investigational medicinal product code |
NNC0365 -3769 B
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Doses were administered once weekly in part 2. Doses were administered by 1 injection using 1 cartridge of study intervention. 0.8 mL of study intervention was administered per injection. Dose amount was based on weight band of subject, total dose (1.6 mg for less than 15 kg, 4.0 mg for equals 15 kg - less than 45 kg and 9.0 mg greater than equals 45 kg).
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Arm title
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Part 2: Mim8 Once Monthly - Subjects 1-5 years | |||||||||||||||
Arm description |
Subjects aged 1-5 years from part 1, decided at week-26 to switch to subcutaneously Mim8 once monthly (dose amount based on their weight band) until week-52 in part 2. The part 2 treatment period was followed by a 21-week follow-up period for all subjects unless the subjects or the parent(s)/caregiver(s) wanted to transfer to the open-label extension study NN7769-4532. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Mim8
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Investigational medicinal product code |
NNC0365 -3769 B
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Doses were administered once monthly in part 2. Doses were administered by 1 injection using 1 cartridge of study intervention. 0.8 mL of study intervention was administered per injection. Dose amount was based on weight band of subject, total dose (9.0 mg for less than 15 kg, 20.0 mg for equals 15 kg - less than 45 kg and 46.0 mg greater than equals 45 kg).
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Arm title
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Part 2: Mim8 Once Monthly - Subjects 6-11 years | |||||||||||||||
Arm description |
Subjects aged 6-11 years from part 1, decided at week-26 to switch to subcutaneously Mim8 once monthly (dose amount based on their weight band) until week-52 in part 2. The part 2 treatment period was followed by a 21-week follow-up period for all subjects unless the subjects or the parent(s)/caregiver(s) wanted to transfer to the open-label extension study NN7769-4532. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Mim8
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Investigational medicinal product code |
NNC0365 -3769 B
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Doses were administered once monthly in part 2. Doses were administered by 1 injection using 1 cartridge of study intervention. 0.8 mL of study intervention was administered per injection. Dose amount was based on weight band of subject, total dose (9.0 mg for less than 15 kg, 20.0 mg for equals 15 kg - less than 45 kg and 46.0 mg greater than equals 45 kg).
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Baseline characteristics reporting groups
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Reporting group title |
Part 1: Mim8 Once Weekly - Subjects 1-5 years
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Reporting group description |
Subjects aged 1-5 years subcutaneously received Mim8 once weekly based on their weight band until week-26 in part 1. | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part 1: Mim8 Once Weekly - Subjects 6-11 years
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Reporting group description |
Subjects aged 6-11 years subcutaneously received Mim8 once weekly subcutaneously based on their weight band until week-26 in part 1. | ||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Part 1: Mim8 Once Weekly - Subjects 1-5 years
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Reporting group description |
Subjects aged 1-5 years subcutaneously received Mim8 once weekly based on their weight band until week-26 in part 1. | ||
Reporting group title |
Part 1: Mim8 Once Weekly - Subjects 6-11 years
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Reporting group description |
Subjects aged 6-11 years subcutaneously received Mim8 once weekly subcutaneously based on their weight band until week-26 in part 1. | ||
Reporting group title |
Part 2: Mim8 Once Weekly - Subjects 1-5 years
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Reporting group description |
Subjects aged 1-5 years from part 1, decided at week-26 to continue on subcutaneously Mim8 once weekly (dose amount based on their weight band) until week-52 in part 2. The part 2 treatment period was followed by a 21-week follow-up period for all subjects unless the subjects or the parent(s)/caregiver(s) wanted to transfer to the open-label extension study NN7769-4532. | ||
Reporting group title |
Part 2: Mim8 Once Weekly - Subjects 6-11 years
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Reporting group description |
Subjects aged 6-11 years from part 1, decided at week-26 to continue on subcutaneously Mim8 once weekly (dose amount based on their weight band) until week-52 in part 2. The part 2 treatment period was followed by a 21-week follow-up period for all subjects unless the subjects or the parent(s)/caregiver(s) wanted to transfer to the open-label extension study NN7769-4532. | ||
Reporting group title |
Part 2: Mim8 Once Monthly - Subjects 1-5 years
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Reporting group description |
Subjects aged 1-5 years from part 1, decided at week-26 to switch to subcutaneously Mim8 once monthly (dose amount based on their weight band) until week-52 in part 2. The part 2 treatment period was followed by a 21-week follow-up period for all subjects unless the subjects or the parent(s)/caregiver(s) wanted to transfer to the open-label extension study NN7769-4532. | ||
Reporting group title |
Part 2: Mim8 Once Monthly - Subjects 6-11 years
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Reporting group description |
Subjects aged 6-11 years from part 1, decided at week-26 to switch to subcutaneously Mim8 once monthly (dose amount based on their weight band) until week-52 in part 2. The part 2 treatment period was followed by a 21-week follow-up period for all subjects unless the subjects or the parent(s)/caregiver(s) wanted to transfer to the open-label extension study NN7769-4532. | ||
Subject analysis set title |
Part 1+2: Mim8 Once Weekly - Subjects 1-5 years
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects aged 1-5 years subcutaneously received Mim8 once weekly until week-26 in part 1. For the part 2, a subgroup of patients decided at week-26 to continue on Mim8 once weekly until week-52 in part 2. The part 2 treatment period was followed by a 21-week follow-up period for all subjects unless the subjects or the parent(s)/caregiver(s) wanted to transfer to the open-label extension study NN7769-4532.
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Subject analysis set title |
Part 1+2: Mim8 Once Weekly - Subjects 6-11 years
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects aged 6-11 years subcutaneously received Mim8 once weekly until week-26 in part 1. For the part 2, a subgroup of patients decided at week-26 to continue on Mim8 once weekly until week-52 in part 2. The part 2 treatment period was followed by a 21-week follow-up period for all subjects unless the subjects or the parent(s)/caregiver(s) wanted to transfer to the open-label extension study NN7769-4532.
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Subject analysis set title |
Run-in: Previous PPX + Previous On Demand Subjects 1-5 years
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects aged 1-5 years previously treated on prophylaxis (standard/extended half-life FVIII or bypassing agent) or on demand participated in run-in period.
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Subject analysis set title |
Run-in: Previous PPX + Previous On Demand Subjects 6-11 years
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects aged 6-11 years previously treated on prophylaxis (standard/extended half-life FVIII or bypassing agent) or on demand participated in run-in period.
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End point title |
Number of treatment emergent adverse events (TEAEs) [1] | |||||||||||||||
End point description |
AE is any untoward medical occurrence in a subject that is temporally associated with the use of an IMP, whether or not considered related to IMP. Number of TEAEs is presented. AEs were evaluated based on data from on-treatment period which is given as time period in which subject was exposed to trial product and started at the date of first dose of product and ended at the first date of any of the following: end of treatment visit if they enrolled in the study NN7769-4532 or follow-up visit and last date on trial product +21 weeks. Safety analysis set (SAS) included all subjects exposed to at least 1 dose of trial product and were analysed according to treatment they actually received. As defined in protocol section 9, analysis was planned to be performed for once weekly and once monthly treatment regimens. Hence, all of subjects during part 1 as well as that decided to continue on Mim8 once weekly in part 2 are combined and represented in part 1+2 once weekly reporting group.
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End point type |
Primary
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End point timeframe |
From treatment initiation to follow up visit (week 0 to week 72)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary endpoint investigated safety and was analysed using descriptive statistics, and thus no statistical analysis was performed. |
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No statistical analyses for this end point |
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End point title |
Number of treated bleeds | |||||||||||||||
End point description |
A bleed is considered treated if a coagulation factor product is administered to stop the bleed. Number of treated bleeds are presented. The endpoint was evaluated based on in-study period. The in-study period started at the first dose of Mim8 or screening (for run-in) and ended at the end of treatment period or discontinuation of Mim8. Analysis population (full analysis set [FAS]) included all subjects exposed to at least 1 dose of trial product. Subjects were analysed according to the treatment they actually received. As defined in protocol section 9, analysis was planned to be performed for once weekly and once monthly treatment regimens. Hence, all of subjects during part 1 as well as that decided to continue on Mim8 once weekly in part 2 are combined and represented in part 1+2 once weekly reporting group.
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End point type |
Secondary
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End point timeframe |
From treatment initiation to end of treatment (week 0 to week 52)
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No statistical analyses for this end point |
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End point title |
Number of treated spontaneous bleeds | |||||||||||||||
End point description |
A bleed is considered treated if a coagulation factor product is administered to stop the bleed. A spontaneous bleed refers bleeding instance that occur without a clear cause or not linked to a specific, known event or activity. Number of treated spontaneous bleeds are presented. The endpoint was evaluated based on in-study period. The in-study period started at the first dose of Mim8 or screening (for run-in) and ended at the end of treatment period or discontinuation of Mim8. FAS included all subjects exposed to at least 1 dose of trial product. Subjects were analysed according to the treatment they actually received. As defined in protocol section 9, analysis was planned to be performed for once weekly and once monthly treatment regimens. Hence, all of subjects during part 1 as well as that decided to continue on Mim8 once weekly in part 2 are combined and represented in part 1+2 once weekly reporting group.
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End point type |
Secondary
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End point timeframe |
From treatment initiation to end of treatment (week 0 to week 52)
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No statistical analyses for this end point |
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End point title |
Number of treated joint bleeds | |||||||||||||||
End point description |
A bleed is considered treated if a coagulation factor product is administered to stop the bleed. A joint bleed refers bleeding instance that is caused in joints. Number of treated joints bleeds are presented. The endpoint was evaluated based on in-study period. The in-study period started at the first dose of Mim8 or screening (for run-in) and ended at the end of treatment period or discontinuation of Mim8. FAS included all subjects exposed to at least 1 dose of trial product. Subjects were analysed according to the treatment they actually received. As defined in protocol section 9, analysis was planned to be performed for once weekly and once monthly treatment regimens. Hence, all of subjects during part 1 as well as that decided to continue on Mim8 once weekly in part 2 are combined and represented in part 1+2 once weekly reporting group.
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End point type |
Secondary
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End point timeframe |
From treatment initiation to end of treatment (week 0 to week 52)
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No statistical analyses for this end point |
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End point title |
Number of treated traumatic bleeds | |||||||||||||||
End point description |
A bleed is considered treated if a coagulation factor product is administered to stop the bleed. A traumatic bleed refers bleeding instance that is caused by a specific, known event or activity (e.g. injury or exercise). Number of treated traumatic bleeds are presented. The endpoint was evaluated based on in-study period. The in-study period started at the first dose of Mim8 or screening (for run-in) and ended at the end of treatment period or discontinuation of Mim8. FAS included all subjects exposed to at least 1 dose of trial product. Subjects were analysed according to the treatment they actually received. As defined in protocol section 9, analysis was planned to be performed for once weekly and once monthly treatment regimens. Hence, all of subjects during part 1 as well as that decided to continue on Mim8 once weekly in part 2 are combined and represented in part 1+2 once weekly reporting group.
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End point type |
Secondary
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End point timeframe |
From treatment initiation to end of treatment (week 0 to week 52)
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No statistical analyses for this end point |
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End point title |
Number of treated target joint bleeds | |||||||||||||||
End point description |
A bleed is considered treated if a coagulation factor product is administered to stop the bleed. A target joint is defined as a joint in which 3 or more spontaneous bleeding episodes have occurred within 6 months before the date of the assessment. Number of treated target joints bleeds are presented. The endpoint was evaluated based on in-study period. The in-study period started at the first dose of Mim8 or screening (for run-in) and ended at the end of treatment period or discontinuation of Mim8. FAS included all subjects exposed to at least 1 dose of trial product. Subjects were analysed according to the treatment they actually received. As defined in protocol section 9, analysis was planned to be performed for once weekly and once monthly treatment regimens. Hence, all of subjects during part 1 as well as that decided to continue on Mim8 once weekly in part 2 are combined and represented in part 1+2 once weekly reporting group.
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End point type |
Secondary
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End point timeframe |
From treatment initiation to end of treatment (week 0 to week 52)
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No statistical analyses for this end point |
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End point title |
Number of injection site reactions | |||||||||||||||
End point description |
Injection site reactions were assessed based on subject feedback and visual inspection of injection site. Number of injection site reactions are presented. Endpoint was evaluated based on data from on-treatment period. The on-treatment period represented the time period in which a subject was considered exposed to trial product and started at the date of first dose of trial product and ended at the first date of any of the following: end of treatment visit if they enrolled in the study NN7769-4532 or the follow-up visit and the last date on trial product + 21 weeks. SAS included all subjects exposed to at least 1 dose of trial product and were analysed according to the treatment they actually received. As defined in protocol section 9, analysis was planned to be performed for once weekly and once monthly treatment regimens. Hence, all of subjects during part 1 as well as that decided to continue on Mim8 once weekly in part 2 are combined and represented in part 1+2 once weekly group.
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End point type |
Secondary
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End point timeframe |
From treatment initiation to end of treatment (week 0 to week 52)
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No statistical analyses for this end point |
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End point title |
Occurrence of anti-Mim8 antibodies | |||||||||||||||
End point description |
Number of subjects with anti-Mim8 antibodies are presented. The endpoint was evaluated based on data from on-treatment period. The on-treatment period represented the time period in which a subject was considered exposed to trial product and started at the date of first dose of trial product and ended at the first date of any of the following: end of treatment visit if they enrolled in the study NN7769-4532 or the follow-up visit and the last date on trial product + 21 weeks. SAS included all subjects exposed to at least 1 dose of trial product. Subjects were analysed according to the treatment they actually received. As defined in protocol section 9, analysis was planned to be performed for once weekly and once monthly treatment regimens. Hence, all of subjects during part 1 as well as that decided to continue on Mim8 once weekly in part 2 are combined and represented in part 1+2 once weekly reporting group.
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End point type |
Secondary
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End point timeframe |
From treatment initiation to end of treatment (week 0 to week 52)
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No statistical analyses for this end point |
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End point title |
Consumption of factor product per bleed treatment (number of injections per bleed) | ||||||||||||||||||||||||||||||||||||
End point description |
Consumption of factor product per bleed treatment was calculated as number of injections used in the time period from the start of bleed to the stop of bleed. The mean number of injections required to stop the bleed is presented. The analysis was based on the total number of bleeds. The endpoint was evaluated based on in-study period. The in-study period starts at the first dose of Mim8 or screening (for run-in) and ends at the end of treatment period or discontinuation of Mim8. For subjects with run-in, the in-study period starts at screening and ends at the end of treatment period or discontinuation of Mim8. FAS included all subjects exposed to at least 1 dose of trial product. Subjects were analysed according to the treatment they actually received.
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End point type |
Secondary
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End point timeframe |
From run-in initiation to end of treatment (week -26 to week 52)
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No statistical analyses for this end point |
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End point title |
Mim8 plasma concentration | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The endpoint was evaluated based on in-study period. The in-study period started at the first dose of Mim8 or screening (for run-in) and ended at the end of treatment period or discontinuation of Mim8. FAS included all subjects exposed to at least 1 dose of trial product. Subjects were analysed according to the treatment they actually received. Here, "n" represents number of subjects who evaluable at specific time point for respective reporting group and "99999" indicates not applicable data point.
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End point type |
Secondary
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End point timeframe |
From treatment initiation to end of treatment (week 0 to week 52)
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No statistical analyses for this end point |
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End point title |
Treatment preference for Mim8 versus previous treatment using Caregiver Haemophilia Patient Preference Questionnaire (Caregiver H-PPQ) | |||||||||||||||||||||||||||
End point description |
The questionnaire assesses "Overall which treatment do you prefer?”, with the response options “current”, “previous” or “no preference”, and "How strong is that preference", with the response options “very strong”, “fairly strong”, and “not very strong”. Percentage of subjects with treatment preference for Mim8 versus previous treatment using caregiver H-PPQ is presented. The caregiver H-PPQ is only relevant for previously treated subjects. The endpoint was evaluated based on in-study period. The in-study period started at the first dose of Mim8 or screening (for run-in) and ended at the end of treatment period or discontinuation of Mim8. FAS included all subjects exposed to at least 1 dose of trial product. Subjects were analysed according to the treatment they actually received. Here, "number of subjects analysed" included subjects who had responded the questionnaire within a 1 day interval and applicable for previously treated subjects at week 26.
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End point type |
Secondary
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End point timeframe |
Once during treatment (week 26)
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No statistical analyses for this end point |
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End point title |
Change in physical function domain of Paediatric Quality of Life inventory (PEDS-QL) Generic Core Scales | ||||||||||||||||||||
End point description |
PedsQL assesses quality of life, including domains like physical functioning. Higher scores indicate better quality of life and physical functioning with range from 0-100. Positive change indicates improvement and negative change indicates worsening. Questionnaire is for 5 to 11 years. Change in PEDS-QL from week 0 to week 52 is presented. Endpoint based on in-study period which started at first dose of Mim8 or screening (for run-in) and ended at end of treatment or discontinuation of Mim8. FAS included subjects exposed to at least 1 dose of trial product and analysed based on treatment they actually received. In protocol section 9, analysis was planned to be performed for once weekly and once monthly treatment regimens. Hence, all of subjects during part 1 as well as that decided to continue on Mim8 once weekly in part 2 are combined and represented in part 1+2 once weekly group. Here, "subject analysed" included responders at week 0 and week 52 and "99999" indicates not applicable.
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End point type |
Secondary
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End point timeframe |
From treatment initiation to end of treatment (week 0 to week 52)
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No statistical analyses for this end point |
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End point title |
Change in subjects’ treatment burden using the Haemophilia treatment experience measure (Hemo TEM) | ||||||||||||||||||||
End point description |
Child Hemo-TEM (caregiver reported) measures treatment burden. Change in subjects’ treatment burden using Hemo TEM from week 0 to week 52 is presented. The score ranges from 0-100 where lower score indicates lower treatment burden. The caregiver H-PPQ is only relevant for previously treated subjects. Endpoint was evaluated based on in-study period. The in-study period started at the first dose of Mim8 or screening (run-in) and ended at the end of treatment period or discontinuation of Mim8. FAS included all subjects exposed to at least 1 dose of trial product. Subjects were analysed according to the treatment they actually received. In protocol section 9, analysis was planned to be performed for once weekly and once monthly treatment regimens. Hence, all of subjects during part 1 as well as that decided to continue on Mim8 once weekly in part 2 are combined and represented in part 1+2 once weekly reporting group. Here, "subject analysed" includes responders at week 0 and week 52.
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End point type |
Secondary
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End point timeframe |
From treatment initiation to end of treatment (week 0 to week 52)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From treatment initiation to follow up visit (week 0 to week 72)
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Adverse event reporting additional description |
Based on on-treatment period - period started at the date of first dose and ended at the first date of any of following: end of treatment if they enrolled in NN7769-4532 or follow-up and last date on trial product +21 weeks. SAS included all subjects exposed to at least 1 dose of trial product and based on treatment they actually received.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.1
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Reporting groups
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Reporting group title |
Part 1+2: Mim8 - Subjects 6-11 years
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Reporting group description |
All subjects aged 6-11 years received subcutaneously Mim8 once weekly in part 1 and part 2 or once weekly in part 1 and once monthly in part 2 from week 0 until week 52. The part 2 treatment period was followed by a 21-week follow-up period for all subjects unless the subjects or the parent(s)/caregiver(s) wanted to transfer to the open-label extension study NN7769-4532. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part 1+2: Mim8 - Subjects 1-5 years
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Reporting group description |
All subjects aged 1-5 years received subcutaneously Mim8 once weekly in part 1 and part 2 or once weekly in part 1 and once monthly in part 2 from week 0 until week 52. The part 2 treatment period was followed by a 21-week follow-up period for all subjects unless the subjects or the parent(s)/caregiver(s) wanted to transfer to the open-label extension study NN7769-4532. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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25 Jun 2021 |
Amended to extend the follow-up period from 16 to 21 weeks after last dose; to clarify inclusion criterion 4 - it will be assessed by checking if the subject had a prescription of FVIII concentrate or bypassing agent; correction to align with the study design, as subjects treated on demand have the option to have a run-in period; Correction to specify that the target joints only need be assessed at week 4; to specify that clinical safety data from the phase 1 study will be summarised before this study will be initiated and that the summary will be submitted to regulatory authorities if and as required. |
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26 Aug 2021 |
Amended to add statement to clarify children under which age
group are allowed for the first 10 subjects to be dosed in the study; in order to describe the involvement of data monitoring committee (DMC) in decisions regarding study and confirmation of the role of DMC in the study. |
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22 Aug 2022 |
Amended to include the dose for subjects based on the multiple ascending dose (MAD) part of study NN7769-4513 and on study NN7769-4882; exclusion criterion updated regarding requirement of participation in any interventional clinical study prior to this study; exclusion criterion updated regarding exposure to non-factor haemostatic products; to comply with section about concomitant medication; updated sections based on interim CTR from study NN7769-4513; to specify an aim to obtain equal distribution of the subjects in the study. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |