| CTRI Number |
CTRI/2023/02/049474 [Registered on: 06/02/2023] Trial Registered Prospectively |
| Last Modified On: |
27/12/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
|
Public Title of Study
|
A research study investigating Mim8 in adults and adolescents with haemophilia A with or without inhibitors |
|
Scientific Title of Study
|
A multinational, open-label, randomised, controlled study to investigate efficacy and safety of NNC0365-3769 (Mim8) in adults and adolescents with haemophilia A with or without inhibitors. |
| Trial Acronym |
Frontier 2 |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 2020-001048-24 |
EudraCT |
| NN7769-4514, Version 9.0 dated 26 Aug 2022 |
Protocol Number |
| U1111-1249-4378 |
UTN |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
|
| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Maya Sharma |
| Designation |
Vice President -Clinical, Medical, Regulatory & Pharmacovigilance. |
| Affiliation |
Novo Nordisk India Pvt Ltd |
| Address |
Novo Nordisk India Private Limited
Nxt Tower - 2, Floor 1 & 2
Embassy Manyata Business Park,
Nagavara Village, Kasaba Hobli,
Bangalore-560045
Karnataka
Novo Nordisk India Private Limited,
Nxt Tower - 2, Floor 1 & 2
Embassy Manyata Business Park,
Nagavara Village, Kasaba Hobli,
Bangalore - 560045.
Bangalore
KARNATAKA
560045
India |
| Phone |
09911497869 |
| Fax |
|
| Email |
yrms@novonordisk.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Dr Maya Sharma |
| Designation |
Vice President -Clinical, Medical, Regulatory & Pharmacovigilance. |
| Affiliation |
Novo Nordisk India Pvt Ltd |
| Address |
Novo Nordisk India Private Limited,
Nxt Tower - 2, Floor 1 & 2
Embassy Manyata Business Park,
Nagavara Village, Kasaba Hobli,
Bangalore - 560045. India
Karnataka
Novo Nordisk India Private Limited,
Nxt Tower - 2, Floor 1 & 2
Embassy Manyata Business Park,
Nagavara Village, Kasaba Hobli,
Bangalore - 560045. India
Bangalore
KARNATAKA
560045
India |
| Phone |
09911497869 |
| Fax |
|
| Email |
yrms@novonordisk.com |
|
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Source of Monetary or Material Support
|
| Novo Nordisk A/S, Novo Allé, 2880 Bagsvaerd Denmark |
|
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Primary Sponsor
|
| Name |
Novo Nordisk AS |
| Address |
Novo Allé, 2880 Bagsvaerd Denmark |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
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Countries of Recruitment
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Malaysia
Mexico
Austria
Belgium
Canada
China
Denmark
France
Germany
India
Ireland
Israel
Italy
Japan
Latvia
Lithuania
Netherlands
Poland
Portugal
Republic of Korea
Romania
Russian Federation
Saudi Arabia
Serbia
South Africa
Spain
Switzerland
Taiwan
Turkey
United Kingdom
United States of America |
|
Sites of Study
|
| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Aby Abraham |
Christian Medical College and Hospital |
Department of Haematology
Christian Medical College and hospital
Vellore
Tamil Nadu
India
Vellore
TAMIL NADU |
04162282352
haemat@cmcvellore.ac.in |
| Dr M Joseph John |
Christian Medical College and Hospital |
Christian Medical
College and Hospital
Haemato-Oncology and
Bone Marrow (Stem
Cell) Transplant Unit
Brown Road
Ludhiana
Punjab
India
Ludhiana
PUNJAB |
8054959525
mjosephjohn@gmail.com |
| Dr Nirmalkumar Ganeshmal Choraria |
Nirmal Hospital Pvt. Ltd. |
Nirmal Hospital Pvt. Ltd., Sagrampura,
Surat, Gujarat 395002, India.
Surat
GUJARAT |
9825142549
drnirmalchoraria@gmail.com |
| Dr Nita Radhakrishnan |
Post Graduate Institute of Child Health |
Department of Paediatric Haematology-oncology, Post Graduate Institute of Child Health, Noida- 201303
Gautam Buddha Nagar
UTTAR PRADESH |
9999041524
nitark@gmail.com |
| Dr Chandrakala S |
Seth GS Medical College and KEM Hospital |
Department of Haematology
Seth GS Medical College and KEM Hospital
Parel
Mumbai
India
Mumbai
MAHARASHTRA |
9699087654
drchandra_s@rediffmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| Ethics Committee- Silver Institution Review Board Office of Research Christian Medical College- Vellore |
Approved |
| Institutional Ethics Committee Christian Medical College and Hospital Christian Medical College-Ludhiana |
Approved |
| Institutional Ethics Committee Super specialty Paediatric Hospital and PGTI SSPHPGTI |
Approved |
| Institutional Ethics Committee-l, Seth GS Medical College and KEM Hospital |
Approved |
| Nirmal Hospital Ethics Committee |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D66||Hereditary factor VIII deficiency, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
NNC0365-3769 (Mim8) |
Dose: TF or a once-weekly dose interval, including the loading dose, the anticipated dose will be within the
range 10–75 mg and for the maintenance dose, within the range 3−20 mg. For a once monthly dose
interval, including the loading dose, the anticipated dose will be within the range 40−180 mg and
for the maintenance dose, within the range 20−80 mg.
Duration:52 Weeks
Frequency: Weekly onece and monthly once
Rout of administration: Subcutaneous |
| Comparator Agent |
Not Applicable |
Not Applicable |
|
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Inclusion Criteria
|
| Age From |
12.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
• 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 or female participants with diagnosis of congenital haemophilia A of any severity based on medical records.
• Participant has been prescribed treatment with factor VIII concentrates or bypassing agent in the last 26 weeks prior to screening.
• Age above or equal to 12 years at the time of signing informed consent.
• Body weight greater than or equal to 30 kg.
• Applicable to participants treated with on-demand/no prophylaxis prior to enrolment: ≥5 bleeds in the last 26 weeks prior to screening visit, for which factor VIII concentrates or bypassing agent has been prescribed.
• Applicable to participants with FVIII activity ≥1% who are on prophylactic treatment: ≥1 bleed in the last 26 weeks prior to screening visit, for which factor VIII concentrates or bypassing agent has been prescribed.
• Willingness and ability to comply with scheduled visits and study procedures, including the completion of diary and patient-reported outcomes questionnaires.
|
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| ExclusionCriteria |
| Details |
1. Previous participation in this study. Participation is defined as signed informed consent.
2. Participation (that is, signed informed consent) in any interventional clinical study with receipt of the last dose within 6 months (or 5 half-lives of the investigational medicinal product, whichever is shorter) before planned randomisation.
3. Exposure to non-factor hemostatic 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.
4. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method. Breast feeding is allowed only during the run-in period.
5. Any disorder, except for conditions associated with hemophilia A, which in the investigators opinion might jeopardise participants safety or compliance with the protocol.
6. Known or suspected hypersensitivity to trial product(s), any constituents of the product or to related products.
7. Receipt of gene therapy at any given time point.
8. Ongoing or planned immune tolerance induction (ITI) therapy.
9. Major surgery planned to take place after screening.
10. Known congenital or acquired coagulation disorders other than hemophilia A.
11. Hepatic dysfunction defined as aspartate aminotransferase (AST) and or alanine aminotransferase (ALT) above 3 times the upper limit combined with total bilirubin above 1.5 times the upper limit measured at screening.
12. Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below or equal to 30 ml per min per 1.73 meter square for serum creatinine measured at screening.
13. Previous or current thromboembolic disease or events (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or risk of thromboembolic disease, as evaluated by investigator.
14. Mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation.
Other conditions (example, autoimmune disease) or laboratory abnormality that may increase risk of bleeding or thrombosis as evaluated by the investigator. |
|
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Method of Generating Random Sequence
|
Computer generated randomization |
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Method of Concealment
|
Centralized |
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Blinding/Masking
|
Open Label |
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Primary Outcome
|
| Outcome |
TimePoints |
To confirm the haemostatic effect of Mim8 as bleeding prophylaxis for adults and adolescents with haemophilia A with or without inhibitors by demonstrating superiority in number of bleeding episodes when treated with Mim8 once-weekly versus no prophylaxis followed by Mim8 once-monthly versus no prophylaxis for participants on no prophylaxis treatment prior to enrolment.
Unit: Count |
Prophylaxis treatment (Arms 3 and 4):
From initiation of run-in (26-52 weeks prior to week 0) to
week 0 and from randomisation (week 0) to end of main
(Week 26) |
|
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Secondary Outcome
|
| Outcome |
TimePoints |
| Occurrence of anti-Mim8 antibodies |
All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of extension (week 52) |
| Number of treated spontaneous bleeds |
No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (Week 26) Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from week 0 to end of main (week 26) |
| Number of injection site reactions |
All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of main (week 26) |
| Number of treated joint bleeds |
No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (Week 26) Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from week 0 to end of main (week 26) |
| Number of treated traumatic bleeds |
No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (Week 26) Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from week 0 to end of main (week 26) |
| Number of target joint bleeds |
No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (Week 26) Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from week 0 to end of main (week 26) |
Consumption of factor product per bleed treatment
(number of injections) |
No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (Week 26) Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from week 0 to end of main (week 26) |
| Change in physical function domain of PEDS-QL |
All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26)
Score points Minimum score per question (best) is equals to 0
Maximum score per question (worst) is equals to 4
Total score for 13 questions: 0 (best) to 92 (worst) |
| Change in patient’s treatment burden using the Hemo-TEM |
All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26)
Score points ranges from 0 is equals to not at all (best) to 4 is equals to extremely (worst) |
Change in patient’s joint pain score using
Joint Pain Rating Scale |
All subjects (Arms 1, 2, 3 and 4):
From randomisation (week 0) to the end of the main part (week 26) |
|
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Target Sample Size
|
Total Sample Size="267"
Sample Size from India="12"
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="0" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
10/02/2023 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
02/12/2021 |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="2"
Months="3"
Days="15" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
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Publication Details
|
none yet |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
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Brief Summary
|
This study is investigating how Mim8 works compared to
other medicines in people with haemophilia A, who either have inhibitors
or do not have inhibitors. Mim8 is a new medicine that will be used for
prevention of bleeding episodes. Mim8 works by replacing the function of
the missing clotting factor VIII (FVIII).
When
and how often participants will receive Mim8 is dependent on their previous
treatment - but is otherwise decided by chance. Mim8 will be injected into a
skinfold on the stomach with a thin needle either once a week or once a month.
The
study will last 54-124 weeks (12-29 months) depending on how long participants
will be followed in run-in before they start treatment and if they continue in
the follow period or transfer to an open label extension study. Participants
will have 12-17 clinic visits. |