Research study to look at how well the drug Concizumab works in your body if you have haemophilia without inhibitors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

15 Jan 2020 → ongoing

Decision date (initial)

2024-02-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2023-506831-13-00

EudraCT number

2018-004891-36

WHO UTN

U1111-1225-9722

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare the effect of concizumab prophylaxis to no prophylaxis (on demand treatment with factor) in reducing the number of bleeding episodes in adult and adolescent patients with haemophilia A without inhibitors.
To compare the effect of concizumab prophylaxis to no prophylaxis (on demand treatment with factor) in reducing the number of bleeding episodes in adult and adolescent patients with haemophilia B without inhibitors.

Secondary objectives 4

1. To compare the effect of concizumab prophylaxis to the patients’ previous prophylaxis treatment in reducing the number of bleeding episodes in adult and adolescent patients with haemophilia A without inhibitors
2. To compare the effect of concizumab prophylaxis to the patients’ previous prophylaxis treatment in reducing the number of bleeding episodes in adult and adolescent patients with haemophilia B without inhibitors
3. To investigate the safety of concizumab prophylaxis in adult and adolescent patients with haemophilia A or B without inhibitors
4. To investigate the PK and PD parameters of concizumab prophylaxis in adult and adolescent patients with haemophilia A or B without inhibitors

Conditions and MedDRA coding

haemophilia A (HA) without inhibitors and haemophilia B (HB) without inhibitors

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Paul-Ehrlich-Institut, Pharmaceuticals And Medical Devices Agency, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002326-PIP04-20

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
2. Male aged ≥12 years at the time of signing informed consent
3. Body weight >25 kg at screening
4. Congenital severe haemophilia A (FVIII < 1%) or moderate/severe B (FIX ≤ 2%).
5. Documented treatment with coagulation factor containing product in the last 24 weeks (not applicable for NN7415-4255 (explorer5) patients enrolled prior to the treatment pause).

Exclusion criteria 14

1. Known or suspected hypersensitivity to any constituent of the trial product or related products
2. Previous participation in this trial. Participation is defined as signed informed consent. However, this is not applicable for patients who were screen failed at Sponsor’s decision due to the treatment pause
3. Participation in any clinical trial of an approved or non-approved investigational medicinal product within 5 half-lives or 30 days from screening, whichever is longer (not applicable for NN7415-4255 patients enrolled prior to the treatment pause).
4. Platelets ≤100x109/L at screening
5. Fibrinogen below laboratory lower normal limit at screening
6. Hepatic dysfunction defined as AST and/or ALT >3 times the upper limit combined with total bilirubin > 1,5 times the upper limit at screening
7. Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) ≤30 ml/min/1.73 m2 for serum creatinine measured at screening
8. Known inherited or acquired coagulation disorder other than congenital haemophilia
9. History of thromboembolic disease. Current clinical signs of, or treatment for thromboembolic disease. Patients who in the judgement of the investigator are considered at high risk of thromboembolic events
10. A known systemic inflammatory condition requiring systemic treatment at screening
11. Treatment with emicizumab within 180 days before screening
12. Presence of confirmed inhibitor ≥0.6 BU at screening
13. Known history of inhibitors ≥0.6 BU in the last 5 years according to the medical records.
14. Any disorder, except for conditions associated with haemophilia, which in the investigator’s opinion might jeopardise patient’s safety or compliance with the protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. For haemophilia A patients without inhibitors: the number of treated spontaneous and traumatic bleeding episodes On demand (arm 1) From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2) From start of the new concizumab dosing regimen (week 0) up until the confirmatory analyses cut-off (at least 32 weeks)
2. For haemophilia B patients without inhibitors: the number of treated spontaneous and traumatic bleeding episodes On demand (arm 1) From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2) From start of the new concizumab dosing regimen (week 0) up until the confirmatory analyses cut-off (at least 32 weeks)

Secondary endpoints 21

1. For haemophilia A patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes Arm 4 patients who have been on stable PPX at least 24 weeks in study 4322 For previous PPX (study 4322): From the point in time where PPX is stable and up until the end of study. For concizumab PPX (trial 4307): From the point in time where the concizumab maintenance dose is confirmed, increased or decreased and up until the confirmatory analyses cut-off (at least 24 weeks).
2. For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes Arm 4 patients who have been on stable PPX at least 24 weeks in study 4322 For previous PPX (study 4322): From the point in time where PPX is stable and up until the end of study. For concizumab PPX (trial 4307): From the point in time where the concizumab maintenance dose is confirmed, increased or decreased and up until the confirmatory analyses cut-off (at least 24 weeks).
3. For haemophilia A patients without inhibitors: Number of treated spontaneous bleeding episodes On demand (arm 1) From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2) From start of the new concizumab dosing regimen (week 0) up until the confirmatory analyses cut-off (at least 32 weeks)
4. For haemophilia B patients without inhibitors: Number of treated spontaneous bleeding episodes On demand (arm 1) From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2) From start of the new concizumab dosing regimen (week 0) up until the confirmatory analyses cut-off (at least 32 weeks)
5. For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds On demand (arm 1) From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2) From start of the new concizumab dosing regimen (week 0) up until the confirmatory analyses cut-off (at least 32 weeks)
6. For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds On demand (arm 1) From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2) From start of the new concizumab dosing regimen (week 0) up until the confirmatory analyses cut-off (at least 32 weeks)
7. For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds On demand (arm 1) From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2) From start of the new concizumab dosing regimen (week 0) up until the confirmatory analyses cut-off (at least 32 weeks)
8. For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds On demand (arm 1) From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2) From start of the new concizumab dosing regimen (week 0) up until the confirmatory analyses cut-off (at least 32 weeks)
9. Number of thromboembolic events On demand (arm 1 main part) From randomisation to on demand treatment until start of concizumab treatment Concizumab (arms 2-4) Before the pause: From start of concizumab treatment up until 7 weeks after the treatment was paused and After the pause: From start of concizumab treatment up until the confirmatory analyses cut-off (at least 32 weeks) Concizumab (arm 1 extension part) From start of concizumab treatment up until the confirmatory analysis cut-off
10. Number of thromboembolic events Concizumab Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment up until the end of trial (up to 384 weeks)
11. Number of hypersensitivity type reactions On demand (arm 1 main part) From randomisation to on demand treatment up until start of concizumab treatment Concizumab (arms 2-4) Before the pause: From start of concizumab treatment up until 7 weeks after the treatment was paused and After the pause: From start of concizumab treatment up until the confirmatory analyses cut-off (at least 32 weeks) Concizumab (arm 1 extension) From start of concizumab treatment up until the confirmatory analysis cut-off
12. Number of hypersensitivity type reactions Concizumab Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment up until the end of trial (up to 384 weeks)
13. Number of injection site reactions On demand (arm 1 main part) From randomisation to on demand treatment until start of concizumab treatment Concizumab (arms 2-4) Before the pause: From start of concizumab treatment up until 7 weeks after the treatment was paused and After the pause: From start of concizumab treatment up until the confirmatory analyses cut-off (at least 32 weeks) Concizumab (arm 1 extension part) From start of concizumab treatment up until the confirmatory analysis cut-off
14. Number of injection site reactions Concizumab Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment up until the end of trial (up to 384 weeks)
15. Number of patients with antibodies to concizumab Concizumab (arms 2-4) Before the pause: From start of concizumab treatment (week 0) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment (week 0) up until the confirmatory analyses cut-off (at least 32 weeks) Concizumab (arm 1 extension part) From start of concizumab treatment (visit 9a) up until the confirmatory analysis cut-off
16. Number of patients with antibodies to concizumab Concizumab Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused as well as After the pause: From start of concizumab treatment up until the end of trial (up to 384 weeks)
17. Pre-dose (trough) concizumab plasma concentration (Ctrough) prior to the concizumab administration at week 24 (after restart)
18. Pre-dose thrombin peak prior to the concizumab administration at week 24 (after restart)
19. Pre-dose free TFPI concentration prior to the concizumab administration at week 24 (after restart)
20. Maximum concizumab plasma concentration (Cmax) from 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart)
21. Area under the concizumab plasma concentration-time curve (AUC) from 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 9

Locations

11 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 92 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications