guardian 10: Research Study to Look at Side Effects During Regular Injection With Factor VIII Medicine Named Turoctocog Alfa for a 8 Weeks Period

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03449342
• Collaborator: (none)
• Enrollment: 60
• Locations: 10
• Arm: 1
• Actual Duration (Months): 13.7
• Patients Per Site: 6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will test the well-known medicine turoctocog alfa for any side effects. The purpose is to test turoctocog alfa for any side effects in the Indian population. The participants will get turoctocog alfa. Turoctocog alfa is already a well-known medicine in India, and can be prescribed by the study doctor. The participants will get an injection every second day or 3 times per week. This is decided by the study doctor. The study doctor will decide the amount and how often the participants must take the medicine. The study will last for about 16 weeks. The participants will have 5 visits with the study doctor. If the participants agree to participate in this study, the participants will receive the first injection at the second visit, thereafter the participants will be trained to do the injection by themself.

Condition or Disease	Intervention/Treatment	Phase
Congenital Bleeding Disorder; Haemophilia A	Drug: turoctocog alfa	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety of Turoctocog Alfa for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Patients With Moderate or Severe Haemophilia A in India
• Actual Study Start Date: Mar 1, 2018
• Actual Primary Completion Date: Mar 25, 2019
• Actual Study Completion Date: Apr 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Turoctocog alfa Previously treated moderate or severe haemophilia A patients will receive routine prophylaxis treatment and treatment of bleeding episodes.	Drug: turoctocog alfa; Patients will receive standard prophylaxis treatment and treatment of bleeding episodes, according to label. Trial product will be administered as intravenous injections (i.v.)

Outcome Measures

Primary Outcome Measures

1. Occurrence of Confirmed FVIII Inhibitor Development (≥ 0.6 BU) [Weeks 0-8]

   The number of participants who confirmed the presence of FVIII inhibitor development (≥ 0.6 BU) during 8 weeks of treatment period.

Secondary Outcome Measures

1. Incidence of Adverse Drug Reactions (ARs) and Serious Adverse Reactions (SARs) [Weeks 0-12]

   Incidence of adverse drug reactions (ARs) and serious adverse reactions (SARs) were calculated as the number of adverse reactions per patient years. All presented ARs and SARs are treatment emergent and related to trial product, which were defined as the events reported after trial product administration until the follow-up, 12 weeks after first treatment.

2. Number of Bleeding Episodes With Successful Haemostatic Effect of Turoctocog Alfa [Weeks 0-8]

   The haemostatic effect (HE) of turoctocog alfa when used for treatment of bleeding episodes was evaluated during 8 weeks of treatment. Successful haemostatic effect means the haemostatic response when used for treatment of a bleeding episode was either excellent or good. Excellent haemostatic respose: Abrupt pain relief and/or clear improvement in objective signs of bleeding episode within approximately 8 hours after a single injection. Good haemostatic response: Definite pain relief and/or improvement in signs of bleeding episode within approximately 8 hours after an injection, but possibly requiring more than 1 injection for complete resolution.

3. Total Annualised Consumption of Turoctocog Alfa [Weeks 0-8]

   Total consumption of turoctocog alfa was evaluated during 8 weeks of treatment and it was presented as IU of turoctocog alfa/kg body weight (BW) per year per participant.

4. Incidence of Allergic or Infusion Reactions Related to the Trial Product [Weeks 0-12]

   Incidence of allergic or infusion reactions related to trial products were calculated as the number of reactions per patient years. Allergic reactions are a class of adverse events related to allergy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria: - 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 - Male, age above or equal to 12 years at the time of signing informed consent - Patients with the diagnosis of congenital moderate or severe Haemophilia A based on medical records. (FVIII below or equal to 5%) - Documented history of at least 150 EDs (exposure days) to FVIII containing products Exclusion Criteria: - Confirmed inhibitors to FVIII (above or equal to 0.6 BU) at screening as assessed by central laboratory - History of FVIII inhibitors - Known or suspected hypersensitivity to trial product(s) or related products - Previous participation in this trial. Participation is defined as signed informed consent - Participation in any clinical trial of an approved or non-approved investigational medicinal product within 1 month before screening (visit 1) - Any disorder, except for conditions associated with haemophilia A, which in the investigator's opinion might jeopardise patient's safety or compliance with the protocol - Immunocompromised patients due to HIV infection (defined as viral load above or equal to 400.000 copies/mL and/or CD4+ lymphocyte count below or equal to 200/μL). HIV status and CD4+ lymphocyte count /viral load results may be obtained at screening or from available medical records; results must be not older than 6 months - Known congenital or acquired coagulation disorders other than haemophilia A - Mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560034
2	Novo Nordisk Investigational Site	Cochin	Kerala	India	682041
3	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400012
4	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411004
5	Novo Nordisk Investigational Site	New Dehli	New Delhi	India	110029
6	Novo Nordisk Investigational Site	Ludhiana	Punjab	India	141008
7	Novo Nordisk Investigational Site	Vellore	Tamil Nadu	India	632004
8	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	70014
9	Novo Nordisk Investigational Site	Kolkatta	West Bengal	India	70014
10	Novo Nordisk Investigational Site	New Delhi		India	110029

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 26, 2019

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03449342
• Other Study ID Numbers: NN7008-4304; 2017-002281-46; U1111-1179-5950
• First Posted: Feb 28, 2018
• Last Update Posted: Apr 17, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Hemostatic Disorders; Hemophilia A; Blood Coagulation Disorders; Hemorrhage

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 10 sites in India.

Arm/Group Title	Adolescents (12 - <18 Years)	Adults (≥18 Years)
Arm/Group Description	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.
Period Title: Overall Study
STARTED	10	50
COMPLETED	10	50
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Adolescents (12 - <18 Years)	Adults (≥18 Years)	Total
Arm/Group Description	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.	Total of all reporting groups
Overall Participants	10	50	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.90 (1.91)	27.10 (7.28)	24.90 (8.32)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	10 100%	50 100%	60 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	10 100%	50 100%	60 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	10 100%	50 100%	60 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Occurrence of Confirmed FVIII Inhibitor Development (≥ 0.6 BU)
Description	The number of participants who confirmed the presence of FVIII inhibitor development (≥ 0.6 BU) during 8 weeks of treatment period.
Time Frame	Weeks 0-8

Outcome Measure Data

Analysis Population Description

Results are based on the full analysis set (FAS), that included all dosed participants with data after dosing during 8 weeks of treatment.

Arm/Group Title	Adolescents (12 - <18 Years)	Adults (≥18 Years)
Arm/Group Description	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.
Measure Participants	10	50
Count of Participants [Participants]	0 0%	0 0%

2. Secondary Outcome

Title	Incidence of Adverse Drug Reactions (ARs) and Serious Adverse Reactions (SARs)
Description	Incidence of adverse drug reactions (ARs) and serious adverse reactions (SARs) were calculated as the number of adverse reactions per patient years. All presented ARs and SARs are treatment emergent and related to trial product, which were defined as the events reported after trial product administration until the follow-up, 12 weeks after first treatment.
Time Frame	Weeks 0-12

Outcome Measure Data

Analysis Population Description

Results are based on the safety analysis set (SAS), that included all dosed participants with data after dosing during 8 weeks of treatment.

Arm/Group Title	Adolescents (12 - <18 Years)	Adults (≥18 Years)
Arm/Group Description	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.
Measure Participants	10	50
Adverse drug reaction	0	0
Serious adverse reactions	0	0

3. Secondary Outcome

Title	Number of Bleeding Episodes With Successful Haemostatic Effect of Turoctocog Alfa
Description	The haemostatic effect (HE) of turoctocog alfa when used for treatment of bleeding episodes was evaluated during 8 weeks of treatment. Successful haemostatic effect means the haemostatic response when used for treatment of a bleeding episode was either excellent or good. Excellent haemostatic respose: Abrupt pain relief and/or clear improvement in objective signs of bleeding episode within approximately 8 hours after a single injection. Good haemostatic response: Definite pain relief and/or improvement in signs of bleeding episode within approximately 8 hours after an injection, but possibly requiring more than 1 injection for complete resolution.
Time Frame	Weeks 0-8

Outcome Measure Data

Analysis Population Description

Results are based on the FAS that included all dosed participants with data after dosing during 8 weeks of treatment. "Overall Number of Participants Analyzed" = Number of participants with bleeding episodes treated with turoctocog alfa.

Arm/Group Title	Adolescents (12 - <18 Years)	Adults (≥18 Years)
Arm/Group Description	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.
Measure Participants	2	17
Measure bleeding episodes	3	46
Number [Bleeding episodes with successfull HE]	2	38

4. Secondary Outcome

Title	Total Annualised Consumption of Turoctocog Alfa
Description	Total consumption of turoctocog alfa was evaluated during 8 weeks of treatment and it was presented as IU of turoctocog alfa/kg body weight (BW) per year per participant.
Time Frame	Weeks 0-8

Outcome Measure Data

Analysis Population Description

Results are based on the FAS that included all dosed participants with data after dosing during 8 weeks of treatment.

Arm/Group Title	Adolescents (12 - <18 Years)	Adults (≥18 Years)
Arm/Group Description	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.
Measure Participants	10	50
Mean (Standard Deviation) [IU/kg BW/year/participant]	7030 (1053)	6086 (1735)

5. Secondary Outcome

Title	Incidence of Allergic or Infusion Reactions Related to the Trial Product
Description	Incidence of allergic or infusion reactions related to trial products were calculated as the number of reactions per patient years. Allergic reactions are a class of adverse events related to allergy.
Time Frame	Weeks 0-12

Outcome Measure Data

Analysis Population Description

Results are based on the SAS, that included all dosed participants with data after dosing during 8 weeks of treatment.

Arm/Group Title	Adolescents (12 - <18 Years)	Adults (≥18 Years)
Arm/Group Description	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.
Measure Participants	10	50
Number [Number of reactions per patient years]	0	0

Adverse Events

Time Frame	Week 0 - 12 (8 weeks of treatment period + 4 weeks of follow-up period).
Adverse Event Reporting Description	All the adverse events are based on the safety analysis set (SAS) which included all dosed participants with data after dosing.
Arm/Group Title	Adolescents (12 - <18 Years)		Adults (>=18 Years)
Arm/Group Description	Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.		Participants were to receive prophylactic (preventive) treatment of turoctocog alfa as intravenous (i.v.) injections at a frequency of 'every second day' or '3 times a week' at a dose in the range of 20-50 IU/kg at the investigator's discretion. Dosing for prophylaxis was according to the approved prescribing information. The total treatment duration for each participant was 8 weeks. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations.
All Cause Mortality
	Adolescents (12 - <18 Years)		Adults (>=18 Years)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/50 (0%)
Serious Adverse Events
	Adolescents (12 - <18 Years)		Adults (>=18 Years)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Adolescents (12 - <18 Years)		Adults (>=18 Years)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		2/50 (4%)
Infections and infestations
Upper respiratory tract infection	1/10 (10%)	2	2/50 (4%)	2
Nervous system disorders
Headache	1/10 (10%)	1	0/50 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.