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Efficacy and Safety of NNC 0078-0000-0007 in Patients With Congenital Haemophilia and Inhibitors (adept™2)

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ClinicalTrials.gov Identifier: NCT01392547
Recruitment Status : Completed
First Posted : July 12, 2011
Results First Posted : December 6, 2013
Last Update Posted : May 15, 2017
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Congenital Bleeding Disorder
Haemophilia A With Inhibitors
Haemophilia B With Inhibitors
Interventions Drug: vatreptacog alfa (activated)
Drug: eptacog alfa (activated)
Enrollment 72
Recruitment Details Patients treated with vatreptacog alfa were recruited from a total of 46 sites globally in 18 countries, including Austria, Brazil, Croatia, Greece, Hungary, Italy, Japan, Malaysia, Poland, Romania, Russia, Serbia, South Africa, Taiwan, Thailand, Turkey, United Kingdom and United States of America.
Pre-assignment Details  
Arm/Group Title Vatreptacog Alfa and rFVIIa (All Subjects)
Hide Arm/Group Description Subjects participating in the trial were randomised to receive vatreptacog alfa and rFVIIa in a cross-over manner. Subjects participating in the trial had bleeding episodes randomised to treatment with either vatraptacog alfa or rFVIIa in an independent manner for each bleeding episodes. Of the 72 subjects, 3 subjects did not have any bleeds.
Period Title: Overall Study
Started 72 [1]
Completed 64
Not Completed 8
Reason Not Completed
Adverse Event             2
Non-compliance             2
Withdrawal criteria             3
Unclassified             1
[1]
567 bleeds by 69 subjects, 340 were treated with vatreptacog alfa and 227 with rFVIIa
Arm/Group Title Vatrepcacog Alfa and rFVIIa
Hide Arm/Group Description Subjects participating in the trial were randomised to receive vatreptacog alfa and rFVIIa in a cross-over manner.
Overall Number of Baseline Participants 72
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 72 participants
30.19  (13.84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants
Female
0
   0.0%
Male
72
 100.0%
1.Primary Outcome
Title Effective Bleeding Control Defined as no Additional Haemostatic Medication (Other Than Trial Product) Given
Hide Description [Not Specified]
Time Frame Within 12 hours of first trial product administration
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with ≥1 efficacy data point. 567 bleeds in 69 patients were treated with vatreptacog/rFVIIa in random sequence. Bleeds excluded in case of identical consecutive treatments, use of both trial products, unknown dispensing unit number.
Arm/Group Title Vatreptacog Alfa 80 µg/kg rFVIIa 90 µg/kg
Hide Arm/Group Description:
Vatreptacog alfa was administered intravenous bolus, 1−3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed
Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1−3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
Overall Number of Participants Analyzed 67 57
Measure Type: Number
Unit of Measure: bleeding episodes
Additional haemostatic given 22 16
Additional haemostatic not given 318 211
2.Secondary Outcome
Title Effective and Sustained Bleeding Control
Hide Description [Not Specified]
Time Frame Up to 48 hours after first trial product administration
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with ≥1 efficacy data point. 567 bleeds in 69 patients were treated with vatreptacog/rFVIIa in random sequence. Bleeds excluded in case of identical consecutive treatments, use of both trial products, unknown dispensing unit number.
Arm/Group Title Vatreptacog Alfa 80 µg/kg rFVIIa 90 µg/kg
Hide Arm/Group Description:
Vatreptacog alfa was administered intravenous bolus, 1−3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed
Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1−3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
Overall Number of Participants Analyzed 67 57
Measure Type: Number
Unit of Measure: bleeding episodes
Additional haemostatic given 53 51
Additional haemostatic not given 268 163
3.Secondary Outcome
Title Number of Doses of Trial Product Given for Each Acute Bleed
Hide Description [Not Specified]
Time Frame Up to 6 hours after first trial product administration
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with ≥1 efficacy data point. 567 bleeds in 69 patients were treated with vatreptacog/rFVIIa in random sequence. Bleeds excluded in case of identical consecutive treatments, use of both trial products, unknown dispensing unit number.
Arm/Group Title Vatreptacog Alfa 80 µg/kg rFVIIa 90 µg/kg
Hide Arm/Group Description:
Vatreptacog alfa was administered intravenous bolus, 1−3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed
Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1−3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
Overall Number of Participants Analyzed 67 57
Measure Type: Number
Unit of Measure: bleeding episodes
1 dose 51 23
2 doses 94 62
3 doses 195 142
4.Secondary Outcome
Title Number of Adverse Events
Hide Description Any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time Frame Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients exposed to at least one dose of trial product was included in the safety analysis set. Patients received scheduled doses with rFVIIa, and treatment (rVIIa and vatreptacog alfa) for each bleeding episode.
Arm/Group Title Vatreptacog Alfa 80 µg/kg rFVIIa 90 µg/kg
Hide Arm/Group Description:
Vatreptacog alfa was administered intravenous bolus, 1−3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed
Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1−3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
Overall Number of Participants Analyzed 72 57
Measure Type: Number
Unit of Measure: events
All adverse events 55 11
Mild adverse events 33 5
Moderate adverse events 15 2
Severe adverse events 7 4
5.Secondary Outcome
Title Immunogenicity (Inhibitor Development)
Hide Description Immunogenicity was tested by formation of neutralising antibodies towards vatreptacog alfa and/or FVII. Radioimmunoassay using [125I]-labelled vatreptacog alfa or rFVIIa was used to screen plasma samples for development of anti-drug antibodies
Time Frame Adverse events were captured from the time of consent to the end of trial visit 1 month (+14 days) after last administration of trial product.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients exposed to at least one dose of trial product was included in the safety analysis set. Patients received scheduled doses with rFVIIa, and treatment (rVIIa and vatreptacog alfa) for each bleeding episode.
Arm/Group Title Vatreptacog Alfa 80 µg/kg rFVIIa 90 µg/kg
Hide Arm/Group Description:
Vatreptacog alfa was administered intravenous bolus, 1−3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed
Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1−3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
Overall Number of Participants Analyzed 72 57
Measure Type: Number
Unit of Measure: Subjects
Positive for anti-vatreptacog alfa 8 0
Cross-reactive with rFVIIa 4 0
Positive for anti-rFVIIa 0 1
In vitro vatreptacog alfa-neutralising 1 0
In vitro FVII/rFVIIa-neutralising 0 0
Time Frame Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product.
Adverse Event Reporting Description All patients exposed to at least one dose of trial product was included in the safety analysis set.
 
Arm/Group Title Vatreptacog Alfa 80 µg/kg rFVIIa 90 µg/kg
Hide Arm/Group Description Vatreptacog alfa was administered intravenous bolus, 1−3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1−3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
All-Cause Mortality
Vatreptacog Alfa 80 µg/kg rFVIIa 90 µg/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Vatreptacog Alfa 80 µg/kg rFVIIa 90 µg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/72 (5.56%)      4/57 (7.02%)    
Gastrointestinal disorders     
Dental caries  1  1/72 (1.39%)  1 0/57 (0.00%)  0
Retroperitoneal haemorrhage  1  0/72 (0.00%)  0 1/57 (1.75%)  1
Small intestinal obstruction  1  0/72 (0.00%)  0 1/57 (1.75%)  1
Infections and infestations     
Pyelonephritis  1  0/72 (0.00%)  0 1/57 (1.75%)  1
Rectal abscess  1  0/72 (0.00%)  0 1/57 (1.75%)  1
Injury, poisoning and procedural complications     
Arteriovenous fistula thrombosis  1  0/72 (0.00%)  0 1/57 (1.75%)  1
Lower limb fracture  1  1/72 (1.39%)  1 0/57 (0.00%)  0
Skin and subcutaneous tissue disorders     
Telangiectasia  1  1/72 (1.39%)  1 0/57 (0.00%)  0
Vascular disorders     
Haematoma  1  1/72 (1.39%)  1 0/57 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vatreptacog Alfa 80 µg/kg rFVIIa 90 µg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/72 (6.94%)      3/57 (5.26%)    
Investigations     
Drug specific antibody present  1  5/72 (6.94%)  8 3/57 (5.26%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Novo Nordisk maintains the right to be informed of any Investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Novo Nordisk reserves the right to prior review of such publications and to ask for delay of publication of individual site results until after the primary manuscript is accepted for publication.
Results Point of Contact
Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01392547     History of Changes
Other Study ID Numbers: NN1731-3562
2010-023803-92 ( EudraCT Number )
U1111-1118-2228 ( Other Identifier: WHO )
JapicCTI-111595 ( Registry Identifier: JAPIC )
First Submitted: July 8, 2011
First Posted: July 12, 2011
Results First Submitted: September 27, 2013
Results First Posted: December 6, 2013
Last Update Posted: May 15, 2017