Trial Outcomes & Findings for Efficacy and Safety of NNC 0078-0000-0007 in Patients With Congenital Haemophilia and Inhibitors (NCT NCT01392547)

NCT ID: NCT01392547

Last Updated: 2017-05-15

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 72 participants
• Primary outcome timeframe: Within 12 hours of first trial product administration
• Results posted on: 2017-05-15

Participant Flow

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.

Participant milestones

Measure	Vatreptacog Alfa and rFVIIa (All Subjects) 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.
Overall Study STARTED	72
Overall Study COMPLETED	64
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Measure	Vatreptacog Alfa and rFVIIa (All Subjects) 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.
Overall Study Adverse Event	2
Overall Study Non-compliance	2
Overall Study Withdrawal criteria	3
Overall Study Unclassified	1

Baseline Characteristics

Efficacy and Safety of NNC 0078-0000-0007 in Patients With Congenital Haemophilia and Inhibitors

Baseline characteristics by cohort

Measure	Vatrepcacog Alfa and rFVIIa n=72 Participants Subjects participating in the trial were randomised to receive vatreptacog alfa and rFVIIa in a cross-over manner.
Age, Continuous	30.19 years STANDARD_DEVIATION 13.84 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	72 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 12 hours of first trial product administration

Population: 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.

Outcome measures

Measure	Vatreptacog Alfa 80 µg/kg n=67 Participants Vatreptacog alfa was administered intravenous bolus, 1-3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed	rFVIIa 90 µg/kg n=57 Participants Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1-3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
Effective Bleeding Control Defined as no Additional Haemostatic Medication (Other Than Trial Product) Given Additional haemostatic given	22 bleeding episodes	16 bleeding episodes
Effective Bleeding Control Defined as no Additional Haemostatic Medication (Other Than Trial Product) Given Additional haemostatic not given	318 bleeding episodes	211 bleeding episodes

SECONDARY outcome

Timeframe: Up to 48 hours after first trial product administration

Population: 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.

Outcome measures

Measure	Vatreptacog Alfa 80 µg/kg n=67 Participants Vatreptacog alfa was administered intravenous bolus, 1-3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed	rFVIIa 90 µg/kg n=57 Participants Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1-3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
Effective and Sustained Bleeding Control Additional haemostatic given	53 bleeding episodes	51 bleeding episodes
Effective and Sustained Bleeding Control Additional haemostatic not given	268 bleeding episodes	163 bleeding episodes

SECONDARY outcome

Timeframe: Up to 6 hours after first trial product administration

Population: 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.

Outcome measures

Measure	Vatreptacog Alfa 80 µg/kg n=67 Participants Vatreptacog alfa was administered intravenous bolus, 1-3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed	rFVIIa 90 µg/kg n=57 Participants Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1-3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
Number of Doses of Trial Product Given for Each Acute Bleed 1 dose	51 bleeding episodes	23 bleeding episodes
Number of Doses of Trial Product Given for Each Acute Bleed 2 doses	94 bleeding episodes	62 bleeding episodes
Number of Doses of Trial Product Given for Each Acute Bleed 3 doses	195 bleeding episodes	142 bleeding episodes

SECONDARY outcome

Timeframe: Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product.

Population: 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.

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.

Outcome measures

Measure	Vatreptacog Alfa 80 µg/kg n=72 Participants Vatreptacog alfa was administered intravenous bolus, 1-3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed	rFVIIa 90 µg/kg n=57 Participants Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1-3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
Number of Adverse Events All adverse events	55 events	11 events
Number of Adverse Events Mild adverse events	33 events	5 events
Number of Adverse Events Moderate adverse events	15 events	2 events
Number of Adverse Events Severe adverse events	7 events	4 events

SECONDARY outcome

Timeframe: 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.

Population: 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.

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

Outcome measures

Measure	Vatreptacog Alfa 80 µg/kg n=72 Participants Vatreptacog alfa was administered intravenous bolus, 1-3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed	rFVIIa 90 µg/kg n=57 Participants Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1-3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
Immunogenicity (Inhibitor Development) Positive for anti-vatreptacog alfa	8 Subjects	0 Subjects
Immunogenicity (Inhibitor Development) Cross-reactive with rFVIIa	4 Subjects	0 Subjects
Immunogenicity (Inhibitor Development) Positive for anti-rFVIIa	0 Subjects	1 Subjects
Immunogenicity (Inhibitor Development) In vitro vatreptacog alfa-neutralising	1 Subjects	0 Subjects
Immunogenicity (Inhibitor Development) In vitro FVII/rFVIIa-neutralising	0 Subjects	0 Subjects

Adverse Events

Vatreptacog Alfa 80 µg/kg

Serious events: 4 serious events

Other events: 5 other events

Deaths: 0 deaths

rFVIIa 90 µg/kg

Serious events: 4 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vatreptacog Alfa 80 µg/kg n=72 participants at risk Vatreptacog alfa was administered intravenous bolus, 1-3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed	rFVIIa 90 µg/kg n=57 participants at risk Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1-3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
Gastrointestinal disorders Dental caries	1.4% 1/72 • Number of events 1 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.	0.00% 0/57 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.
Gastrointestinal disorders Retroperitoneal haemorrhage	0.00% 0/72 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.	1.8% 1/57 • Number of events 1 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/72 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.	1.8% 1/57 • Number of events 1 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.
Infections and infestations Pyelonephritis	0.00% 0/72 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.	1.8% 1/57 • Number of events 1 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.
Infections and infestations Rectal abscess	0.00% 0/72 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.	1.8% 1/57 • Number of events 1 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	0.00% 0/72 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.	1.8% 1/57 • Number of events 1 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.
Injury, poisoning and procedural complications Lower limb fracture	1.4% 1/72 • Number of events 1 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.	0.00% 0/57 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.
Skin and subcutaneous tissue disorders Telangiectasia	1.4% 1/72 • Number of events 1 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.	0.00% 0/57 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.
Vascular disorders Haematoma	1.4% 1/72 • Number of events 1 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.	0.00% 0/57 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.

Other adverse events

Measure	Vatreptacog Alfa 80 µg/kg n=72 participants at risk Vatreptacog alfa was administered intravenous bolus, 1-3 doses at 80 µg/kg body weight until haemostasis was achieved for a bleed	rFVIIa 90 µg/kg n=57 participants at risk Recombinant factor VIIa (rFVIIa) was administered intravenous bolus, 1-3 doses 90 µg/kg body weight until haemostasis was achieved for a bleed
Investigations Drug specific antibody present	6.9% 5/72 • Number of events 8 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.	5.3% 3/57 • Number of events 4 • Adverse events were captured from the time of consent to 1 month (+14 days) after last administration of trial product. All patients exposed to at least one dose of trial product was included in the safety analysis set.

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Email: clinicaltrials@novonordisk.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER