Evaluation of Safety Following Immune Tolerance Induction Treatment With Turoctocog Alfa in Patients With Haemophilia A Following Inhibitor Development in NN7170-4213 Trial

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03588741
• Collaborator: (none)
• Enrollment: 1
• Locations: 14
• Arm: 1
• Actual Duration (Months): 12.2
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This trial is conducted in Asia, Europe and the United States of America (USA). The aim of the trial is to evaluate safety of immune tolerance induction (ITI) treatment with turoctocog alfa (a recombinant factor VIII) in patients who have developed neutralising antibodies against factor VIII after exposure to subcutaneous turoctocog alfa pegol during participation in NN7170-4213 (NCT02994407)

Condition or Disease	Intervention/Treatment	Phase
Haemophilia A	Drug: Turoctocog alfa	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Safety Following Immune Tolerance Induction Treatment With Turoctocog Alfa in Patients With Haemophilia A Following Inhibitor Development in NN7170-4213 Trial
• Actual Study Start Date: Jun 12, 2018
• Actual Primary Completion Date: Jun 19, 2019
• Actual Study Completion Date: Jun 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Turoctocog alfa	Drug: Turoctocog alfa; Intravenous (i.v., under the skin) administration.A maximum dose of 200 IU/kg daily. The maximum treatment period for this trial is 24 months and the patient(s) will be called for visit to the clinic every 3rd month.

Outcome Measures

Primary Outcome Measures

1. Number of Adverse Events [Month 0 - up to month 12]

   An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment.

Secondary Outcome Measures

1. Response to FVIII ITI Treatment (Success, Partial Success, Failure, Other) [Month 12]

   ITI treatment response was categorized as: 1. Success: Undetectable inhibitor titre <0.6 bethesda units (BU) (or lower limit of quantification [LLoQ] if above 0.6 BU); Normalised FVIII in vivo recovery, defined as ≥0.013 international units (IU) per milliliter per IU per kilogram ((IU/ml)/(IU/kg)) (66% of expected incremental recovery); turoctocog alfa half-life ≥7 hours (based on FVIII activity) after 72 hours treatment-free washout period. 2. Partial success: Inhibitor titre ≤5 BU; Clinical effect of turoctocog alfa therapy as judged by the investigator. 3. Failure (one criterion had to be fulfilled): Failure to attain defined success or partial success after 24 months of ITI treatment with turoctocog alfa; Decrease in inhibitor titre after 12 months of ITI treatment <20% compared to peak titre. 4. Other: Participants not fulfilling the above criteria e.g. early withdrawal from ITI treatment, lack of adherence to recommended ITI protocol etc.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Previous participation in the NN7170-4213 trial (male, age at least 18 years (part A) and age at least 12 years (part B))

• Development of a confirmed high titre neutralising antibody towards factor VIII (greater than 5 Bethesda Unit) after exposure to subcutaneous turoctocog alfa pegol in the NN7170-4213 trial or development of a confirmed clinically relevant low titre inhibitor (at least 0.6 to below or equal to 5 Bethesda Unit), defined as factor VIII activity measures (recovery) and/or bleedpattern indicating a lack of clinical response to factor VIII treatment

Exclusion Criteria:

• Known or suspected hypersensitivity to trial product(s) or related products, defined as allergic reactions

• Participation in another clinical trial within 1 month before screening (except participation in NN7170-4213)

• Any disorder, except for conditions associated with Haemophilia A which in the investigator's opinion might jeopardise patients' safety or compliance with the protocol

• Currently receiving immune tolerance induction treatment with a factor VIII containing product other than turoctocog alfa

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Wien		Austria	1090
2	Novo Nordisk Investigational Site	Sofia		Bulgaria	1527
3	Novo Nordisk Investigational Site	Nantes Cedex 1		France	44093
4	Novo Nordisk Investigational Site	Berlin		Germany	10249
5	Novo Nordisk Investigational Site	Duisburg		Germany	47051
6	Novo Nordisk Investigational Site	Homburg		Germany	66421
7	Novo Nordisk Investigational Site	Belgrade		Serbia	11000
8	Novo Nordisk Investigational Site	Belgrade		Serbia	11070
9	Novo Nordisk Investigational Site	Nis		Serbia	18000
10	Novo Nordisk Investigational Site	Novi Sad		Serbia	21000
11	Novo Nordisk Investigational Site	Bornova-IZMIR		Turkey	35100
12	Novo Nordisk Investigational Site	London		United Kingdom	NW3 2QG
13	Novo Nordisk Investigational Site	Oxford		United Kingdom	OX3 7LJ
14	Novo Nordisk Investigational Site	Sheffield		United Kingdom	S10 2JF

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 20, 2018

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03588741
• Other Study ID Numbers: NN7170-4345; U1111-1187-7323; 2016-003821-40
• First Posted: Jul 17, 2018
• Last Update Posted: Jul 7, 2020
• Last Verified: Jul 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
• Additional relevant MeSH terms: Hemophilia A

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 1 trial site in Germany.
Pre-assignment Detail	Previously treated participants with severe haemophilia A (FVIII activity <1% according to medical records) who had developed clinically relevant FVIII inhibitors in trial NN7170-4213 were offered immune tolerance induction (ITI) treatment with turoctocog alfa.

Arm/Group Title	Turoctocog Alfa
Arm/Group Description	The participant received intravenous (i.v.) injection of 65 international units per kilogram (IU/kg) turoctocog alfa 3 times per week. The planned treatment duration was for at least 12 months and up to a maximum period of 24 months.
Period Title: Overall Study
STARTED	1
COMPLETED	0
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Turoctocog Alfa
Arm/Group Description	The participant received intravenous (i.v.) injection of 65 international units per kilogram (IU/kg) turoctocog alfa 3 times per week. The planned treatment duration was for at least 12 months and up to a maximum period of 24 months.
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Number of Adverse Events
Description	An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment.
Time Frame	Month 0 - up to month 12

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAS) comprised of the participant(s) who initiated ITI treatment with turoctocog alfa.

Arm/Group Title	Turoctocog Alfa
Arm/Group Description	The participant received intravenous (i.v.) injection of 65 international units per kilogram (IU/kg) turoctocog alfa 3 times per week. The planned treatment duration was for at least 12 months and up to a maximum period of 24 months.
Measure Participants	1
Number [Adverse events]	6

2. Secondary Outcome

Title	Response to FVIII ITI Treatment (Success, Partial Success, Failure, Other)
Description	ITI treatment response was categorized as: 1. Success: Undetectable inhibitor titre <0.6 bethesda units (BU) (or lower limit of quantification [LLoQ] if above 0.6 BU); Normalised FVIII in vivo recovery, defined as ≥0.013 international units (IU) per milliliter per IU per kilogram ((IU/ml)/(IU/kg)) (66% of expected incremental recovery); turoctocog alfa half-life ≥7 hours (based on FVIII activity) after 72 hours treatment-free washout period. 2. Partial success: Inhibitor titre ≤5 BU; Clinical effect of turoctocog alfa therapy as judged by the investigator. 3. Failure (one criterion had to be fulfilled): Failure to attain defined success or partial success after 24 months of ITI treatment with turoctocog alfa; Decrease in inhibitor titre after 12 months of ITI treatment <20% compared to peak titre. 4. Other: Participants not fulfilling the above criteria e.g. early withdrawal from ITI treatment, lack of adherence to recommended ITI protocol etc.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

FAS comprised of the participant(s) who initiated ITI treatment with turoctocog alfa.

Arm/Group Title	Turoctocog Alfa
Arm/Group Description	The participant received intravenous (i.v.) injection of 65 international units per kilogram (IU/kg) turoctocog alfa 3 times per week. The planned treatment duration was for at least 12 months and up to a maximum period of 24 months.
Measure Participants	1
Success	0 0%
Partial success	0 0%
Failure	0 0%
Other	1 100%

Adverse Events

Time Frame	Month 0 - up to month 12
Adverse Event Reporting Description	Results are based on the safety analysis set (SAS), which comprised the participant(s) who initiated ITI treatment with turoctocog alfa.
Arm/Group Title	Turoctocog Alfa
Arm/Group Description	The participant received intravenous (i.v.) injection of 65 international units per kilogram (IU/kg) turoctocog alfa 3 times per week. The planned treatment duration was for at least 12 months and up to a maximum period of 24 months.
All Cause Mortality
	Turoctocog Alfa
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	Turoctocog Alfa
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Turoctocog Alfa
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Infections and infestations
Nasopharyngitis	1/1 (100%)	3
Musculoskeletal and connective tissue disorders
Muscle disorder	1/1 (100%)	2
Nervous system disorders
Headache	1/1 (100%)	1

Limitations/Caveats

The trial was terminated as the participant withdrew from the trial.

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.