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

• ClinicalTrials.gov Identifier: NCT03588741
• Recruitment Status: Terminated
• First Posted: July 17, 2018
• Results First Posted: July 7, 2020
• Last Update Posted: July 7, 2020
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Haemophilia A
• Intervention: Drug: Turoctocog alfa
• Enrollment: 1

Participant Flow

Recruitment Details	The trial was conducted at 1 trial site in Germany.
Pre-assignment Details	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
Reason Not Completed
Withdrawal by Subject	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 Number of Baseline Participants		1
Baseline Analysis Population Description		Full analysis set (FAS) comprised of the participant(s) who initiated ITI treatment with turoctocog alfa.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	1 100.0%
	>=65 years	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	Female	0 0.0%
	Male	1 100.0%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.

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.
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: 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.
Overall Number of Participants Analyzed	1
Measure Type: Count of Participants; Unit of Measure: Participants
Success	0 0.0%
Partial success	0 0.0%
Failure	0 0.0%
Other	1 100.0%

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 (%)
Total	0/1 (0.00%)
Serious Adverse Events
	Turoctocog Alfa
	Affected / at Risk (%)	# Events
Total	0/1 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Turoctocog Alfa
	Affected / at Risk (%)	# Events
Total	1/1 (100.00%)
Infections and infestations
Nasopharyngitis † 1	1/1 (100.00%)	3
Musculoskeletal and connective tissue disorders
Muscle disorder † 1	1/1 (100.00%)	2
Nervous system disorders
Headache † 1	1/1 (100.00%)	1
1 Term from vocabulary, 22.0; † Indicates events were collected by systematic assessment

Limitations and 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.

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.

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.

Results Point of Contact

• Name/Title: Clinical Reporting Anchor and Disclosure (1452)
• Organization: Novo Nordisk A/S
• Phone: (+1) 866-867-7178
• EMail: clinicaltrials@novonordisk.com

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03588741
• Other Study ID Numbers: NN7170-4345; U1111-1187-7323 ( Other Identifier: WHO ); 2016-003821-40 ( EudraCT Number )
• First Submitted: June 12, 2018
• First Posted: July 17, 2018
• Results First Submitted: June 12, 2020
• Results First Posted: July 7, 2020
• Last Update Posted: July 7, 2020