Trial Outcomes & Findings for Clinical Study to Investigate the Efficacy and Safety of Wilate During Prophylaxis in Previously Treated Patients With VWD (NCT NCT04052698)

NCT ID: NCT04052698

Last Updated: 2023-10-25

Results Overview

Estimated TABR number calculated using a negative binomial counting regression model. Comparison between this number calculated for studies WIL-29 (NCT04053699) and WIL-31. For the comparison of results from WIL-31 to WIL-29 an estimated total annualized bleeding rate was calculated for each cohort, and compared with a negative binomial counting model. As these were estimated rates, there is only one value for each cohort with no measure of spread

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 43 participants
• Primary outcome timeframe: 12 Months
• Results posted on: 2023-10-25

Participant Flow

Overall, 43 patients were enrolled and treated at 14 study sites worldwide. Twenty-two patients had Type 3 VWD, 10 patients were aged 6-11 years, and 8 patients were aged 12-16 years. Thirty-three patients were evaluable for the primary endpoint. The sample sizes were therefore met.

Participant milestones

Measure	Wilate Routine Prophylaxis in Patients With VWD Prophylactic treatment with Wilate of previously treated patients (PTPs) with Type 3, Type 2 (except 2N), or severe Type 1 VWD.
Overall Study STARTED	43
Overall Study Safety Analysis Set (SAF)	43
Overall Study Modified Full Analysis Set (mFAS)	33
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Study to Investigate the Efficacy and Safety of Wilate During Prophylaxis in Previously Treated Patients With VWD

Baseline characteristics by cohort

Measure	Wilate Routine Prophylaxis in Patients With VWD n=43 Participants Prophylactic treatment with Wilate of previously treated patients (PTPs) with Type 3, Type 2 (except 2N), or severe Type 1 VWD.
Age, Continuous	22.4 years STANDARD_DEVIATION 14.59 • n=5 Participants
Sex: Female, Male Sex · Female	17 Participants n=5 Participants
Sex: Female, Male Sex · Male	26 Participants n=5 Participants
Race/Ethnicity, Customized White	42 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Height	161.3 centimetres STANDARD_DEVIATION 18.22 • n=5 Participants
Weight	62.4 kilograms STANDARD_DEVIATION 24.96 • n=5 Participants
Body Mass Index (BMI)	22.9 kg/m2 STANDARD_DEVIATION 6.21 • n=5 Participants
Blood Group Blood Group A	22 Participants n=5 Participants
Blood Group Blood Group B	6 Participants n=5 Participants
Blood Group Blood Group AB	1 Participants n=5 Participants
Blood Group Blood Group O	14 Participants n=5 Participants
VWD Type Severe Type 1 VWD	6 Participants n=5 Participants
VWD Type Type 2 VWD	5 Participants n=5 Participants
VWD Type Type 3 VWD	22 Participants n=5 Participants
VWD Type Unconfirmed disease status	10 Participants n=5 Participants
No Von Willebrand Factor inhibitor history	43 Participants n=5 Participants
No Factor VIII Inhibitor History	43 Participants n=5 Participants
Family History of VWD Yes	22 Participants n=5 Participants
Family History of VWD No	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

The TABR was calculated as the total number of spontaneous bleeds, traumatic bleeds, and other bleeds (except menstrual bleeds) occurring in the time period between first dose of the investigational medicinal product (IMP) and the Study Completion Visit, divided by the duration (in years) between first dose of IMP and the Study Completion Visit.

Outcome measures

Measure	6-<12 Yrs n=9 Participants Age of patients	12-<17 Yrs n=6 Participants Age of patients	≥17 Yrs n=18 Participants Age of patients	Total n=33 Participants Total annualized bleeding rates in study WIL-31
Total Annualized Bleeding Rate (TABR)	3.73 bleeding events per year Standard Deviation 4.838	4.28 bleeding events per year Standard Deviation 4.647	6.31 bleeding events per year Standard Deviation 9.634	5.24 bleeding events per year Standard Deviation 7.745

PRIMARY outcome

Timeframe: 12 Months

Estimated TABR number calculated using a negative binomial counting regression model. Comparison between this number calculated for studies WIL-29 (NCT04053699) and WIL-31. For the comparison of results from WIL-31 to WIL-29 an estimated total annualized bleeding rate was calculated for each cohort, and compared with a negative binomial counting model. As these were estimated rates, there is only one value for each cohort with no measure of spread

Outcome measures

Measure	6-<12 Yrs n=33 Participants Age of patients	12-<17 Yrs n=33 Participants Age of patients	≥17 Yrs Age of patients	Total Total annualized bleeding rates in study WIL-31
Comparison of Total Annualized Bleeding Rates (TABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29	33.3751 bleeding events per year	5.4914 bleeding events per year	—	—

SECONDARY outcome

Timeframe: 12 months

Spontaneous annualized bleeding rate (SABR) calculated in analogy with TABR

Outcome measures

Measure	6-<12 Yrs n=9 Participants Age of patients	12-<17 Yrs n=6 Participants Age of patients	≥17 Yrs n=18 Participants Age of patients	Total n=33 Participants Total annualized bleeding rates in study WIL-31
Spontaneous Annualized Bleeding Rate (SABR)	2.53 bleeding events per year Standard Deviation 4.145	6 bleeding events per year Standard Deviation 1.49	4.16 bleeding events per year Standard Deviation 7.382	3.23 bleeding events per year Standard Deviation 5.915

SECONDARY outcome

Timeframe: 12 Months

Estimated SABR number calculated using a negative binomial counting regression model. Comparison between this number calculated for studies WIL-29 (NCT04053699) and WIL-31. For the comparison of results from WIL-31 to WIL-29 an estimated total annualized bleeding rate was calculated for each cohort, and compared with a negative binomial counting model. As these were estimated rates, there is only one value for each cohort with no measure of spread

Outcome measures

Measure	6-<12 Yrs n=33 Participants Age of patients	12-<17 Yrs n=33 Participants Age of patients	≥17 Yrs Age of patients	Total Total annualized bleeding rates in study WIL-31
Comparison of Spontaneous Annualized Bleeding Rates (SABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29.	24.4168 bleeding events per year	3.3925 bleeding events per year	—	—

SECONDARY outcome

Timeframe: 12 months

Data on the consumption of Wilate (VWF/FVIII IU/kg per month and per week per patient) for prophylactic treatment

Outcome measures

Measure	6-<12 Yrs n=33 Participants Age of patients	12-<17 Yrs Age of patients	≥17 Yrs Age of patients	Total Total annualized bleeding rates in study WIL-31
Wilate Consumption for Prophylaxis (mFAS Population) Dose per exposure day	31.06 IU/kilogram Standard Deviation 6.589	—	—	—
Wilate Consumption for Prophylaxis (mFAS Population) Dose per injection	31.04 IU/kilogram Standard Deviation 6.559	—	—	—
Wilate Consumption for Prophylaxis (mFAS Population) Dose per Week in Study	66.06 IU/kilogram Standard Deviation 23.359	—	—	—
Wilate Consumption for Prophylaxis (mFAS Population) Dose per Month in Study	287.26 IU/kilogram Standard Deviation 101.569	—	—	—

SECONDARY outcome

Timeframe: From baseline and 12-month visit

Incremental VWF:RCo IVR of Wilate over time (at baseline and at 1, 2, 3, 6, 9, and 12 months of treatment)

Outcome measures

Measure	6-<12 Yrs n=33 Participants Age of patients	12-<17 Yrs Age of patients	≥17 Yrs Age of patients	Total Total annualized bleeding rates in study WIL-31
Incremental In Vivo Recovery (IVR) of Von Willebrand Factor Activity (VWF:RCo) Baseline	1.439 kg/dL Standard Deviation 0.5259	—	—	—
Incremental In Vivo Recovery (IVR) of Von Willebrand Factor Activity (VWF:RCo) 12-Month Visit	1.273 kg/dL Standard Deviation 0.6040	—	—	—

SECONDARY outcome

Timeframe: Baseline and 12-month visit

FVIII:C of Wilate in pediatric patients (at baseline PK visit) measured by chromogenic assay

Outcome measures

Measure	6-<12 Yrs n=33 Participants Age of patients	12-<17 Yrs Age of patients	≥17 Yrs Age of patients	Total Total annualized bleeding rates in study WIL-31
Incremental In Vivo Recovery (IVR) of FVIII Baseline	1.697 kg/dL Interval 1.47 to 1.95	—	—	—
Incremental In Vivo Recovery (IVR) of FVIII 12-month visit	2.140 kg/dL Interval 2.04 to 2.48	—	—	—

SECONDARY outcome

Timeframe: 12 months

Treatment efficacy will be assessed at the end of a BE by the patient using predefined criteria of 'Excellent', 'Good', 'Moderate' or 'None'. All effectiveness ratings assessed as either "excellent" or "good" will be considered "successfully treated".

Outcome measures

Measure	6-<12 Yrs n=121 Bleeding events treated Age of patients	12-<17 Yrs Age of patients	≥17 Yrs Age of patients	Total Total annualized bleeding rates in study WIL-31
Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs) Excellent	109 bleeding episodes treated	—	—	—
Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs) Good	11 bleeding episodes treated	—	—	—
Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs) Moderate	1 bleeding episodes treated	—	—	—
Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs) None	0 bleeding episodes treated	—	—	—

SECONDARY outcome

Timeframe: 12 months

Data on the exposure days of Wilate prophylactic treatment

Outcome measures

Measure	6-<12 Yrs n=33 Participants Age of patients	12-<17 Yrs Age of patients	≥17 Yrs Age of patients	Total Total annualized bleeding rates in study WIL-31
Wilate Exposure for Prophylaxis (mFAS Population)	105.55 days Standard Deviation 32.782	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: A total of 3 patients had 13 surgeries that were included in the SURG population.10 of these surgeries were minor and 3 were major.

Efficacy will be assessed by the surgeon at the end of surgery and by the hematologist at the end of the postoperative period using predefined criteria of 'Excellent', 'Good', 'Moderate' or 'None'. In addition, an overall assessment using the 'Excellent', 'Good', 'Moderate' or 'None' scale taking both the intra- and postoperative assessments into account will be made at the end of the postoperative period by the investigator based on an algorithm.

Outcome measures

Measure	6-<12 Yrs n=13 Number of surgeries Age of patients	12-<17 Yrs Age of patients	≥17 Yrs Age of patients	Total Total annualized bleeding rates in study WIL-31
Efficacy Rating for Wilate in Surgical Prophylaxis Efficacy Assessment Rated 'Excellent'	13 surgeries	—	—	—
Efficacy Rating for Wilate in Surgical Prophylaxis Efficacy Assessment Rated 'Good'	0 surgeries	—	—	—
Efficacy Rating for Wilate in Surgical Prophylaxis Efficacy Assessment Rated 'Moderate'	0 surgeries	—	—	—
Efficacy Rating for Wilate in Surgical Prophylaxis Efficacy Assessment Rated 'None'	0 surgeries	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: Analysis provided on a total number of 31 completed PROMIS-29 questionnaires.

QoL assessment based on the results from the PROMIS-29 (Patient-Reported Outcomes Measurement Information System) survey, which monitors and evaluates the physical, mental, and social health in all patients. The survey covers seven domains from the most relevant areas of self-reported health (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance and ability to participate in social roles and activities) for the majority of people with chronic illness, each domain using a scale of a minimum score of 0 and a maximum score of 10. Derived T-score values are presented with higher scores equalling higher levels of the outcome being measured (e.g. more fatigue, more physical function). T-scores were calculated using the scoring service from the HealthMeasures Assessment Center. For this T-score metric 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.

Outcome measures

Measure	6-<12 Yrs n=31 Participants Age of patients	12-<17 Yrs n=31 Participants Age of patients	≥17 Yrs Age of patients	Total Total annualized bleeding rates in study WIL-31
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) Physical Function	47.63 T-score Standard Deviation 8.892	0.59 T-score Standard Deviation 5.457	—	—
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) Anxiety/Fear	49.64 T-score Standard Deviation 7.521	-1.47 T-score Standard Deviation 8.386	—	—
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) Depression/Sadness	46.97 T-score Standard Deviation 7.427	-2.15 T-score Standard Deviation 6.103	—	—
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) Fatigue	47.32 T-score Standard Deviation 9.408	-2.15 T-score Standard Deviation 8.658	—	—
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) Sleep Disturbances	45.35 T-score Standard Deviation 9.884	-1.21 T-score Standard Deviation 12.494	—	—
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) Ability to Participate in Social Roles/Activites	54.20 T-score Standard Deviation 9.310	0.97 T-score Standard Deviation 8.472	—	—
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) Pain Interference	51.04 T-score Standard Deviation 8.990	-3.65 T-score Standard Deviation 7.182	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

QoL assessment based on the results from the SF-36v2 (Short Form Health Survey) questionnaire to measure functional health and well-being in patients ≥16 years. SF-36v2 ranks 8 different domains using a scale standardized with a scoring algorithm to obtain a score ranging from 0 to 100. The eight health domains include physical functioning (PF), role physical (RP), bodily pain (BP), general health problems (GH), vitality (VT), social functioning (SF), role emotional (RE) and general mental health (MH). Norm-based scoring is used for the SF-36, setting the general population mean to 50 and the SD to 10 for all scales. Scores typically range from 20 to 60, with higher scores indicating better health.

Outcome measures

Measure	6-<12 Yrs n=18 Participants Age of patients	12-<17 Yrs n=18 Participants Age of patients	≥17 Yrs Age of patients	Total Total annualized bleeding rates in study WIL-31
Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2) Physical Component Scores	46.11 component scores Standard Deviation 10.572	3.58 component scores Standard Deviation 6.971	—	—
Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2) Mental Component Scores	50.08 component scores Standard Deviation 10.434	3.82 component scores Standard Deviation 9.887	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: Analysis based on number of completed SF-10 questionnaires completed for 6-15 year old children.

QoL assessment based on the results from a SF-10 parent-completed questionnaire for patients ≥6 and <16 years of age, in order to score physical and psychosocial health. Norm-based scoring is used for the SF-36, setting the general population mean to 50 and the SD to 10 for all scales. Scores typically range from 20 to 60, with higher scores indicating better health.

Outcome measures

Measure	6-<12 Yrs n=13 Participants Age of patients	12-<17 Yrs n=13 Participants Age of patients	≥17 Yrs Age of patients	Total Total annualized bleeding rates in study WIL-31
Quality of Life (QoL) Assessed Using a 10-Item Short Form Health Survey (SF-10) Physical Summary Score	40.59 derived scores Standard Deviation 10.907	6.06 derived scores Standard Deviation 13.141	—	—
Quality of Life (QoL) Assessed Using a 10-Item Short Form Health Survey (SF-10) Psychosocial Summary Score	50.15 derived scores Standard Deviation 7.161	-0.48 derived scores Standard Deviation 10.735	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 12 months

Joint health status will be assessed using the Hemophilia Joint Health Score (HJHS), which has been specifically validated for the assessment of the clinical outcome in VWD. HJHS evaluates six index joints to produce a score between 0-124. The maximum score for an individual index joint is 20. Higher scores indicate worse joint health.

Outcome measures

Measure	6-<12 Yrs n=9 Participants Age of patients	12-<17 Yrs n=6 Participants Age of patients	≥17 Yrs n=18 Participants Age of patients	Total n=33 Participants Total annualized bleeding rates in study WIL-31
Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) Total Score (12-month)	0.67 HJHS score Standard Deviation 2.000	2.67 HJHS score Standard Deviation 4.546	8.33 HJHS score Standard Deviation 20.780	4.90 HJHS score Standard Deviation 15.027
Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) Total Score (Baseline)	0.44 HJHS score Standard Deviation 0.882	2.83 HJHS score Standard Deviation 5.231	11.47 HJHS score Standard Deviation 19.622	6.75 HJHS score Standard Deviation 15.168
Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) Total Score (Change from Baseline)	0.22 HJHS score Standard Deviation 1.563	-0.17 HJHS score Standard Deviation 0.983	-4.33 HJHS score Standard Deviation 7.247	-2.13 HJHS score Standard Deviation 5.588

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Bleeding information from each menstrual period while in this study will be collected using the Pictorial Blood Loss Assessment Chart (PBAC). The PBAC will be provided to all female patients of child-bearing potential. The data documented in the PBAC and the investigator-calculated final score will be recorded in the electronic case report form (eCRF). The PBAC score is from 0 onwards, with no theoretical maximum. A score of >100 defines abnormal coagulation and heavy menstrual bleeding (>80ml of blood loss per menstrual cycle).

Outcome measures

Measure	6-<12 Yrs n=4 Participants Age of patients	12-<17 Yrs n=4 Participants Age of patients	≥17 Yrs Age of patients	Total Total annualized bleeding rates in study WIL-31
Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score	219.0 PBAC score Standard Deviation 91.71	143.5 PBAC score Standard Deviation 59.91	—	—

Adverse Events

Wilate

Serious events: 4 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Measure	Wilate n=43 participants at risk All patients who participated in the study and received at least 1 dose of Wilate were included in the analysis of adverse events
Reproductive system and breast disorders Menorrhagia	2.3% 1/43 • From patient enrolment to study completion [approximately 12 months]
Injury, poisoning and procedural complications Limb injury	2.3% 1/43 • From patient enrolment to study completion [approximately 12 months]
Gastrointestinal disorders Food poisoning	2.3% 1/43 • From patient enrolment to study completion [approximately 12 months]
Skin and subcutaneous tissue disorders Haemorrhodial haemorrhage	2.3% 1/43 • From patient enrolment to study completion [approximately 12 months]

Other adverse events

Measure	Wilate n=43 participants at risk All patients who participated in the study and received at least 1 dose of Wilate were included in the analysis of adverse events
Infections and infestations COVID-19 infection	7.0% 3/43 • From patient enrolment to study completion [approximately 12 months]
Infections and infestations Nasopharyngitis	4.7% 2/43 • From patient enrolment to study completion [approximately 12 months]
Infections and infestations Respiratory tract infection	11.6% 5/43 • From patient enrolment to study completion [approximately 12 months]
Immune system disorders Hypersensitivity	4.7% 2/43 • From patient enrolment to study completion [approximately 12 months]
Nervous system disorders Headache	16.3% 7/43 • From patient enrolment to study completion [approximately 12 months]
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	4.7% 2/43 • From patient enrolment to study completion [approximately 12 months]
Skin and subcutaneous tissue disorders Pruitus	4.7% 2/43 • From patient enrolment to study completion [approximately 12 months]
Musculoskeletal and connective tissue disorders Pain in extremity	4.7% 2/43 • From patient enrolment to study completion [approximately 12 months]
General disorders Pyrexia	4.7% 2/43 • From patient enrolment to study completion [approximately 12 months]
Investigations Parvovirus B19 test positive	4.7% 2/43 • From patient enrolment to study completion [approximately 12 months]

Additional Information

Dr. Sigurd Knaub, Senior VP CR&D Haematology

Octapharma

Phone: 01554512141

Email: Sigurd.Knaub@octapharma.com

Results disclosure agreements

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