Non-interventional Post-authorisation Study to Document the Immunogenicity, Safety, and Efficacy of NUWIQ

Hemophilia A Clinical Trial

Official title:

Prospective, Multinational, Non-interventional Post-authorisation Study to Document the Long-term Immunogenicity, Safety, and Efficacy of Human-cl rhFVIII (Simoctocog Alfa) in Patients With Haemophilia A Treated in Routine Clinical Practice

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02962765
• Other study ID #: GENA-99
• Status: Completed
• Start date: January 2015
• Est. completion date: August 20, 2020

Study information

• Verified date: September 2021
• Source: Octapharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Prospective, multinational, non-interventional post-authorisation study to collect additional clinical data and to ensure consistency in the long-term between the outcome from pre-authorisation clinical studies (in 135 previously treated paediatric and adult patients) and routine clinical practice. Besides aspects such as general product safety and efficacy, there will be a focus on immunogenicity, particularly on inhibitor development. The diagnosis of FVIII inhibitor will be based on clinical observations and confirmed by FVIII inhibitor testing in the laboratory.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: August 20, 2020
• Est. primary completion date: August 20, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Haemophilia A (FVIII:C = 2%) based on medical history; at least 100 patients should have severe haemophilia A (FVIII:C < 1%)

• Male patients of any age

• Previous treatment with a FVIII concentrate for more than 150 EDs

• Availability of detailed documentation (patient diary, log book, etc.) covering either the last 50 EDs or the last 2 years per patient to confirm treatment modality (i.e., prophylaxis, on-demand, recent surgery, or immune tolerance induction)

• Inhibitor negative (< 0.6 BU) at study entry as confirmed by a recovery test with previous FVIII product and inhibitor test in a central laboratory

• Immunocompetence (CD4+ count > 200/µL), HIV-negative, or having a viral load < 200 particles/µL or < 400,000 copies/mL

• Decision to prescribe Human-cl rhFVIII before enrolment into the study

• Written informed consent by the patient or the patient's parent or legal guardian

Exclusion Criteria:

• Patients treated with any investigational medicinal product (IMP) except FVIII IMP within 30 days prior to the Screening Visit or patients planning to undergo treatment with any IMP other than Human-cl rhFVIII are not eligible for enrolment into the study.

Related Conditions & MeSH terms

• Hemophilia A

Locations

Country	Name	City	State
Argentina	Centro de Tratamiento de la Hemofilia Cordoba	Córdoba
Argentina	CTH Centro de Tratamiento de Hematologia y Hemoterapia Córdoba S.A.	Córdoba
Argentina	Fundación de Hemofilia de Salta	Salta
Argentina	Centro Mayo	Santiago del Estero
Belarus	Belarusian Research Center for Pediatric Oncology, Hematology and Immunology	Borovlyany
Czechia	Fakultní nemocnice Brno	Brno
Czechia	Blood Centre, University Hospital	Ostrava
Ecuador	Hospital de Especialidades Teodoro Maldonado Carbo	Guayaquil
France	CHU Hôtel Dieu	Nantes
France	Hopital Pontchaillou	Rennes
France	CHRU Hôpital Nord	Saint-Priest-en-Jarez
France	CRTH, Hopital Purpan	Toulouse
Guatemala	Pedias Inc. Centro Hospitalario La Paz	Guatemala
Italy	L'Azienda Ospedaliero Universitaria Consorziale Policlinico, U.O. di Medicina Trasfusionale, Centro Emofilia e Trombosi	Bari
Italy	U.O.C. Ematologia, Ospedale San Giacomo Apostolo	Castelfranco Veneto
Italy	UOC Malattie emorragiche e della coagulazione, Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Fondazione IRCCS Ca Granda	Milan
Italy	AOU Federico II - Dipartimento di Medicina Clinica e Chirurgica	Naples
Italy	Azienda Sanitaria Locale Napoli 1 Centro	Naples
Italy	Azienda Ospedaliera di Padova	Padova
Italy	AOU Policlinico di Palermo	Palermo
Italy	Ospedale ARNAS Civico	Palermo
Italy	Dipartimento Di Medicina dell'Universita degli Studi di Perugia	Perugia
Italy	Dipartimento di Biotecnologie Cellulari ed Ematologia -"Sapienza" Università di Roma	Rome
Italy	A.O. Città della Salute e della Scienza di Torino - Ospedale Regina Margherita	Torino
Italy	S.C. Ematologia U, A.O.U. Città della Salute e della Scienza di Torino	Torino
Lithuania	Vilnius University Hospital, Santariskiu Klinikos-Children's Hospital	Vilnius
Norway	Oslo University Hospital	Oslo
Portugal	Centro Hospitalar Cova da Beira	Covilhã
Slovakia	National Haemophilia Center	Bratislava
United Kingdom	Great Ormond Street Hospital (GOSH)	London
United Kingdom	St. Thomas' Hospital	London
United Kingdom	The Royal London Hospital	London
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United States	University of Florida	Gainesville	Florida
United States	Gulf States Hemophilia and Thrombophilia	Houston	Texas
United States	Hemophilia Treatment Center of Nevada	Las Vegas	Nevada
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Tulane University	New Orleans	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Octapharma

Countries where clinical trial is conducted

United States,  Argentina,  Belarus,  Czechia,  Ecuador,  France,  Guatemala,  Italy,  Lithuania,  Norway,  Portugal,  Slovakia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With FVIII Inhibitors	FVIII inhibitors will be determined based on clinical observations and confirmed by FVIII inhibitor testing in the laboratory.	Screening through to study completion (minimum 1.7 months; maximum 31.6 months)
Primary	Number of Patients With Adverse Drug Reactions	Adverse drug reactions (ADRs) including hypersensitivity reactions will be recorded by patients in treatment diaries which will be reviewed at each Follow-up Visit.	Recorded from screening through to study completion (minimum 1.7 months; maximum 31.6 months)
Secondary	Annualized Rate of Breakthrough Bleeds to Assess Efficacy in Prophylactic Treatment	Total number of bleeding episodes under prophylaxis treatment divided by the duration of prophylactic phase (in years)	Monitored throughout the study from screening through to study completion (minimum 3.7 months; maximum 21.2 months)
Secondary	Assessment of the Efficacy of On-demand Treatment of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale	At the end of a BE, treatment efficacy was to be assessed either by the patient (or the patient's parent or legal guardian) or by the treating physician in case of on-site treatment using a 4-point scale including the four items 'excellent,' 'good,' moderate,' and 'none.' Excellent result was defined as abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection. Good was definite pain relief and/or improvement in signs of bleeding within approximately 8-12 hours after an injection requiring up to 2 injections for complete resolution. Moderate was probable or slight beneficial effect within approximately 12 hours after the first injection requiring more than two injections for complete resolution. None was no improvement after 12 hours, or worsening of symptoms, requiring more than 2 injections for complete resolution.	Monitored throughout the study from screening through to study completion (minimum 1.7 months; maximum 31.6 months)
Secondary	Overall Assessment of the Effectiveness of Surgical Prophylaxis by the Treating Physicians	At the end of the postoperative period, an overall assessment of the efficacy of treatment in the pre-, peri-, and postoperative periods using the 'excellent,' 'good,' moderate,' and 'none' scale will be done jointly by the surgeon and the hematologist. Based on this assessment, efficacy ratings assessed as either 'excellent' or 'good' will be considered 'successfully treated'.	From start of surgery until end of post-operative period
Secondary	Assessment of the Efficacy of Treatment of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale	At the end of a BE, treatment efficacy was to be assessed either by the patient (or the patient's parent or legal guardian) or by the treating physician in case of on-site treatment using a 4-point scale including the four items 'excellent', 'good', 'moderate', and 'none.'; Excellent result was defined as abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection. Good was definite pain relief and/or improvement in signs of bleeding within approximately 8-12 hours after an injection requiring up to 2 injections for complete resolution. Moderate was probable or slight beneficial effect within approximately 12 hours after the first injection requiring more than two injections for complete resolution. None was no improvement after 12 hours, or worsening of symptoms, requiring more than 2 injections for complete resolution.	Recorded from screening through to study completion (minimum 1.7 months; maximum 31.6 months)