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

September 27, 2021 updated by: Octapharma

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

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.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Córdoba, Argentina
        • Centro de Tratamiento de la Hemofilia Cordoba
      • Córdoba, Argentina
        • CTH Centro de Tratamiento de Hematologia y Hemoterapia Córdoba S.A.
      • Salta, Argentina
        • Fundación de Hemofilia de Salta
      • Santiago del Estero, Argentina
        • Centro Mayo
  • Belarus
      • Borovlyany, Belarus
        • Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
  • Czechia
      • Brno, Czechia
        • Fakultni Nemocnice Brno
      • Ostrava, Czechia
        • Blood Centre, University Hospital
  • Ecuador
      • Guayaquil, Ecuador, 090203
        • Hospital de Especialidades Teodoro Maldonado Carbo
  • France
      • Nantes, France
        • Chu Hotel Dieu
      • Rennes, France
        • Hôpital Pontchaillou
      • Saint-Priest-en-Jarez, France
        • CHRU Hôpital Nord
      • Toulouse, France
        • CRTH, Hopital Purpan
  • Guatemala
      • Guatemala, Guatemala
        • Pedias Inc. Centro Hospitalario La Paz
  • Italy
      • Bari, Italy
        • L'Azienda Ospedaliero Universitaria Consorziale Policlinico, U.O. di Medicina Trasfusionale, Centro Emofilia e Trombosi
      • Castelfranco Veneto, Italy
        • U.O.C. Ematologia, Ospedale San Giacomo Apostolo
      • Firenze, Italy
        • UOC Malattie emorragiche e della coagulazione, Azienda Ospedaliera Universitaria Careggi
      • Milan, Italy
        • Fondazione IRCCS Cà Granda
      • Naples, Italy
        • AOU Federico II - Dipartimento di Medicina Clinica e Chirurgica
      • Naples, Italy
        • Azienda Sanitaria Locale Napoli 1 Centro
      • Padova, Italy
        • Azienda Ospedaliera di Padova
      • Palermo, Italy
        • AOU Policlinico di Palermo
      • Palermo, Italy
        • Ospedale ARNAS Civico
      • Perugia, Italy
        • Dipartimento Di Medicina dell'Universita degli Studi di Perugia
      • Rome, Italy
        • Dipartimento di Biotecnologie Cellulari ed Ematologia -"Sapienza" Università di Roma
      • Torino, 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
  • Lithuania
      • Vilnius, Lithuania
        • Vilnius University Hospital, Santariskiu Klinikos-Children's Hospital
  • Norway
      • Oslo, Norway
        • Oslo University Hospital
  • Portugal
      • Covilhã, Portugal
        • Centro Hospitalar Cova da Beira
  • Slovakia
      • Bratislava, Slovakia
        • National Haemophilia Center
  • United Kingdom
      • London, United Kingdom
        • The Royal London Hospital
      • London, United Kingdom
        • St. Thomas' Hospital
      • London, United Kingdom
        • Great Ormond Street Hospital (GOSH)
      • Nottingham, United Kingdom
        • Nottingham University Hospitals NHS Trust
  • United States
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
      • Miami, Florida, United States, 33155
        • Nicklaus Children's Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University
    • Nevada
      • Las Vegas, Nevada, United States, 89109
        • Hemophilia Treatment Center of Nevada
    • Texas
      • Houston, Texas, United States, 77030
        • Gulf States Hemophilia and Thrombophilia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Sampling Method

Non-Probability Sample

Study Population

The goal is to collect data on 200 previously treated male patients of any age with haemophilia (FVIII:C ≤ 2%). Patients from pre-authorisation studies can be followed up to at least 100 EDs. Newly enrolled patients have to be treated and followed for at least 100 EDs.

  • Of the 200 enrolled patients, at least 100 patients should have severe haemophilia A (FVIII:C < 1%).
  • Of the 200 enrolled patients, approx. 60 patients should be < 12 years of age. At least 10 patients should be aged between 14-18 years.
  • Patients with severe haemophilia A after successful immune tolerance induction (ITI) can also be included; the proportion of these ITI patients should not exceed 25% of the entire cohort.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With FVIII Inhibitors
Time Frame: Screening through to study completion (minimum 1.7 months; maximum 31.6 months)
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)
Number of Patients With Adverse Drug Reactions
Time Frame: Recorded from screening through to study completion (minimum 1.7 months; maximum 31.6 months)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualized Rate of Breakthrough Bleeds to Assess Efficacy in Prophylactic Treatment
Time Frame: Monitored throughout the study from screening through to study completion (minimum 3.7 months; maximum 21.2 months)
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)
Assessment of the Efficacy of On-demand Treatment of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale
Time Frame: Monitored throughout the study from screening through to study completion (minimum 1.7 months; maximum 31.6 months)
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)
Overall Assessment of the Effectiveness of Surgical Prophylaxis by the Treating Physicians
Time Frame: From start of surgery until end of post-operative period
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
Assessment of the Efficacy of Treatment of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale
Time Frame: Recorded from screening through to study completion (minimum 1.7 months; maximum 31.6 months)

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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Octapharma

Investigators

  • Principal Investigator: Kate Khair, PhD, Great Ormond Street Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (Actual)

August 20, 2020

Study Completion (Actual)

August 20, 2020

Study Registration Dates

First Submitted

November 8, 2016

First Submitted That Met QC Criteria

November 9, 2016

First Posted (Estimate)

November 11, 2016

Study Record Updates

Last Update Posted (Actual)

October 21, 2021

Last Update Submitted That Met QC Criteria

September 27, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GENA-99

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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