A clinical trial to study Immunogenicity, Efficacy and Safety of Treatment with Human-cl rhFVIII in Previously Untreated Patients with Severe Haemophilia A

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2013/09/003958
• Date of registration: 05-09-2013
• Prospective Registration: Yes
• Primary sponsor: Octapharma AG
• Public title: A clinical trial to study Immunogenicity, Efficacy and Safety of Treatment with Human-cl rhFVIII in Previously Untreated Patients with Severe Haemophilia A
• Scientific title: Immunogenicity, Efficacy and Safety of Treatment with Human-cl rhFVIII in Previously Untreated Patients with Severe Haemophilia A
• Date of first enrolment: 17-02-2015
• Target sample size: 100
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=5646
• Study type: Interventional
• Study design: Single Arm Trial; Method of generating randomization sequence:Not Applicable Method of allocation concealment:Not Applicable Blinding and masking:Not Applicable
• Phase: Phase 3

Countries of recruitment

Belarus, Canada, France, Georgia, Germany, India, Italy, Morocco, Poland, Portugal, Republic of Moldova, Russian Federation, Slovenia, Spain, Ukraine, United Kingdom, United States of America

Contacts

• Name: Dr Shariq Anwar
• Affiliation: JSS Medical Research India Private Limited

• Name: Dr Sonika Newar
• Affiliation: JSS Medical Research India Private Limited

Key inclusion & exclusion criteria

Inclusion criteria: Subjects who fulfill the following criteria are eligible for inclusion into this study:



1. Male patients

2. Severe haemophilia A (FVIII: C < 1%)

3. No previous treatment with FVIII concentrates or other blood products containing FVIII

4. Voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted (obtained from the patientâ??s parent/legal guardian)
Exclusion criteria: 1. Diagnosis with a coagulation disorder other than haemophilia A

2. Severe liver or kidney disease (alanine amino transferase (ALT) or aspartate transaminase (AST) levels >5 times of upper limit of normal, creatinine >120 µmol/L)

3.Concomitant treatment with any systemic immunosuppressive drug

Participation in another interventional clinical study currently or during the past 4 weeks

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: D66- Hereditary factor VIII deficiency

Intervention(s)

Intervention1: Human-cl rhFVIII: Human-cl rhFVIII is a purified B-domain deleted FVIII glycoprotein that is synthesised by a genetically engineered human embryonic kidney cell line (HEK 293F). Human-cl rhFVIII will be provided in single use vials containing a nominal potency of 250, 500, 1000 or 2000 International Units (IU) each of freeze-dried recombinant FVIII (rFVIII) concentrate to be reconstituted in 2.5 mL of water for injection. 1Treatment is under the following modules: 1.Prophylactic treatment -Patients will be treated prophylactically with a recommended dose of 20-50 IU FVIII/kg body weight (BW) 2. On-demand treatment The dosage and duration of treatment of spontaneous or traumatic bleeds depend on the location and the extent of bleeding as well as on the clinical situation of the patient and the recommendations are given as follows: - Minor haemorrhage: 20-30 IU FVIII/kg BW to achieve intended target peak level of about 40-60 % - Moderate to major haemorrhage: 30-40 IU FVIII/kg BW to achieve an intended target peak level of about 60% to 80%. - Major to life-threatening haemorrhage: initial dose of 40-60 IU FVIII/kg BW to achieve an intended target peak level of 100% to 120%. 1. Surgical prophylaxis -Minor surgeries including tooth extractions: 25-30 IU FVIII/kg BW starting within 3 hours prior to surgery to achieve an intended target peak level of 30%. - Major surgeries: 40-60 IU FVIII/kg BW within 3 hours prior to surgery to achieve an intended target peak level of approximately 100%. 3. Recovery Investigation 4. Immune tolerance induction (ITI) (if applicable): Patients who develop a clinically significant and non-transient inhibitor will be offered to start ITI with the Investigational Medical Product (IMP). The modified Bonn Protocol for inhibitor elimin

Primary Outcome(s)

To investigate the immunogenicity of Human-cl rhFVIII in 100 previously

untreated patients (PUPs) suffering from severe Haemophilia A (FVIII:C less than 1%)

Timepoint: 1) At baseline (Screening Visit)

2) Every 3-4 EDs until ED 20

3) Every 10-12 EDs or every 3 months ± 2 weeks (whichever comes first) after ED 20

4) At study completion

5) Any time in the case of a suspicion of inhibitor development

Secondary Outcome(s)

â?¢ Assessment of the efficacy of Human-cl rhFVIII in surgical prophylaxis after the end of surgical prophylactic treatment phaseTimepoint: Efficacy will be assessed at the end of surgery by the surgeon and post-operatively by the surgeon and the haematologist

â?¢ Assessment of the efficacy of Human-cl rhFVIII during treatment of bleedsTimepoint: At the end of a BE, the following efficacy assessment will be made by the patientâ??s parent(s)/legal guardian(s) (together with the Investigator in case of on-site treatment

â?¢ Assessment of the efficacy of Human-cl rhFVIII during prophylactic treatment (based on the frequency of spontaneous break-through bleeds).Timepoint: The efficacy of Human-cl rhFVIII in prophylactic treatment will be evaluated based on the frequency of spontaneous breakthrough bleeds which means each time a breakthrough bleed occurs.

Secondary ID(s)

BB-IND 13722

2012-002554-23

GENA-05, , Protocol Version 5.0 dated 01 February 2018

Source(s) of Monetary Support

Octapharma AG Seidenstrasse 2 8853 Lachen Switzerland

Secondary Sponsor(s)

JSS Medical Research India Private Limited

Ethics review

Status: Approved
Approval date: 05/05/2018
Contact:

Ethics Committee- Silver office of Research, Christian Medical College

Status: Approved
Approval date: 05/05/2018
Contact:

Manipal University Ethics Committee, Manipal

Status: Approved
Approval date: 22/06/2018
Contact:

Sahyadri Hospitals Limited Ethics Committee

Results

• Date Completed: 22/06/2019