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NCT02585960 | SNCTP000001930

Eine prospektive, randomisierte, multizentrische, klinische Studie der Phase 3 zum Vergleich der Sicherheit und Wirksamkeit von BAX 855 bei Patienten mit schwerer Hämophilie A

Data source: BASEC (Imported from 25.02.2020), WHO (Imported from 23.02.2020)
Changed: 14.02.2020
Disease category: Blutkrankheiten (nicht Krebs)

Brief description of trial (Source of data: BASEC)

Das Ziel dieser prospektiven, randomisierten, multizentrischen Phase-III-Studie ist der Vergleich der Sicherheit und Wirksamkeit zweier Dosierungsschemata eines Prüfpräparats mit der Bezeichnung BAX 855 hinsichtlich der Vorbeugung von Blutungen bei Patienten mit Hämophilie A. Die Studie wird weltweit mit 116 Patienten im Alter zwischen 12 und 65 Jahren an etwa 96 Prüfzentren durchgeführt. In der Schweiz nimmt nur ein Prüfzentrum in Zürich teil, das bestrebt ist, 2 Patienten in die Studie aufzunehmen. Es wird erwartet, dass die Teilnahme an dieser Studie 15–16 Monate dauert. In dieser Zeit nimmt der Patient mindestens 10 Termine im Prüfzentrum wahr und wird zweimal vom Prüfarzt angerufen. Das Prüfpräparat wird über eine Infusion in eine Vene (intravenös) verabreicht. Dies kann ein Kribbeln, Brennen, einen Bluterguss sowie eine Blutung oder Infektion an der Infusionsstelle zur Folge haben.

Health conditions investigated (Source of data: BASEC)

schwere Hämophilie A

Health conditions (Source of data: WHO)

Hemophilia A

Rare disease (Source of data: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Source of data: BASEC)

BAX855: PEGylierter rekombinanter Faktor VIII in voller Länge

Interventions (Source of data: WHO)

Biological: PEGylated Recombinant Factor VIII

Criteria for participation in trial (Source of data: BASEC)

1. Der Patient hat den Termin zum Studienende im Rahmen einer BAX-855-Studie abgeschlossen oder wechselt aus der laufenden Fortsetzungsstudie 261302.
2. Der Patient erhält die Behandlung mit BAX 855 entweder nach Bedarf oder zur Prophylaxe und hatte in den letzten 12 Monaten eine ABR mit ≥ 2 dokumentierten und behandelten Blutungen von ≥ 2.
3. Der Patient ist HIV (Humanes Immundefizienz-Virus)-negativ; oder der Patient ist HIV-positiv mit stabiler Erkrankung und einem vom Zentrallabor bestätigten (CD4+)-Zellzahl von ≥ 200 Zellen/mm3.
4. Der Patient ist willens und in der Lage, die Anforderungen des Prüfplans zu erfüllen

Exclusion criteria (Source of data: BASEC)

1. Der Patient hat inhibitorische Antikörper gegen FVIII mit einem Titer von ≥ 0,6 Bethesda-Einheiten (BE) entwickelt, was vom Zentrallabor im Verlauf der vorangegangenen BAX-855-Studie mit Hilfe der Nijmegen-Modifikation des Bethesda-Tests festgestellt wurde.
2. Bei dem Patienten wurde eine andere, erworbene hämostatische Störung als Hämophilie A diagnostiziert
3. Das Körpergewicht des Patienten liegt bei < 35 kg oder > 100 kg
4. Die Thrombozytenzahl des Patienten liegt bei < 100.000/ml
5. Der Patient hat eine auffällige Nierenfunktion (Serum-Kreatinin > 1,5 x obere Normgrenze [ONG])
6. Der Patient leidet an einer aktiven Lebererkrankung mit Alanin-Aminotransferase(ALT)- und/oder Aspartat-Aminotransferase(AST)-Spiegeln ≥ 5 x ONG
7. Für den Patienten ist während der Studie eine Behandlung mit einem anderen systemischen immunmodulierenden Präparat (z. B. kortikosteroide Wirkstoffe in einer Dosierung, die einer Hydrokortisongabe von mehr als 10 mg/Tag entspricht, oder α-Interferon) mit Ausnahme einer antiretroviralen Chemotherapie geplant
8. Der Patient leidet an einer klinisch signifikanten, medizinischen, psychiatrischen oder kognitiven Erkrankung oder konsumiert gelegentlich Drogen/Alkohol in einem Ausmass, das nach Einschätzung des Prüfarztes seine Sicherheit oder Compliance beeinträchtigen würde
9. Der Patient plant, im Verlauf der Studie an einer anderen klinischen Studie teilzunehmen
10. Der Patient ist ein Mitglied des Teams, das diese Studie durchführt, oder steht in einem Abhängigkeitsverhältnis zu einem Mitglied des Studienteams. Ein Abhängigkeitsverhältnis besteht sowohl bei nahen Verwandten (also Kindern, Partnern/Ehepartnern, Geschwistern, Eltern) als auch bei Angestellten des Prüfarztes oder Mitarbeitern des Prüfzentrums, die die Studie durchführen.

Inclusion/Exclusion Criteria (Source of data: WHO)


INCLUSION CRITERIA:

- Participants transitioning from another BAX 855 study who meet ALL of the following
criteria are eligible for this study:

1. Participant has completed the end of study visit of a BAX 855 study or is
transitioning from the ongoing Baxalta Continuation Study 261302.

2. Participant is either receiving on-demand treatment or prophylactic treatment
with BAX 855 and had an Annual Bleed Rate (ABR) of = 2 documented and treated
during the past 12 months.

3. Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable
disease and CD4+ count = 200 cells/mm^3, as confirmed by central laboratory.

4. Participant is willing and able to comply with the requirements of the protocol.

- Newly recruited participants (ie not transitioning from another BAX 855 study)
including BAX855 naïve participants who meet ALL of the following criteria are
eligible for this study:

1. Participant has severe hemophilia A (FVIII clotting activity < 1%) as confirmed
by central laboratory OR by historically documented FVIII clotting activity
performed by a certified clinical laboratory, optionally supported by a FVIII
gene mutation consistent with severe hemophilia A

2. Participant has been previously treated with plasma-derived FVIII concentrates or
recombinant FVIII for = 150 documented exposure days (EDs)

3. Participant is either receiving on-demand treatment or prophylactic treatment and
had an annual bleeding rate of = 2 documented and treated during the past 12
months.

4. Participant has a Karnofsky performance score of = 60 at screening

5. Participant is HIV-; or HIV+ with stable disease and CD4+ count = 200 cells/mm^3,
as confirmed by central laboratory at screening

6. Participant is hepatitis C virus negative (HCV-) by antibody (if positive,
additional PCR testing will be performed), as confirmed by central laboratory at
screening; or HCV+ with chronic stable hepatitis

7. If female of childbearing potential, participant presents with a negative urine
pregnancy test and agrees to employ adequate birth control measures for the
duration of the study

8. Participant is willing and able to comply with the requirements of the protocol.

EXCLUSION CRITERIA:

- Participants transitioning from another BAX 855 study who meet ANY of the following
criteria are not eligible for this study:

1. Participant has developed a confirmed inhibitory antibody to FVIII with a titer
of = 0.6 BU using the Nijmegen modification of the Bethesda assay as determined
at the central laboratory during the course of the previous BAX 855 study.

2. Participant has been diagnosed with an acquired hemostatic defect other than
hemophilia A.

3. The participant's weight is < 35 kg or > 100 kg.

4. Participant's platelet count is < 100,000/mL.

5. Participant has an abnormal renal function (serum creatinine > 1.5 times the
upper limit of normal).

6. Participant has active hepatic disease with alanine aminotransferase (ALT) and/or
aspartate aminotransferase (AST) levels = 5 times the upper limit of normal.

7. Participant is scheduled to receive a systemic immunomodulating drug (e.g.
corticosteroid agents at a dose equivalent to hydrocortisone greater than 10
mg/day, or a-interferon) other than anti-retroviral chemotherapy during the
study.

8. Participant has a clinically significant medical, psychiatric, or cognitive
illness, or recreational drug/alcohol use that, in the opinion of the
investigator, would affect participant's safety or compliance.

9. Participant is planning to take part in any other clinical study during the
course of the study.

10. Participant is a member of the team conducting this study or is in a dependent
relationship with one of the study team members. Dependent relationships include
close relatives (ie, children, partner/spouse, siblings, parents) as well as
employees of the investigator or site personnel conducting the study.

Newly recruited participants (ie not transitioning from another BAX 855 study) who meet ANY
of the following criteria are not eligible for this study:

1. Participant has detectable FVIII inhibitory antibodies (= 0.6 BU using the Nijmegen
modification of the Bethesda assay) as confirmed by central laboratory at screening.

2. Participant has a history of confirmed FVIII inhibitors with a titer = 0.6 Bethesda
Units (BU) (as determined by the Nijmegen modification of the Bethesda assay or the
assay employed with the respective cut-off in the local laboratory) at any time prior
to screening.

3. Participant has been diagnosed with an inherited or acquired hemostatic defect other
than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).

4. The participant's weight is < 35 kg or > 100 kg.

5. Participant's platelet count is < 100,000/mL.

6. Participant has known hypersensitivity towards mouse or hamster proteins, PEG or Tween
80.

7. Participant has severe chronic hepatic dysfunction [eg, = 5 times upper limit of
normal alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), as
confirmed by central laboratory at screening, or a documented INR > 1.5].

8. Participant has severe renal impairment (serum creatinine > 1.5 times the upper limit
of normal).

9. Participant has current or recent (< 30 days) use of other pegylated drugs prior to
study participation or is scheduled to use such drugs during study participation.

10. Participant is scheduled to receive during the course of the study, a systemic
immunomodulating drug (e.g. corticosteroid agents at a dose equivalent to
hydrocortisone greater than 10 mg/day, or a-interferon) other than anti-retroviral
chemotherapy.

11. Participant has participated in another clinical study involving an IP or
investigational device within 30 days prior to enrollment or is scheduled to
participate in another clinical study involving an IP or investigational device during
the course of this study.

12. Participant has a medical, psychiatric, or cognitive illness or recreational
drug/alcohol use that, in the opinion of the investigator, would affect participant
safety or compliance.

13. Participant is a member of the

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT02585960

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02585960

Further information on trial

Date trial registered

21.10.2015

Incorporation of the first participant

23.11.2015

Recruitment status

Completed

Academic title (Source of data: WHO)

Phase 3, Prospective, Randomized, Multi-center Clinical Study Comparing the Safety and Efficacy of BAX 855 Following PK-guided Prophylaxis Targeting Two Different FVIII Trough Levels in Subjects With Severe Hemophilia A

Type of trial (Source of data: WHO)

Interventional

Design of the trial (Source of data: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: None (Open Label).

Phase (Source of data: WHO)

Phase 3

Primary end point (Source of data: WHO)

Percentage of Participants With a Total Annualized Bleeding Rate (ABR) of Zero for Second Six Months

Secundary end point (Source of data: WHO)

Total Annualized Bleeding Rate for Second Six Months;Annualized Spontaneous Bleeding Rate for Second Six Months;Annualized Traumatic Bleeding Rate for Second Six Months;Annualized Joint Bleeding Rate (AJBR) for Second Six Months;Total Weight-adjusted Consumption of BAX 855;Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Number of Infusions;Number of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Bleed Resolution;Treatment of Bleeding Episodes: Number of BAX 855 Infusions Per Bleeding Episode Required Until Bleed Resolution;Change From Baseline in Hemophilia Joint Health Score (HJHS)- Total Score;Number of Participants With Hemostatic Efficacy Ratings for BAX 855 Treatment of Operative Bleeds;Blood Loss Per Participant in Case of Surgery;Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs);Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment Related Adverse Events;Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters Reported as Treatment Related Adverse Events;Number of Participants With Positive Inhibitory Antibodies and Binding Antibodies to Factor VIII (FVIII), BAX 855, Polyethylene Glycol (PEG), and Chinese Hamster Ovary (CHO) Protein;Change From Baseline in Physical Component Scores (PCS) of the Short Form-36 (SF-36) Health Survey;Area Under the Plasma Concentration of BAX 855 From Zero to Infinity (AUC0-inf);Incremental Recovery (IR) at Maximum Plasma Concentration (Cmax) of BAX 855;Plasma Half-life (T1/2) of BAX 855;Mean Residence Time (MRT) of BAX 855;Maximum Plasma Concentration (Cmax) of BAX 855;Time to Maximum Concentration of BAX 855 in Plasma (Tmax);Total Body Clearance (CL) of BAX 855;Volume of Distribution at Steady State (Vss);Incremental Recovery (IR) Over Time

Contact information (Source of data: WHO)

Please refer to primary and secondary sponsors

Trial sites

Trial sites in Switzerland (Source of data: BASEC)

Zürich

Countries (Source of data: WHO)

Australia, Austria, Bulgaria, Czech Republic, France, Germany, Hong Kong, Hungary, Israel, Italy, Malaysia, Norway, Poland, Romania, Singapore, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contact for further information on the trial

Details of contact in Switzerland (Source of data: BASEC)

Julia Funk
+497614541264
startupswitzerland@quintiles.com

Contact for general information (Source of data: WHO)

Study Director
Shire

Contact for scientific information (Source of data: WHO)

Study Director
Shire

Principal Sponsor/Investigator

Principal sponsor (Source of data: WHO)

Baxalta now part of Shire

Additional sponsors (Source of data : WHO)

Baxalta Innovations GmbH, now part of Shire

Further trial identification numbers

BASEC ID (Source of data: BASEC)

2016-00693

Secondary ID (Source of data: WHO)

2014-005477-37;261303