Primary objectives of the study are:• Arm 1 and Arm 3 (PTPs): to characterize the long-term safety profile of rVIII SingleChain with respect to inhibitor development in PTPs.• Arm 2 (PUPs): • To characterize the safety with respect to inhibitor…
ID
Source
Brief title
Condition
- Blood and lymphatic system disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure is the incidence rate of inhibitor formation to
FVIII over 100 EDs of rVIII-SingleChain in PTPs (Arm 1 and 3) and the incidence
of high-titer inhibitor formation over 50 EDs of rVIII-SingleChain in PUPs (Arm
2).
Treatment success for major bleeding episodes in PUPs.
Annualized spontaneous bleeding rate in PUPs.
Secondary outcome
• The rate of treatment success for bleeding episodes defined as a rating of
"excellent" or "good" on the investigator's clinical assessment of hemostatic
efficacy 4-point scale.
• The annualized bleeding rate (traumatic and non-traumatic) during prophylaxis
and on-demand treatment.
• The proportion of bleeding episodes requiring 1, 2, 3, or > 3 infusions of
rVIII-SingleChain to achieve hemostasis.
• The mean actual dose per kg per subject per year; the consumption of factor
VIII, expressed as number of infusions and IU/kg per month and per year, as
well as IU/kg per event (prophylaxis and ondemand).
• Investigator*s assessment of hemostatic efficacy of rVIII-SingleChain for
subjects who undergo surgery
Background summary
Hemophilia A is a rare but serious X-linked recessive bleeding disorder that
affects males and is characterized by a deficiency of clotting factor VIII
(FVIII). Individuals with severe hemophilia often bleed spontaneously, that is
without any known trauma or other cause.
This bleeding is predominantly into the joints and muscle.
Study objective
Primary objectives of the study are
:
• Arm 1 and Arm 3 (PTPs): to characterize the long-term safety profile of rVIII
SingleChain with respect to inhibitor development in PTPs.
• Arm 2 (PUPs):
• To characterize the safety with respect to inhibitor development in PUPs.
• To evaluate the efficacy of on-demand and prophylaxis treatment of rVIII
SingleChain in PUPs
The secondary objectives of the study are:
• Arm 1 and Arm 3 (PTPs):
• To characterize the safety profile of rVIII SingleChain with respect to
inhibitor development after 10 EDs and after 50 EDs
• To characterize the safety profile of rVIII SingleChain with respect to
antibodies against rVIII-SingleChain and antibodies to Chinese hamster ovary
(CHO) proteins
• To collect and evaluate efficacy information on the prophylaxis and treatment
of bleeding episodes
• To assess the hemostatic efficacy of rVIII-SingleChain for PTPs who undergo
surgery, using the 4-point efficacy evaluation of surgical treatment scale
• Arm 2 (PUPs):
• To further characterize the safety profile of rVIII SingleChain with respect
to inhibitor development
• To characterize the safety profile of rVIII SingleChain with respect to
antibodies against rVIII-SingleChain and antibodies to CHO proteinsTo collect
and evaluate the number of rVIII-SingleChain injections required for the
treatment of bleeding episodes
• To characterize consumption of rVIII-SingleChain in prophylaxis, on-demand
treatment, and surgery
• To assess the hemostatic efficacy of rVIII-SingleChain for PUPs who undergo
surgery, using the 4-point efficacy evaluation of surgical treatment scale
• To assess the occurrence of clinically significant abnormalities in vital
signs after rVIII-SingleChain administration
Study design
This will be an multicenter, nonrandomized, open-label, multiple-arm, phase 3
study.
All subjects will receive CSL627 as the study medication.
The study enrolls both subjects with and without previous exposure to factor
VIII (FVIII) replacement therapy in 1 of the following 3 arms:
1. Arm 1 (previously treated patients [PTPs]): subjects of all ages who have
participated in a previous CSL Behring (CSL)-sponsored study with rVIII
SingleChain.
2. Arm 2 (previously untreated patients [PUPs]): subjects 0 to <18 years of age
who have not been exposed previously to any FVIII product.
3. Arm 3*: PTPs < 65 years of age with at least 50 exposure days (EDs) to any
FVIII product and not currently enrolled in a rVIII SingleChain study.
A surgery substudy (open to all study arms) will investigate the use of
rVIII-SingleChain in surgery.
* Note: Arm 3 will remain closed until the sponsor determines to open it. Arm 3
will open in order to achieve a total of at least 200 PTPs for 100 EDs in Arms
1 and 3 combined. The sponsor will contact investigators directly when Arm 3 is
open for enrollment.
Intervention
rVIII-SingleChain is supplied as a lyophilized powder to be reconstituted with
diluent (Sterile Water for Injection / infusion). After reconstitution, rVIII
-SingleChain is administered as an IV infusion.
Study burden and risks
The benefits of treatment are stopping and/or preventing bleeding and enabling
a normal and longer life. Based on preclinical studies, CSL627 should be able
to deliver the same benefits seen with current FVIII treatments. In addition,
CSL627 should provide an adequate safety profile compared to other current
FVIII marketed products. The risks are that it might be less effective in
increasing factor VIII levels and stopping or preventing bleeding than current
products, and may correlate less well with clotting factor assays used by
clinicians. Treatment with any antihemophilic factor presents a risk of
inhibitor formation, although the absolute risk of inhibitor formation with
CSL627 is unknown.
The associated benefit of treatment with CSL627 outweighs any potential risks
for the subjects participating in this study.
Emil-von-Behring-Str. 76
Marburg 35041
DE
Emil-von-Behring-Str. 76
Marburg 35041
DE
Listed location countries
Age
Inclusion criteria
Eligible subjects will be males of any age who have been diagnosed with severe
hemophilia A (FVIII activity levels < 1%) and have participated in a previous
CSL-sponsored clinical study with rVIIISingleChain., Arm 1 (PTPs): subjects of
any age who have participated in a previous CSL-sponsored clinical study with
rVIII-SingleChain. , Arm 2 (PUPs): subjects 0 to < 18 years of age who have not
been exposed to any prior FVIII product (except for short-term use of blood
products)., Arm 3 (PTPs): subjects 0 to < 65 years of age who have had at least
50 EDs to a prior FVIII product and who are not currently enrolled in a
rVIII-SingleChain study, ITI substudy:
• PUPs who have developed a confirmed inhibitor to rVIII-SingleChain in the
main study.
Exclusion criteria
Subjects meeting any of the following exclusion criteria must not be enrolled
into the study:
• Currently receiving a therapy not permitted during the study, as defined in
Section 7.2 of the study protocol
• Previous participation in the current study
• Mental condition rendering the subject (or the subject's legally acceptable
representative[s]) unable to understand the nature, scope and possible
consequences of the study
• Known or suspected hypersensitivity to rVIII-SingleChain or to any
excipients of rVIII SingleChain or Chinese hamster ovary (CHO) proteins
• Any issue that, in the opinion of the investigator, would render the subject
unsuitable for participation in the study., • Known or suspected
hypersensitivity to rVIII SingleChain, to any excipients of rVIII SingleChain,
or to CHO proteins
• Currently receiving a therapy not permitted during the study
• Serum creatinine > 2 times the upper limit (x ULN), alnine aminotransferase
(ALT) or aspartate aminotransferase (AST) > 5 x ULN at Screening (if specified
for a particular arm)
• Any first-order family (eg, siblings) history of FVIII inhibitors
• Arm 3: Any history of or current FVIII inhibitors
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-003262-13-NL |
| CCMO | NL49424.018.14 |