The primary objective of the study is to evaluate the long-term safety, tolerability, and effect on intravascular hemolysis (ie, proportion ofpatients achieving lactate dehydrogenase (LDH) * 1.5× upper limit of normal (ULN) over 26 weeks) of…
ID
Source
Brief title
Condition
- Red blood cell disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary safety endpoint is incidence and severity of treatmentemergent
adverse events (TEAEs) and other safety variables during the
2-year open-label treatment period of the study in patients treated with
REGN3918.
The primary efficacy endpoint is the proportion of patients achieving LDH
*1.5×ULN over week 26, defined as LDH *1.5×ULN at every scheduled
time point up to week 26 (inclusive)
Secondary outcome
The secondary endpoints include:
*The proportion of patients with breakthrough hemolysis over week 26
*The rate and number of units of transfusion over week 26
Background summary
Eculizumab, approved for th e treatment of PNH in many countries worldwide, is
a humanized monoclonal antibody directed against
the terminal complement protein C5. It blocks the formation of the MAC -
C5b-9,thus protecting PNH RBCs from complementmediated
intravascular hemolysis. The basis for approval of eculizumab has been its
effectiveness in PNH, as evidenced by the initial reduction of lactate
dehydrogenase (LDH) levels and by the long-term reduction in the need for blood
transfusions; decrease
in the incidence of thrombosis; improvement in anemia; and improvement in
quality of life.
However, not all patients receive optimal therapeutic benefit. For example, 25%
of patients still need recurrent, albeit less frequent,
blood transfusions. Up to 20% of patients on eculizumab therapy require
significant increases in dose or dose freq uency due to breakthrough hemolysis
secondary to incomplete inhibition of
C5. In rare instances, eculizumab is ineffective due to polymorphic variation
in the gene encoding C5 such that the protein is not
recognized by eculizumab. The heterogeneity in these hematological responses
may be related to underlying aplastic anemia, C3bmediated
extravascular hemolysis, or incomplete pharmacologic blockade of C5, and rare
polymorphisms in the gene coding for C5.
Eculizumab administration every 2 weeks (Q2W) by intravenous (IV) in fusion has
been described as burdensome for patients.
REGN3918 is anticipated to provide better control of breakthrough hemolysis by
providing maximal and durable inhibition of C5
throughout the dosing interval, improving the dosing
regimen, binding to the polymorphic variant C5 prote in which renders
eculizumab ineffective, and development of a convenient
subcutaneous formulation.
Study objective
The primary objective of the study is to evaluate the long-term safety,
tolerability, and effect on intravascular hemolysis (ie, proportion of
patients achieving lactate dehydrogenase (LDH) * 1.5× upper limit of normal
(ULN) over 26 weeks) of REGN3918 in patients with paroxysmal
nocturnal hemoglobinuria (PNH).
The secondary objectives of the study are:
*To evaluate the long-term effect of REGN3918 on intravascular hemolysis.
*To assess the concentrations of total REGN3918 in serum.
*To evaluate the occurrence of the immunogenicity of REGN3918.
Study design
This study is an open-label study with REGN3918. Patients who have completed 1
of the 2 parent studies (ie, either R3918-PNH-1852
or R3918-PNH-1853) will be eligible for screening for this 2-year open label
extension (OLE) study.
This study contains 2 study periods: the 2-year open-label treatment period and
the optional post-end-of-treatment (EOT) period (ie, after completion of the
2-year open-label treatment period).
Intervention
Patients will be given a dose no greater than 800 mg subcutaneous (SC) QW (±1
day) over the treatment period.
Study burden and risks
-Additional visits to the hospital, additional physical tests, including a test
for gonnorhea and pregnancy.
-Possible rash or superficial irritation of the skin by the ECG stickers.
-In total about 225 ml blood will be taken, divided over 14 visits. This amount
won't cause any problems (to
compare: a blood donation involves 500ml of blood being taken each time).
Possible side effects of blood tests are fainting,
contusions, sore spot and sensitive area at the injection site and, in rare
cases, an infection.
Old Saw Mill River Road 777
Tarrytown 10591
US
Old Saw Mill River Road 777
Tarrytown 10591
US
Listed location countries
Age
Inclusion criteria
1. Patients with PNH who have completed, without discontinuation, study
treatment in one of the parent studies in which they participated
2. Willing and able to comply with clinic visits and study related procedures
3. Provide informed consent signed by study patient
Exclusion criteria
1. Significant protocol deviation(s) in the parent study based on the
investigator's judgment and to the extent that these would (if continued)
impact the study objectives and/or safety of the patient (for example,
repetitive non-compliance with dosing by the patient).
2. Any new condition or worsening of an existing condition which, in the
opinion of the investigator, would make the patient unsuitable for enrollment
or could interfere with the patient participating in or completing the study.
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 | EUCTR2019-000130-20-NL |
| CCMO | NL70621.091.19 |