Primary Objective: The primary objective for this study is to evaluate the efficacy of ABP 959 compared with that of eculizumab based on control of intravascular hemolysis.Secondary Objective: The secondary objective is to assess the safety,…
ID
Source
Brief title
Condition
- Haematological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective for this study is to evaluate the efficacy of ABP 959
compared with that of eculizumab based on control of intravascular hemolysis.
Secondary outcome
The secondary objective is to assess the safety, pharmacokinetics (PK), and
immunogenicity of ABP 959 compared with that of eculizumab.
Background summary
ABP 959 is being developed as a *biosimilar* to eculizumab. This means that
there are no meaningful clinical differences in terms of safety, purity and
potency between the 2 products. The main difference between both drugs is that
eculizumab is already approved for this use and can be prescribed, whereas the
study drug ABP 959 cannot be prescribed yet because it is still being
investigated.
The active ingredient of ABP 959 is a monoclonal antibody similar to
eculizumab. Antibodies are made naturally in the body to defend against
infections or against other foreign proteins. Eculizumab inhibits the immune
system attacking the red blood cells.
Study objective
Primary Objective: The primary objective for this study is to evaluate the
efficacy of ABP 959 compared with that of eculizumab based on control of
intravascular hemolysis.
Secondary Objective: The secondary objective is to assess the safety,
pharmacokinetics (PK), and immunogenicity of ABP 959 compared with that of
eculizumab.
Study design
This is a randomized, double-blind, active-controlled, 2-period crossover study
in adult subjects with PNH. Approximately 40 subjects will be
randomized (1:1) to receive each investigational product in 1 of 2 sequences,
either treatment T followed by treatment R (TR) or treatment R followed by
treatment T (RT).
Treatment will be administered over 2 periods: Period 1 will be 52 weeks in
duration; Period 2 will start at week 53
with a crossover in treatment and will be 26 weeks in duration.
Period 1 (week 1 to week 53):
Treatment T: ABP 959 at a dose of 900 mg intravenously (IV) every 14 ± 2 days
for 52 weeks
Treatment R: eculizumab at a dose of 900 mg IV every 14 ± 2 days for 52 weeks
Period 2: (week 53 to week 79)
Treatment T: ABP 959 at a dose of 900 mg IV every 14 ± 2 days for 26 weeks
Treatment R: eculizumab at a dose of 900 mg IV every 14 ± 2 days for 26 weeks
Subjects may require dose adjustment (ie, increase dose to 1200 mg) within the
recommended 14 ± 2 day dosing schedule for investigational product based on
signs and symptoms of intravascular hemolysis, including lactate dehydrogenase
(LDH) levels.
Subjects will remain in the treatment phase until 14 days after the last
planned dose of investigational product in Period 2 (ie, at week 79).
An independent data monitoring committee (DMC) will evaluate the safety data
throughout the study.
Intervention
Period 1 (week 1 to week 53):
Treatment T: ABP 959 at a dose of 900 mg intravenously (IV) every 14 ± 2 days
for 52 weeks
Treatment R: eculizumab at a dose of 900 mg IV every 14 ± 2 days for 52 weeks
Period 2: (week 53 to week 79)
Treatment T: ABP 959 at a dose of 900 mg IV every 14 ± 2 days for 26 weeks
Treatment R: eculizumab at a dose of 900 mg IV every 14 ± 2 days for 26 weeks
Study burden and risks
Disadvantages of participation in the study may be
* possible side effects/risks/discomforts of the treatment and/or procedures of
the study;
* additional or longer hospital stays;
* additional tests;
* instructions to follow;
The information that is available on the possible side effects and/or risks of
ABP 959 or eculizumab, is based on reports received from other people during
their treatment with eculizumab. Since ABP 959 is a biosimilar, it is expected
to have the same or very similar side effects as eculizumab. However,
investigating the safety and side effects of ABP 959 is one of the main
purposes of this study.
More information about eculizumab (including side effects/risks) can be found
in the package leaflet of eculizumab..
The risks of ABP 959 and eculizumab on an unborn baby or a nursing infant are
not yet known. Therefore, women who are breastfeeding or pregnant or are
planning to become pregnant during the study or within 5 months after the last
dose of study drug cannot be included in the study.
It is not known, if the study medication can potentially cause damage to the
genetic material of the sperm, therefore male subjects should not father a
child during their participation in the study and within 5 months after their
last dose of study treatment. Subjects (including their partners) must use a
highly effective form of birth control during this study and for at least 5
months after the last administration of either ABP 959 or eculizumab.
Treatment may reduce the patients natural resistance to infections, especially
against certain organisms that cause meningitis (infection of the linings of
the brain). Serious meningococcal infections have occurred in patients treated
with eculizumab and may become rapidly life-threatening or result in death if
not recognized and treated early. Please consult the patients doctor before a
patient takes the study drug to be sure that the patient has received
vaccination against Neisseria meningitidis, an organism that causes meningitis.
The patient should have received this vaccination prior to starting the
eculizumab treatment. Please confirm with the patients doctor that the patients
current meningitis vaccination is up to date. Patients should also be aware
that vaccination may not prevent this type of infection. In accordance with
national recommendations, the patients doctor might consider that the patient
needs supplementary measures to prevent infection.
More information about the possible side effects and risks of ABP 959 or
eculizumab and possible risks related to the procedures of the study can be
found in appendix E of the ICF.
There may be risks or side effects related to the study drug or other study
procedures that are unknown at this time. In addition, there may be possible
side effects related to ABP 959 that are different from those of eculizumab
that are unknown at this time. Subjects will be informed in a timely manner if
new information on the study medication becomes available that may be relevant
to continued participation in the trial.
The study treatment may help patients in the treatment of PNH but this cannot
be guaranteed.
The efficacy and safety of eculizumab have been consistently shown in various
clinical studies. As a result, eculizumab is indicated for use in patients with
Paroxysmal Nocturnal Hemoglobinuria (PNH). Eculizumab is also approved for the
treatment of patients with atypical Haemolytic Uremic Syndrome (aHUS). The
current benefit-risk profile of ABP 959 is considered acceptable in the
proposed study because ABP 959 has been shown to be similar to eculizumab in
the quality analysis, pre-clinical and clinical phase 1 study, and the study
design for the phase 3 trial is in accordance with current standard of care and
is in line with current guidelines for the development of biosimilar medicines.
One Amgen Center Drive n/a
Thousand Oaks CA 91320-1799
US
One Amgen Center Drive n/a
Thousand Oaks CA 91320-1799
US
Listed location countries
Age
Inclusion criteria
The study will enroll subjects with PNH who are stable on eculizumab treatment.
Subjects cannot be enrolled or randomized before all inclusion criteria
(including test results) are confirmed:
1. Men and women * 18 years of age
2. Historical diagnosis of PNH by documented flow cytometry
3. Administration of eculizumab for * 6 months and currently receiving 900 mg
of eculizumab every 14 ± 2 days
4. Hemoglobin * 9.0 g/dL for at least 6 weeks prior to randomization
5. Lactate dehydrogenase (LDH) < 1.5 × the upper limit of normal at screening
6. Platelet count * 50 × 109/L
7. Absolute neutrophil count * 0.5 x 109/L (500/*L)
8. Subjects must be vaccinated against Neisseria meningitidis. Subjects must
have been vaccinated or revaccinated according to current national guidelines
for vaccination use.
9. Subjects must sign an institutional review board/independent ethics
committee-approved informed consent form before participation in any
procedures.
Exclusion criteria
If any of the following apply, the subject MUST NOT enter the study:
1. Known or suspected hereditary complement deficiency
2. Clinically significant cardiovascular disease (including myocardial
infarction, unstable angina, symptomatic congestive heart failure [New York
Heart Association * Class III], serious uncontrolled cardiac arrhythmia),
peripheral vascular disease, cerebrovascular accident, or transient ischemic
attack in the previous 6 months
3. Evidence of acute thrombosis (liver Doppler ultrasound of hepatic and portal
veins)
4. Known to be positive for human immunodeficiency virus
5. Woman who is pregnant or breastfeeding
6. Woman of childbearing potential who does not consent to use a highly
effective method of birth control (eg, true abstinence, sterilization, birth
control pills, Depo Provera injections, or contraceptive implants) during
treatment and for an additional 5 months after the last administration of
protocol-specified treatment
7. Man with a partner of childbearing potential who does not consent to use a
highly effective method of birth control (eg, true abstinence, vasectomy, or a
condom in combination with hormonal birth control or barrier methods used by
the woman) during treatment and for an additional 5 months after the last
administration of protocol-specified treatment
8. Subject is currently enrolled in or has not yet completed at least 30 days
since ending other investigational device or drug study(s), or subject is
receiving other investigational agent(s).
9. Subject has known sensitivity to any constituents of the products to be
administered during the study, including mammalian cell-derived drug products.
10. History or evidence of clinically significant disorder, infection,
condition, or disease that, in the opinion of the investigator or Amgen
physician, if consulted, would pose a risk to subject safety or interfere with
the study evaluation, procedures, or completion.
11. History of meningococcal infection
12. Presence or suspicion of active bacterial infection, or recurrent bacterial
infection.
13. History of bone marrow transplantation
14. Red blood cell transfusion required within 12 weeks before randomization
15. Subject experienced * 2 breakthrough events, (ie, signs and symptoms of
intravascular hemolysis, that require dose and/or schedule adjustments of
eculizumab) in the previous 12 months before screening.
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 | EUCTR2017-001418-27-NL |
| CCMO | NL62410.091.17 |