Efficacy of ALXN1210Sub-study: to Evaluate Patient Preference for the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH)
ID
Source
Brief title
Condition
- Red blood cell disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Hemolysis as directly measured by lactate dehydrogenase percent change
(LDH-PCHG)
Secondary outcome
- Change from baseline in quality of life (QoL) as assessed by the Functional
Assessment of Chronic Illness Therapy (FACIT)-Fatigue
- Percentage of patients who achieve transfusion avoidance (TA)
- Proportion of patients with stabilized hemoglobin
Background summary
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic disorder
that occurs most frequently in adults. The pathology and clinical presentations
in patients with PNH are driven by uncontrolled terminal complement activation
on red blood cells (RBCs).
The only approved treatment for PNH is eculizumab (Soliris®). Eculizumab is a
humanized monoclonal antibody that specifically binds to the complement protein
C5 with high affinity. ALXN1210 was engineered from eculizumab to preserve
immediate and complete C5 inhibition while providing sustained complement
inhibition throughout a prolonged dosing interval (1 month or longer). ALXN1210
and eculizumab share > 99% amino-acid sequence homology.
The main objective of effective PNH treatment with targeted therapy is to
provide immediate, complete, and sustained inhibition of terminal complement
activity to block hemolysis and prevent thrombosis. More specifically,
incomplete C5 blockade may increase risk of potentially life-threatening
breakthrough hemolysis (Hill 2012a, Lee 2013). Any loss of efficacy at the end
of a dosing interval or missed doses due to inconvenience of dosing intervals
may put patients at substantial medical risk. Patients treated with eculizumab
are required to receive maintenance infusions every 2 weeks. Given that PNH is
a chronic disease, this regimen may have a significant impact on patients in
terms of individual patient concerns associated with missed work and more
importantly may impact treatment compliance.
ALXN1210 has been designed to have the same rapid onset of action and effective
blockade of complement, with an increased serum half-life to yield an increased
duration of pharmacologic activity relative to eculizumab. The substantially
longer half-life of
ALXN1210 is expected to produce sustained terminal complement inhibition during
a longer dosing interval and thus reduce the potential risk of breakthrough
complement-mediated hemolysis during the treatment period, thus improving the
overall health of patients.
Study objective
Efficacy of ALXN1210
Sub-study: to Evaluate Patient Preference for the Treatment of Paroxysmal
Nocturnal Hemoglobinuria (PNH)
Study design
This is a Phase 3, open-label, randomized, active-controlled, multicenter
study.
Intervention
26-week randomized treatment period followed by an extension period in which
all patients will receive ALXN1210.
Study burden and risks
Potential risks associated with ALXN1210 include infections (N. meningitidis
and other encapsulated organisms), immunogenicity, and hypersensitivity.
Please refer to the IB, section 2.2 for a detailed description of Potential
Risks Associated with ALXN1210, Summary of Data, and Monitoring Guidance for
the Investigator.
Seaport Boulevard 121
Boston MA 2210
US
Seaport Boulevard 121
Boston MA 2210
US
Listed location countries
Age
Inclusion criteria
1. Male or female * 18 years of age
2. Treated with eculizumab for PNH for at least 6 months prior to Day 1
3. Lactate dehydrogenase (LDH) * 1.5 x upper limit of normal (ULN) at Screening
4. PNH diagnosis confirmed by documented by high-sensitivity flow cytometry
5. Documented meningococcal vaccination not more than 3 years prior to, or at
the time of, initiating study treatment.
6. Female patients of childbearing potential must use highly effective
contraception starting at screening and continuing until at least 8 months
after the last dose of ALXN1210
7. Willing and able to give written informed consent and comply with study
visit schedule
Exclusion criteria
1. History of bone marrow transplantation
2. Body weight < 40 kilograms
3. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic
disease that, in the opinion of the investigator or sponsor, would preclude
participation.
4. Unstable medical conditions (eg, myocardial ischemia, active
gastrointestinal bleed, severe congestive heart failure, anticipated need for
major surgery within 6 months of randomization, coexisting chronic anemia
unrelated to PNH)
5. Females who are pregnant, breastfeeding or who have a positive pregnancy
test at screening or Day 1
6. Participation in another interventional clinical study or use of any
experimental therapy within 30 days before initiation of study drug on
Day 1 in this study or within 5 half-lives of that investigational product,
whichever is greater.
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 | EUCTR2016-002026-36-NL |
| CCMO | NL60929.091.17 |