A PHASE 3, OPEN-LABEL STUDY OF ALXN1210 IN CHILDREN AND ADOLESCENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)

Phase 3

Completed

Conditions: blood disorder
PNH
10018911

Registration Number: NL-OMON50200

Lead Sponsor: Alexion Pharmaceuticals

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 3

Inclusion Criteria

1. Male and female patients < 18 years of age and weighing * 5 kg at the time
of consent.
2. Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry
evaluation of red blood cells (RBCs) and white blood cells (WBCs), with
granulocyte or monocyte clone size of * 5%.
3. For patients not currently treated with complement inhibitor, presence of 1
or more of the following PNHrelated signs or symptoms within 3 months of
Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath
(dyspnea), anemia, history of a major adverse vascular event (including
thrombosis), dysphagia, or erectile dysfunction; or history of packed RBC
transfusion due to PNH.
4. Lactate dehydrogenase (LDH) values at Screening as follows:
a. For patients not currently treated with eculizumab, LDH level * 1.5 × upper
limit of normal (ULN).
b. For patients who are currently taking eculizumab, LDH * 1.5× ULN (sample
must be obtained on a
scheduled eculizumab-dosing day prior to dose administration [ie, at trough
eculizumab level] and
analyzed by the central laboratory).
5. To reduce the risk of meningococcal infection (Neisseria meningitidis), all
patients must be vaccinated against meningococcal infections within 3 years
prior to, or at the time of, initiating study drug. Patients who initiate study
drug treatment less than 2 weeks after receiving a meningococcal vaccine must
receive treatment with appropriate prophylactic antibiotics until 2 weeks after
vaccination. Patients who cannot be vaccinated must receive antibiotic
prophylaxis for the entire treatment period and for 8 months following last
dose.
6. Patients must have been vaccinated against Haemophilus influenzae type b
(Hib) and Streptococcus pneumoniae according to national and local vaccination
schedule guidelines, as appropriate.
7. Female patients of childbearing potential (ie, have achieved menarche) and
male patients with female partners of childbearing potential must follow
protocol-specified guidance for avoiding pregnancy while on treatment and for 8
months after last dose of study drug.
8. Patient's legal guardian must be willing and able to give written informed
consent and the patient must be willing to give written informed assent (if
applicable as determined by the central or local Institutional Review Board
[IRB]/Institutional (or Independent) Ethics Committee [IEC]) and comply with
the study visit schedule.

Exclusion Criteria

1. Platelet count < 30,000/mm3 (30 × 109/L) at Screening.
2. Absolute neutrophil count < 500/*L (0.5 × 109/L) at Screening.
3. History of bone marrow transplantation.
4. History of N. meningitidis infection.
5. History of unexplained, recurrent infection.
6. Active systemic bacterial, viral, or fungal infection within 14 days prior
to study drug administration on Day 1.
7. History of malignancy within 5 years of Screening with the exception of
adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix.
8. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic
disease (eg, active hepatitis) that, in the opinion of the Investigator or
Sponsor, precludes the patient*s participation in an
investigational clinical trial.
9. Unstable medical conditions (eg, myocardial ischemia, active
gastrointestinal bleed, severe congestive heart failure, anticipated need for
major surgery within 6 months of Screening, coexisting chronic anemia unrelated
to PNH) that would make them unlikely to tolerate the requirements of the
protocol.
10. Concomitant use of anticoagulants is prohibited if not on a stable regimen
for at least 2 weeks prior to Day 1.
11. History of hypersensitivity to any ingredient contained in the study drug,
including hypersensitivity to murine proteins.
12. Females who plan to become pregnant or are currently pregnant or
breastfeeding.
13. Females of childbearing potential who have a positive pregnancy test result
at Screening or on Day 1.
14. Participation in another interventional treatment 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.
15. Known or suspected history of drug or alcohol abuse or dependence within 1
year prior to the start of Screening.
16. Known medical or psychological condition(s) or risk factor that, in the
opinion of the Investigator or Sponsor, might interfere with the patient*s full
participation in the study, pose any additional risk for the patient, or
confound the assessment of the patient or outcome of the study.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoint:<br /><br>* PK/PD parameters (trough and peak) at Baseline and Weeks 2, 10, 18, and 26<br /><br>o PK: maximum serum concentration (Cmax), trough serum concentration (measured<br /><br>at end of dosing<br /><br>interval at steady state; Ctrough), accumulation ratio<br /><br>o PD: change in free C5 concentrations and in chicken red blood cell (cRBC)<br /><br>hemolytic activity over time</p><br>

Secondary Outcome Measures

Name	Time	Method