A Phase 2, Open-Label, Multiple Ascending Dose Study to Evaluate the Efficacy, Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Patients with Paroxysmal Nocturnal Hemoglobinuria
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria (PNH)MedDRA version: 18.0Level: LLTClassification code 10055629Term: Paroxysmal nocturnal hemoglobinuriaSystem Organ Class: 100000004857Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2015-002674-20-SE
- Lead Sponsor
- Alexion Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 26
1. Male or female patients = 18 years of age
2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry (red blood cells [RBCs] and/or granulocytes)
3. Mean lactate dehydrogenase (LDH) =3 × upper limit of normal, based on 2 measurements from separate blood samples collected at least 1 day apart during screening
4. Willing and able to give written informed consent and comply with the study visit schedule
5. Documented meningococcal vaccination not more than 3 years prior to dosing
6. Female patients who consider themselves postmenopausal must provide evidence at screening of menopause status, based on a combination of amenorrhea for at least 1 year and increased serum follicle-stimulating hormone level (> 30 IU/L) on at least 2 occasions (eg, in the absence of hormone replacement therapy, dietary phytoestrogens) or estradiol concentration < 10 pg/mL.
7. Female patients of childbearing potential must use highly effective contraception as defined below, starting at screening and continuing until at least 6 months after the last dose of ALXN1210.
8. Male patients with a female spouse/partner of childbearing potential or a pregnant or breastfeeding spouse or partner must agree to use barrier contraception (male condom) during the Treatment Period and for at least 6 months after the last dose of ALXN1210. Barrier contraception is required even with documented medical assessment of surgical success of a vasectomy. Female spouses/partners of male patients who are of childbearing potential must use highly effective contraception or acceptable contraception, as defined below, starting at screening and continuing until at least 6 months after the last dose of ALXN1210. Male patients must not donate sperm during the
Screening and Treatment Periods and for at least 6 months after the last dose of ALXN1210.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3
1. Treatment with a complement inhibitor at any time
2. Platelet count < 30,000/mm3 (30 × 109 /L) at screening
3. Absolute neutrophil count < 500/µL (0.5 × 109 /L) at screening
4. History of bone marrow transplantation
5. History of Neisseria meningitidis infection; history of unexplained, recurrent infection; or infection requiring treatment with systemic antibiotics within the last 90 days prior to dosing on Day 1
6. Female patients who are planning to become pregnant, or are pregnant or breastfeeding
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy, safety, and tolerability of multiple doses of ALXN1210 administered intravenously (IV) to complement inhibitor treatment-naïve patients with PNH;Secondary Objective: The secondary objectives of the trial are:<br>- To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) effects of multiple doses of ALXN1210 administered IV to complement inhibitor treatment-naïve patients with PNH<br>- To investigate the immunogenicity of ALXN1210 administered IV to complement inhibitor treatment-naïve patients with PNH;Primary end point(s): Change in LDH levels from baseline to Day 253;Timepoint(s) of evaluation of this end point: Day 1, 7, 15, 22, 29, 43, 57, 85, 113, 127, 141, 169, 197, 211, 225, 253<br>
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Efficacy endpoints:<br>- Changes in hemolysis-related hematologic parameters<br>- Changes in clinical manifestations<br><br>Safety endpoints:<br>- Change from baseline in the need for blood transfusions<br>- Change from baseline in disease-associated biomarkers <br>- Change from baseline in quality of life<br>- Change from baseline in major adverse vascular events (MAVEs)<br><br>Immunogenicity: Measurement of antidrug antibodies (ADA)<br><br>Pharmacokinetic/Pharmacodynamic<br><br>Safety;Timepoint(s) of evaluation of this end point: Day 1, 7, 15, 22, 29, 43, 57, 85, 113, 127, 141, 169, 197, 211, 225, 253<br>