Phase 2
N=13
Dose-Escalation Study of ALXN1210 IV in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
PNH
Bottom Line
View on ClinicalTrials.gov: NCT02598583 ↗Enrolled (actual)
13
Serious AEs
53.8%
Results posted
Jan 2018
Primary outcome: Primary: Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169 — -85.952; -84.736 percent change
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ALXN1210 (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Alexion Pharmaceuticals, Inc.
- Primary completion
- Jul 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169 |
-85.952; -84.736 | — |
| SECONDARY Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821 |
-22.335; -43.969; -35.062; 24.435 | — |
| SECONDARY Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821 |
40.0000; 17.1429; 72.0000; 62.5000 | — |
| SECONDARY Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821 |
-21.203; 28.784; -32.736; 9.763 | — |
| SECONDARY Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933 |
7.873; 25.840; 15.927; 13.960 | — |
| SECONDARY Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821 |
-27.42; -0.49; -12.74; 25.15 | — |
| SECONDARY Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 |
1; 1; 0; 0; 5; 6 | — |
| SECONDARY Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1 |
14273.95; 42366.62 | — |
| SECONDARY AUCt/ Dose-normalized (D) At Day 1 |
35.68; 70.61 | — |
| SECONDARY Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The End Of The Dosing Interval (AUCtau) At Day 141 |
216515.22; 217936.47 | — |
| SECONDARY AUCtau/D At Day 141 |
240.57; 242.15 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141 |
114.00; 203.50; 514.00; 512.25 | — |
| SECONDARY Cmax/D At Day 1 And Day 141 |
0.29; 0.34; 0.57; 0.57 | — |
| SECONDARY Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141 |
73.25; 80.50; 243.50; 204.00 | — |
| SECONDARY Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141 |
2.38; 1.88; 4.03; 2.40 | — |
| SECONDARY Percent Change In Chicken Red Blood Cell (cRBC) Hemolysis From Baseline To Day 1709 |
-72.316; -97.314 | — |
| SECONDARY Percent Change In Free Complement Component 5 (C5) Concentration From Baseline To Day 1709 |
-99.839; -99.802 | — |
| SECONDARY Percent Change In Total C5 Concentration From Baseline To Day 1709 |
65.852; 86.676 | — |
| SECONDARY Participants Experiencing Antidrug Antibodies (ADAs) |
0; 0 | — |
Summary
This study evaluated the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of multiple intravenous (IV) doses of ALXN1210 administered to participants with PNH who have not previously been treated with complement inhibitor.
Eligibility Criteria
Inclusion Criteria
- Male or female ≥18 years of age
- PNH diagnosis confirmed by documented high-sensitivity flow cytometry
- Documented meningococcal vaccination not more than 3 years prior to dosing
- Female participants of childbearing potential used highly effective contraception starting at screening and continuing until at least 24-weeks after the last dose of ALXN1210
- Willing and able to give written informed consent and comply with the study visit schedule
Exclusion Criteria
- Treatment with a complement inhibitor at any time
- Females who were pregnant, breastfeeding or who had a positive pregnancy test at screening or Day 1
- Participation in an interventional clinical study within 30 days before initiation of dosing on Day 1, or use of any experimental therapy within 30 days prior to dosing on Day 1, or within 5 half-lives of the product, whichever is greater
- History of allergy to excipients of ALXN1210 or known allergy to Chinese hamster ovary cell proteins
- Inability to comply with study requirements
- History of any clinically significant cardiac, hepatic, immunologic, pulmonary, or rheumatoid disease that, in the Investigator's judgment, would preclude participation
- Other unspecified reasons that, in the opinion of the Investigator or Sponsor, made the participant unsuitable for enrollment
Data sourced from ClinicalTrials.gov (NCT02598583). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.