Clinical trial NCT02598583: Dose-Escalation Study of ALXN1210 IV in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Official title: An Open-Label, Intrapatient, Dose-Escalation Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Patients With Paroxysmal Nocturnal Hemoglobinuria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: PNH
Keywords: Paroxysmal Nocturnal Hemoglobinuria
PNH
complement inhibitor
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-11-06
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: The data presented is up to the Primary Completion date of the study and is for the 24-week Primary Evaluation period. The study also includes an Extension Period of up to 5 years.

Eligibility criteria: Inclusion Criteria:

1. Male or female ≥18 years of age
2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry
3. Documented meningococcal vaccination not more than 3 years prior to dosing
4. 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
5. Willing and able to give written informed consent and comply with the study visit schedule

Exclusion Criteria:

1. Treatment with a complement inhibitor at any time
2. Females who were pregnant, breastfeeding or who had a positive pregnancy test at screening or Day 1
3. 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
4. History of allergy to excipients of ALXN1210 or known allergy to Chinese hamster ovary cell proteins
5. Inability to comply with study requirements
6. History of any clinically significant cardiac, hepatic, immunologic, pulmonary, or rheumatoid disease that, in the Investigator's judgment, would preclude participation
7. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, made the participant unsuitable for enrollment

Primary outcomes:
measure: Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169
timeFrame: Baseline, Day 169
Secondary outcomes:
measure: Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821
timeFrame: Baseline, Day 169, Day 1821
measure: Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821
timeFrame: Baseline, Day 169, Day 1821
measure: Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821
timeFrame: Baseline, Day 169, Day 1821
measure: Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933
timeFrame: Baseline, Day 169, Day 1933
measure: Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821
timeFrame: Baseline, Day 169, Day 1821
measure: Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821
timeFrame: Baseline, Day 169, Day 1821
measure: Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1
timeFrame: Day 1
measure: AUCt/ Dose-normalized (D) At Day 1
timeFrame: Day 1
measure: Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The End Of The Dosing Interval (AUCtau) At Day 141
timeFrame: Day 141
measure: AUCtau/D At Day 141
timeFrame: Day 141
measure: Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141
timeFrame: Day 1 and Day 141
measure: Cmax/D At Day 1 And Day 141
timeFrame: Day 1 and Day 141
measure: Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141
timeFrame: Day 1 and Day 141
measure: Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141
timeFrame: Day 1 and Day 141
measure: Percent Change In Chicken Red Blood Cell (cRBC) Hemolysis From Baseline To Day 1709
timeFrame: Baseline, Day 1709
measure: Percent Change In Free Complement Component 5 (C5) Concentration From Baseline To Day 1709
timeFrame: Baseline, Day 1709
measure: Percent Change In Total C5 Concentration From Baseline To Day 1709
timeFrame: Baseline, Day 1709
measure: Participants Experiencing Antidrug Antibodies (ADAs)
timeFrame: Day 1821
Other outcomes:
Locations:
city: Liverpool
country: Australia
facility: Clinical Trial Site
state: New South Wales
city: Woolloongabba
country: Australia
facility: Clinical Trial Site
state: Queensland
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Ulsan
country: Korea, Republic of
facility: Clinical Trial Site
Study officials:
affiliation: Alexion Pharmaceuticals, Inc.
name: Alexion Pharmaceuticals, Inc.
role: STUDY_DIRECTOR
References:
citation: Roth A, Rottinghaus ST, Hill A, Bachman ES, Kim JS, Schrezenmeier H, Terriou L, Urbano-Ispizua A, Wells RA, Jang JH, Kulasekararaj AG, Szer J, Aguzzi R, Damokosh AI, Shafner L, Lee JW. Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies. Blood Adv. 2018 Sep 11;2(17):2176-2185. doi: 10.1182/bloodadvances.2018020644.