Back to resultsDose-Escalation Study of ALXN1210 IV in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Primary Purpose
PNH
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ALXN1210
Sponsored by
About this trial
This is an interventional treatment trial for PNH focused on measuring Paroxysmal Nocturnal Hemoglobinuria, PNH, 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
Sites / Locations
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
- Clinical Trial Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Arm Description
Participants were administered ALXN1210 900 mg. In the Extension period participants continued at the same dose and frequency as the Primary Evaluation Period.
Participants were administered ALXN1210 1800 mg. In the Extension period participants continued at the same dose and frequency as the Primary Evaluation Period.
Outcomes
Primary Outcome Measures
Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169
Baseline was defined as the average of all available assessments prior to first ALXN1210 infusion.
Secondary Outcome Measures
Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821
Clinical manifestations are defined as fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction (ED) by cohort. Improvement is defined as present at baseline and absent at Day 169 endpoint. Worsening is defined as absent at Baseline and present at Day 169 endpoint.
Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1
AUCt reported in hours*microgram/milliliter (h*ug/mL).
AUCt/ Dose-normalized (D) At Day 1
Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The End Of The Dosing Interval (AUCtau) At Day 141
AUCtau/D At Day 141
Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141
Cmax/D At Day 1 And Day 141
Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141
Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141
Percent Change In Chicken Red Blood Cell (cRBC) Hemolysis From Baseline To Day 1709
Percent Change In Free Complement Component 5 (C5) Concentration From Baseline To Day 1709
Percent Change In Total C5 Concentration From Baseline To Day 1709
Participants Experiencing Antidrug Antibodies (ADAs)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02598583
Brief Title
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
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
November 12, 2015 (Actual)
Primary Completion Date
July 14, 2016 (Actual)
Study Completion Date
March 11, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PNH
Keywords
Paroxysmal Nocturnal Hemoglobinuria, PNH, complement inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Participants were administered ALXN1210 900 mg.
In the Extension period participants continued at the same dose and frequency as the Primary Evaluation Period.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Participants were administered ALXN1210 1800 mg.
In the Extension period participants continued at the same dose and frequency as the Primary Evaluation Period.
Intervention Type
Biological
Intervention Name(s)
ALXN1210
Intervention Description
Participants were administered ravulizumab as an IV infusion every 4 weeks.
Primary Outcome Measure Information:
Title
Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169
Description
Baseline was defined as the average of all available assessments prior to first ALXN1210 infusion.
Time Frame
Baseline, Day 169
Secondary Outcome Measure Information:
Title
Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821
Description
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time Frame
Baseline, Day 169, Day 1821
Title
Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821
Description
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time Frame
Baseline, Day 169, Day 1821
Title
Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821
Description
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time Frame
Baseline, Day 169, Day 1821
Title
Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933
Description
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time Frame
Baseline, Day 169, Day 1933
Title
Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821
Description
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time Frame
Baseline, Day 169, Day 1821
Title
Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821
Description
Clinical manifestations are defined as fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction (ED) by cohort. Improvement is defined as present at baseline and absent at Day 169 endpoint. Worsening is defined as absent at Baseline and present at Day 169 endpoint.
Time Frame
Baseline, Day 169, Day 1821
Title
Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1
Description
AUCt reported in hours*microgram/milliliter (h*ug/mL).
Time Frame
Day 1
Title
AUCt/ Dose-normalized (D) At Day 1
Time Frame
Day 1
Title
Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The End Of The Dosing Interval (AUCtau) At Day 141
Time Frame
Day 141
Title
AUCtau/D At Day 141
Time Frame
Day 141
Title
Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141
Time Frame
Day 1 and Day 141
Title
Cmax/D At Day 1 And Day 141
Time Frame
Day 1 and Day 141
Title
Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141
Time Frame
Day 1 and Day 141
Title
Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141
Time Frame
Day 1 and Day 141
Title
Percent Change In Chicken Red Blood Cell (cRBC) Hemolysis From Baseline To Day 1709
Time Frame
Baseline, Day 1709
Title
Percent Change In Free Complement Component 5 (C5) Concentration From Baseline To Day 1709
Time Frame
Baseline, Day 1709
Title
Percent Change In Total C5 Concentration From Baseline To Day 1709
Time Frame
Baseline, Day 1709
Title
Participants Experiencing Antidrug Antibodies (ADAs)
Time Frame
Day 1821
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexion Pharmaceuticals, Inc.
Organizational Affiliation
Alexion
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
Liverpool
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia
Facility Name
Clinical Trial Site
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Facility Name
Clinical Trial Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Clinical Trial Site
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Clinical Trial Site
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Clinical Trial Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Clinical Trial Site
City
Seoul
ZIP/Postal Code
06951
Country
Korea, Republic of
Facility Name
Clinical Trial Site
City
Ulsan
ZIP/Postal Code
44033
Country
Korea, Republic of
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.
Citations:
PubMed Identifier
30171081
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.
Results Reference
background
Links:
URL
https://www.ncbi.nlm.nih.gov/pubmed/?term=Ravulizumab+(ALXN1210)+in+patients+with+paroxysmal+nocturnal+hemoglobinuria%3A+results+of+2+phase+1b%2F2+studies
Description
Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies
Learn more about this trial
Dose-Escalation Study of ALXN1210 IV in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
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