Back to resultsOpen-label, Multiple Ascending Dose Study of Ravulizumab (ALXN1210) in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Primary Purpose
Paroxysmal Nocturnal Hemoglobinuria, PNH
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ravulizumab
Sponsored by
About this trial
This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria focused on measuring 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 were to use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
- 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
- Female participants who are planning to become pregnant, or are 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 investigational product, whichever was greater
- History of allergy to any drug, allergen, excipients of ravulizumab 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, make 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
- 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 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Arm Description
During the Treatment Period, participants were administered ravulizumab 1400 milligram (mg) on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kilograms (kg), 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
Outcomes
Primary Outcome Measures
Percent Change In LDH Levels From Baseline To Day 253 And Day 281
The percent change in LDH levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Secondary Outcome Measures
Percent Change In Free Hemoglobin Levels From Baseline To Day 253 And Day 281
The percent change in free hemoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Percent Change In Haptoglobin Levels From Baseline To Day 253 And Day 281
The percent change in haptoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 253 And Day 281
The percent change in reticulocyte/erythrocyte count levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Percent Change In PNH RBC Types II And III Clone Size From Baseline To Day 253
The percent change in paroxysmal nocturnal hemoglobinuria (PNH) red blood cell (RBC), summed types II and III, clone size levels were assessed from Baseline to Day 253 for Cohorts 1 to 4.
Percent Change In D-dimer From Baseline To Day 253 And Day 281
The percent change in D-dimer levels were assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Clinical manifestations were assessed from Baseline to Day 253 for Cohorts 1 to 3 and from Baseline to Day 281 for Cohort 4 only. Clinical manifestations were defined as fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction (male participants only). Improvement was defined as present at Baseline and absent at Day endpoint. Worsening was defined as absent at Baseline and present at Day endpoint. No Change was defined as no change from Baseline and time point of endpoint.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02605993
Brief Title
Open-label, Multiple Ascending Dose Study of Ravulizumab (ALXN1210) in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
January 4, 2016 (Actual)
Primary Completion Date
February 23, 2017 (Actual)
Study Completion Date
January 12, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary purpose of this study is to evaluate the safety, tolerability, and efficacy of multiple intravenous (IV) doses of ravulizumab administered to complement inhibitor treatment-naïve participants with PNH.
Detailed Description
The study consisted of a screening period of up to 30 days and a Treatment Period of up to 253 days for Cohorts 1-3 and 281 days for Cohort 4. After completion of the Treatment Period, all participants had the opportunity to enter the Extension Period, wherein participants continue to receive ravulizumab for up to 5 years. The first dose in the Extension Period occurred on Day 253 for Cohorts 1-3 and on Day 281 for Cohort 4.
The data presented includes the Primary Completion date of the study for the Treatment Period. The results for the Extension Period will be reported after study completion.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria, PNH
Keywords
complement inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
During the Treatment Period, participants were administered ravulizumab 1400 milligram (mg) on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses.
In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kilograms (kg), 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses.
In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses.
In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses.
During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
Intervention Type
Biological
Intervention Name(s)
Ravulizumab
Other Intervention Name(s)
ALXN1210, Ultomiris
Intervention Description
All treatments were given as IV infusions.
Primary Outcome Measure Information:
Title
Percent Change In LDH Levels From Baseline To Day 253 And Day 281
Description
The percent change in LDH levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Time Frame
Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Secondary Outcome Measure Information:
Title
Percent Change In Free Hemoglobin Levels From Baseline To Day 253 And Day 281
Description
The percent change in free hemoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Time Frame
Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Title
Percent Change In Haptoglobin Levels From Baseline To Day 253 And Day 281
Description
The percent change in haptoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Time Frame
Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Title
Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 253 And Day 281
Description
The percent change in reticulocyte/erythrocyte count levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Time Frame
Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Title
Percent Change In PNH RBC Types II And III Clone Size From Baseline To Day 253
Description
The percent change in paroxysmal nocturnal hemoglobinuria (PNH) red blood cell (RBC), summed types II and III, clone size levels were assessed from Baseline to Day 253 for Cohorts 1 to 4.
Time Frame
Baseline, Day 253 (Cohorts 1 to 4)
Title
Percent Change In D-dimer From Baseline To Day 253 And Day 281
Description
The percent change in D-dimer levels were assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Time Frame
Baseline to Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Title
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Description
Clinical manifestations were assessed from Baseline to Day 253 for Cohorts 1 to 3 and from Baseline to Day 281 for Cohort 4 only. Clinical manifestations were defined as fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction (male participants only). Improvement was defined as present at Baseline and absent at Day endpoint. Worsening was defined as absent at Baseline and present at Day endpoint. No Change was defined as no change from Baseline and time point of endpoint.
Time Frame
Baseline, Day 253 (Cohorts 1 to 3) and Day 281 (Cohort 4)
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 were to use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
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
Female participants who are planning to become pregnant, or are 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 investigational product, whichever was greater
History of allergy to any drug, allergen, excipients of ravulizumab 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, make the participant unsuitable for enrollment
Facility Information:
Facility Name
Clinical Trial Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Clinical Trial Site
City
Lyon
State/Province
Pierre-Bénite
ZIP/Postal Code
69495
Country
France
Facility Name
Clinical Trial Site
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Clinical Trial Site
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Clinical Trial Site
City
Ulm
State/Province
Baden Wuerttemberg
ZIP/Postal Code
89081
Country
Germany
Facility Name
Clinical Trial Site
City
Aachen
State/Province
Nordrhein Westfalen
ZIP/Postal Code
52074
Country
Germany
Facility Name
Clinical Trial Site
City
Essen
State/Province
Nordrhein Westfalen
ZIP/Postal Code
45147
Country
Germany
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
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Clinical Trial Site
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28220
Country
Spain
Facility Name
Clinical Trial Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Clinical Trial Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Clinical Trial Site
City
Taipei City
ZIP/Postal Code
10048
Country
Taiwan
Facility Name
Clinical Trial Site
City
Leeds
State/Province
West Yorkshire
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Clinical Trial Site
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
12. IPD Sharing Statement
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
derived
Learn more about this trial
Open-label, Multiple Ascending Dose Study of Ravulizumab (ALXN1210) in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
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