Paroxysmal Nocturnal HemoglobinuriaPhase 2NCT02605993
Open-label, Multiple Ascending Dose Study of Ravulizumab (ALXN1210) in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
A Phase 2 study testing Ravulizumab in people with Paroxysmal Nocturnal Hemoglobinuria and PNH, run by Alexion Pharmaceuticals, Inc. at 16 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria, PNH
- What is being tested?
- Ravulizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 16 sitesin 7 countries
- Study dates
- 4 Jan 2016to 12 Jan 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 7 countries.
16 sites in 7 countries
Spain4 sites
Clinical Trial Site
Badalona, Barcelona, 08916
Clinical Trial Site
Barcelona, 08036
Clinical Trial Site
Madrid, 28040
Clinical Trial Site
Majadahonda, Madrid, 28220
France3 sites
Clinical Trial Site
Lille, 59037
Clinical Trial Site
Lyon, Pierre-Bénite, 69495
Clinical Trial Site
Paris, 75475
Germany3 sites
Clinical Trial Site
Aachen, North Rhine-Westphalia, 52074
Clinical Trial Site
Essen, North Rhine-Westphalia, 45147
Clinical Trial Site
Ulm, Baden-Wurttemberg, 89081
South Korea2 sites
Clinical Trial Site
Seoul, 03080
Clinical Trial Site
Seoul, 03722
United Kingdom2 sites
Clinical Trial Site
Leeds, West Yorkshire, LS9 7TF
Clinical Trial Site
London, SE5 9RS
About this study
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
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.
Read the 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.
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria, PNH
- Being tested
- Ravulizumab
- Keywords
- complement inhibitor
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RavulizumabBiological
Also called ALXN1210, Ultomiris
All treatments were given as IV infusions.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 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. Receives: Biological: Ravulizumab |
| Cohort 2 | Experimental | 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. Receives: Biological: Ravulizumab |
| Cohort 3 | Experimental | 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. Receives: Biological: Ravulizumab |
| Cohort 4 | Experimental | 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. Receives: Biological: Ravulizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Secondary outcomes (6)
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.
Measured: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
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.
Measured: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
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.
Measured: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
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.
Measured: Baseline, Day 253 (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.
Measured: Baseline to Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
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.
Measured: Baseline, Day 253 (Cohorts 1 to 3) and Day 281 (Cohort 4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2015 (estimated)
- Study start4 Jan 2016
- Primary completion23 Feb 2017
- Study completion12 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Paroxysmal Nocturnal HemoglobinuriaStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02605993
- Sponsor's protocol ID
- ALXN1210-PNH-201
- Other IDs
- 2015-002674-20, 2015
- Status last verified
- Dec 2022
- First submitted
- 11 Nov 2015
- Last updated
- 4 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 30171081
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02605993
- Acronym / sponsor ID
- ALXN1210-PNH-201
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria, PNH
- Keywords
- complement inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 4 Jan 2016 (actual)
- Primary completion
- 23 Feb 2017 (actual)
- Study completion
- 12 Jan 2022 (actual)
- First posted
- 17 Nov 2015 (estimated)
- Results
- Posted 18 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: RavulizumabDuring 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. |
| Cohort 2 | Experimental | Biological: RavulizumabDuring 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. |
| Cohort 3 | Experimental | Biological: RavulizumabDuring 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. |
| Cohort 4 | Experimental | Biological: RavulizumabDuring 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RavulizumabAlso: ALXN1210, UltomirisAll treatments were given as IV infusions. | Biological | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
Primary outcome
Percent Change In LDH Levels From Baseline To Day 253 And Day 281
Time frame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
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.
6 secondary outcomes
Percent Change In Free Hemoglobin Levels From Baseline To Day 253 And Day 281
Time frame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Percent Change In Haptoglobin Levels From Baseline To Day 253 And Day 281
Time frame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 253 And Day 281
Time frame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Percent Change In PNH RBC Types II And III Clone Size From Baseline To Day 253
Time frame: Baseline, Day 253 (Cohorts 1 to 4)
Percent Change In D-dimer From Baseline To Day 253 And Day 281
Time frame: Baseline to Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Time frame: Baseline, Day 253 (Cohorts 1 to 3) and Day 281 (Cohort 4)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30171081Roth 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ravulizumab in people with Paroxysmal Nocturnal Hemoglobinuria and PNH, run by Alexion Pharmaceuticals, Inc. at 16 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Spain, France, Germany, South Korea, United Kingdom and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change In LDH Levels From Baseline To Day 253 And Day 281 (time frame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02605993, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2023.