Paroxysmal Nocturnal Hemoglobinuria (PNH)Phase 2NCT03225287
Extension Study of RA101495 for Patients With PNH Who Have Completed a Zilucoplan (RA101495) Clinical Study
A Phase 2 study testing Zilucoplan (RA101495) in people with Paroxysmal Nocturnal Hemoglobinuria (PNH), run by Ra Pharmaceuticals, Inc. at 12 sites in 8 countries.
Trial summary
The purpose of this study is to enable continued access to zilucoplan (RA101495) for patients with paroxysmal nocturnal hemoglobinuria (PNH) after they complete a zilucoplan clinical study. 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?
- Zilucoplan (RA101495)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 12 sitesin 8 countries
- Study dates
- 17 Jul 2017to 26 Oct 2021
- 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
- Completion of a qualifying Ra Pharmaceuticals sponsored zilucoplan (RA101495) PNH study
- Evidence of ongoing clinical benefit in the opinion of the Investigator
Who cannot join
- History of meningococcal disease
- Current systemic infection or suspicion of active bacterial infection
Trial locations and contacts
12 sites in 8 countries.
12 sites in 8 countries
United States2 sites
Investigative Site 19
Dallas, Texas, 75390
Investigative Site 4
Los Angeles, California, 90033
New Zealand2 sites
Investigative Site 13
Christchurch
Investigative Site 12
Hamilton
United Kingdom2 sites
Investigative Site 6
Leeds
Investigative Site 7
London
About this study
Official title: A Multicenter, Open-label, Uncontrolled, Extension Study of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria Who Have Completed a RA101495 Clinical Study
The purpose of this study is to enable continued access to zilucoplan (RA101495) for patients with paroxysmal nocturnal hemoglobinuria (PNH) after they complete a zilucoplan clinical study.
- Being tested
- Zilucoplan (RA101495)
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zilucoplan (RA101495)Drug
Subjects will continue to receive the final maintenance dose they were receiving in the qualifying study.
| Study group | Role | What they receive |
|---|---|---|
| Zilucoplan (RA101495) | Experimental | Subjects will continue to receive the final maintenance dose they were receiving in the qualifying study Receives: Drug: Zilucoplan (RA101495) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAEs were defined as an AE that occurs after a participant's initial treatment zilucoplan start for this study (RA101495-01.202) that was not present at the time of treatment start, or an AE that increases in severity after treatment start in this study, if the event was present at the time of treatment start.
Measured: From Day 1 until the Final Study Visit (up to Month 49)
Percentage of Participants With Serious TEAEs
Serious Adverse event (SAE) was defined as any untoward medical occurrence that:• results in death, • is life-threatening threatening (note that this refers to an event in which the participant was at risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death if it were more severe), • requires hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, and • results in a congenital anomaly/birth defect.
Measured: From Day 1 until the Final Study Visit (up to Month 49)
Secondary outcomes (16)
Number of Participants With Anti-drug Antibodies (ADA)
Blood samples collection were planned to analyze for the presence/absence of ADAs to zilucoplan for immunogenicity assessments.
Measured: At Day 1, Month 1, 2, 3, 6, 9, and 12
Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point
Serum LDH levels were measure of intravascular hemolysis. As high level of LDH in the blood was indicative of hemolysis in participants with PNH.
Measured: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Change From Baseline in Total Bilirubin Values at Each Time Point
Total Bilirubin was monitored for signs and symptoms of hepatic or biliary dysfunction.
Measured: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Change From Baseline in Total Hemoglobin Values at Each Time Point
Total Hemoglobin Values were analyzed for hematology assessments.
Measured: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Change From Baseline in Free Hemoglobin Values at Each Time Point
Free Hemoglobin Values were analyzed for hematology assessments.
Measured: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Change From Baseline in Haptoglobin Values at Each Time Point
Haptoglobin values were analyzed for hematology assessments.
Measured: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Change From Baseline in Reticulocytes at Each Time Point
Reticulocytes values were analyzed for hematology assessments.
Measured: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Change From Baseline in Hemoglobinuria Values at Each Time Point
Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10 where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria.
Measured: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and Final Study Visit (Month 49)
Plasma Concentrations of RA101495 and Its Major Metabolite(s)
Blood samples of RA101495 (zilucoplan) and its metabolites (RA102758 and RA103488) were collected for Plasma concentration analysis.
Measured: Predose: At Day 1 (Screening), Month 1, 2, 3, 6, 9, 12, and Final Study Visit (Month 49)
Maximum Plasma Concentration (Cmax) of RA101495
Cmax is the maximum plasma concentration.
Measured: At Day 1, Month 1, 2, 3, 6, 9, and 12
Time Corresponding to Cmax (Tmax) of RA101495
tmax is the time to corresponding Cmax.
Measured: At Day 1, Month 1, 2, 3, 6, 9, and 12
Area Under the Drug Concentration-time Curve (AUC0-t) of RA101495
AUC0-t is area under the drug concentration-time curves.
Measured: At Day 1, Month 1, 2, 3, 6, 9, and 12
Total Complement (CH50) Levels
Blood samples collection were planned to assess complement (CH50) levels. The planned analysis of CH50 was not performed because the CH50 assay was not able to be validated due to lack of reproducibility of the manufacturer's kits.
Measured: At Day 1, Month 1, 2, 3, 6, 9, and 12
Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point
Blood samples were collected for measurement of sRBC lysis for the Classical Complement Pathways.
Measured: Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)
Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point
Blood samples were collected for measurement of membrane attack complex (MAC) by Wieslab ELISA for alternative complement pathway.
Measured: Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)
Change From Baseline in Complement Component 5 (C5) Values at Each Time Point
Blood samples were collected for measurement of Complement component 5 (C5) levels.
Measured: Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start17 Jul 2017
- Primary completion7 Sep 2021
- Study completion26 Oct 2021
Why it stopped: After careful consideration, UCB has decided to no longer pursue PNH as a potential indication for zilucoplan.
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 Hemoglobinuria (PNH)Studies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ra Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr. Anita Hill, Study chair, St James' Institute of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03225287
- Sponsor's protocol ID
- RA101495-01.202
- Other IDs
- 2016-003523-34, 2016
- Status last verified
- Sep 2023
- First submitted
- 17 Jul 2017
- Last updated
- 28 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
Publications
Kulasekararaj AG, Lehtinen AE, Forsyth C, Gandhi S, Griffin M, Korper S, Mikala G, Muus P, Overgaard U, Patriquin CJ, Pullon H, Shen YM, Spearing R, Szer J, De la Borderie G, Duda PW, Farzaneh-Far R, Ragunathan S, Sayegh CE, Vadysirisack DD, Schrezenmeier H. Phase II trials of zilucoplan in paroxysmal nocturnal hemoglobinuria. Haematologica. 2024 Mar 1;109(3):929-935. doi: 10.3324/haematol.2022.281780. No abstract available.
PubMed 37534517
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label, Uncontrolled, Extension Study of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria Who Have Completed a RA101495 Clinical Study
- ClinicalTrials.gov ID
- NCT03225287
- Acronym / sponsor ID
- RA101495-01.202
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: After careful consideration, UCB has decided to no longer pursue PNH as a potential indication for zilucoplan.
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Ra Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Jul 2017 (actual)
- Primary completion
- 7 Sep 2021 (actual)
- Study completion
- 26 Oct 2021 (actual)
- First posted
- 21 Jul 2017 (actual)
- Results
- Posted 27 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to enable continued access to zilucoplan (RA101495) for patients with paroxysmal nocturnal hemoglobinuria (PNH) after they complete a zilucoplan clinical study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zilucoplan (RA101495) | Experimental | Drug: Zilucoplan (RA101495)Subjects will continue to receive the final maintenance dose they were receiving in the qualifying study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Completion of a qualifying Ra Pharmaceuticals sponsored zilucoplan (RA101495) PNH study
- Evidence of ongoing clinical benefit in the opinion of the Investigator
Key exclusion criteria (2 listed)
- History of meningococcal disease
- Current systemic infection or suspicion of active bacterial infection
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 |
|---|---|---|
| Zilucoplan (RA101495)Subjects will continue to receive the final maintenance dose they were receiving in the qualifying study. | Drug | Zilucoplan (RA101495) |
Primary outcome
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: From Day 1 until the Final Study Visit (up to Month 49)
TEAEs were defined as an AE that occurs after a participant's initial treatment zilucoplan start for this study (RA101495-01.202) that was not present at the time of treatment start, or an AE that increases in severity after treatment start in this study, if the event was present at the time of treatment start.
Percentage of Participants With Serious TEAEs
Time frame: From Day 1 until the Final Study Visit (up to Month 49)
Serious Adverse event (SAE) was defined as any untoward medical occurrence that:• results in death, • is life-threatening threatening (note that this refers to an event in which the participant was at risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death if it were more severe), • requires hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, and • results in a congenital anomaly/birth defect.
16 secondary outcomes
Number of Participants With Anti-drug Antibodies (ADA)
Time frame: At Day 1, Month 1, 2, 3, 6, 9, and 12
Change From Baseline in Serum Lactate Dehydrogenase (LDH) Levels at Each Time Point
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Change From Baseline in Total Bilirubin Values at Each Time Point
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Change From Baseline in Total Hemoglobin Values at Each Time Point
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Change From Baseline in Free Hemoglobin Values at Each Time Point
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Change From Baseline in Haptoglobin Values at Each Time Point
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Change From Baseline in Reticulocytes at Each Time Point
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 49)
Change From Baseline in Hemoglobinuria Values at Each Time Point
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and Final Study Visit (Month 49)
Plasma Concentrations of RA101495 and Its Major Metabolite(s)
Time frame: Predose: At Day 1 (Screening), Month 1, 2, 3, 6, 9, 12, and Final Study Visit (Month 49)
Maximum Plasma Concentration (Cmax) of RA101495
Time frame: At Day 1, Month 1, 2, 3, 6, 9, and 12
Time Corresponding to Cmax (Tmax) of RA101495
Time frame: At Day 1, Month 1, 2, 3, 6, 9, and 12
Area Under the Drug Concentration-time Curve (AUC0-t) of RA101495
Time frame: At Day 1, Month 1, 2, 3, 6, 9, and 12
Total Complement (CH50) Levels
Time frame: At Day 1, Month 1, 2, 3, 6, 9, and 12
Change From Baseline in Sheep Red Blood Cell (sRBC) Values at Each Time Point
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)
Change From Baseline in Wieslab Enzyme-linked Immunosorbent Assay (ELISA) Values for Alternative Complement Pathway at Each Time Point
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)
Change From Baseline in Complement Component 5 (C5) Values at Each Time Point
Time frame: Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 49)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37534517Kulasekararaj AG, Lehtinen AE, Forsyth C, Gandhi S, Griffin M, Korper S, Mikala G, Muus P, Overgaard U, Patriquin CJ, Pullon H, Shen YM, Spearing R, Szer J, De la Borderie G, Duda PW, Farzaneh-Far R, Ragunathan S, Sayegh CE, Vadysirisack DD, Schrezenmeier H. Phase II trials of zilucoplan in paroxysmal nocturnal hemoglobinuria. Haematologica. 2024 Mar 1;109(3):929-935. doi: 10.3324/haematol.2022.281780. No abstract available.
- Individual participant dataSharing planned: Yes. Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
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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.
Dr. Anita Hill study chair
St James' Institute of Oncology
12 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zilucoplan (RA101495) in people with Paroxysmal Nocturnal Hemoglobinuria (PNH), run by Ra Pharmaceuticals, Inc. at 12 sites in 8 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 2 inclusion and 2 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: stopped early, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Australia, New Zealand, United Kingdom, Canada and 3 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 27 Oct 2022). 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?
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) (time frame: From Day 1 until the Final Study Visit (up to Month 49)). The study lists 2 primary outcomes in all. 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 NCT03225287, 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 28 Sep 2023.