Paroxysmal Nocturnal HemoglobinuriaPhase 2NCT03181633
A Long-Term Treatment Study of ACH-0144471 in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
A Phase 2 study testing ACH-0144471 in people with Paroxysmal Nocturnal Hemoglobinuria, run by Alexion Pharmaceuticals, Inc. at 4 sites in 3 countries.
Trial summary
The purpose of this study is to evaluate the long-term safety and efficacy of ACH-0144471 in participants with paroxysmal nocturnal hemoglobinuria (PNH) who have demonstrated clinical benefit from ACH-0144471 in Study ACH471-100. This study is designed to include up to 12 participants. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria
- What is being tested?
- ACH-0144471
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 22 Jun 2017to 4 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
- Study designed to include up to 12 participants who completed treatment in Study ACH471-100 and demonstrated clinical benefit from ACH-0144471 with no significant safety or tolerability concerns.
- Negative pregnancy test for females prior to dosing and throughout the study.
Who cannot join
- Have developed any clinically relevant co-morbidities while participating in Study ACH471-100 that would make the participant inappropriate for the continuation of treatment with ACH-0144471, in the opinion of the Investigator.
- Have developed any clinically significant laboratory abnormalities while participating in Study ACH471-100 that, in the opinion of the Investigator, would make the participant inappropriate for the study or put the participant at undue risk.
- Females who are pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration or participants with a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration.
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
About this study
Official title: An Open-Label Study to Evaluate Efficacy and Safety of Long-Term Treatment With ACH-0144471 in Participants Who Completed Clinical Study ACH471-100
The purpose of this study is to evaluate the long-term safety and efficacy of ACH-0144471 in participants with paroxysmal nocturnal hemoglobinuria (PNH) who have demonstrated clinical benefit from ACH-0144471 in Study ACH471-100. This study is designed to include up to 12 participants.
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Being tested
- ACH-0144471
- Keywords
- PNH, Paroxysmal, Hemoglobinuria, ACH-0144471, ALXN2040, Danicopan
- Medical subject headings
- Hemoglobinuria, Paroxysmal, Hemoglobinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACH-0144471Drug
ACH-0144471 will be administered to all participants enrolled in the study.
| Study group | Role | What they receive |
|---|---|---|
| ACH-0144471 | Experimental | All participants will receive ACH-0144471 during the treatment period. Receives: Drug: ACH-0144471 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in LDH Level at Week 25
Change from Baseline = Serum LDH levels at Week 25 - Baseline Serum LDH levels. Baseline was the baseline value from the primary Study ACH471-100.
Measured: Baseline, Week 25
Change From Baseline in Hgb Level in the Absence of RBC Transfusion at Week 25
Change from Baseline = Hgb levels at Week 25 - Baseline Hgb levels. Baseline was the baseline value from the primary Study ACH471-100.
Measured: Baseline, Week 25
Change From Baseline in Reticulocyte Counts at Week 25
Change from Baseline = reticulocyte count at Week 25 - Baseline reticulocyte count. Baseline was the baseline value from the primary Study ACH471-100.
Measured: Baseline, Week 25
Number of RBC Units Transfused
Measured: Baseline up to Week 169
Number of RBC Transfusion Instances
Measured: Baseline up to Week 169
Change From Baseline in PNH Clone Size at Week 25
The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Change from Baseline = PNH clone size at Week 25 - Baseline PNH clone size. Baseline was the baseline value from the primary Study ACH471-100.
Measured: Baseline, Week 25
Change From Baseline in AP Complement Functional Activity at Week 25
Serum AP functional activity was measured by the Wieslab functional immunoassay method. Change from Baseline = Serum AP functional activity at Week 25 - Baseline Serum AP functional activity. Baseline was the baseline value from the primary Study ACH471-100.
Measured: Baseline, Week 25
Change From Baseline in Free Hgb at Week 25
Change from Baseline = free Hgb at Week 25 - Baseline free Hgb. Baseline was the baseline value from the primary Study ACH471-100.
Measured: Baseline, Week 25
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Grade 3 and Grade 4 Adverse Events (AEs), And AEs Leading To Discontinuation
An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. The intensity of an AE was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Adverse Event Severity Grading Table. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Measured: Baseline up to 4.5 years
Secondary outcomes (8)
Change From Baseline in LDH Level at Weeks 49 and 169
Change from Baseline = Serum LDH levels at specified postbaseline visit - Baseline Serum LDH levels. Baseline was the baseline value from the primary Study ACH471-100.
Measured: Baseline, Weeks 49 and 169
Change From Baseline in Hgb Level in the Absence of RBC Transfusion at Weeks 49 and 169
Change from Baseline = Hgb levels at specified postbaseline visit - Baseline Hgb levels. Baseline was the baseline value from the primary Study ACH471-100.
Measured: Baseline, Weeks 49 and 169
Change From Baseline in Reticulocyte Counts at Weeks 49 and 169
Change from Baseline = reticulocyte count at specified postbaseline visit - Baseline reticulocyte count. Baseline was the baseline value from the primary Study ACH471-100.
Measured: Baseline, Weeks 49 and 169
Change From Baseline in PNH Clone Size at Weeks 49 and 73
The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Change from Baseline = PNH clone size at specified postbaseline visit - Baseline PNH clone size. Baseline was the baseline value from the primary Study ACH471-100.
Measured: Baseline, Weeks 49 and 73
Change From Baseline in AP Complement Functional Activity at Weeks 49 and 145
Serum AP functional activity was measured by the Wieslab functional immunoassay method. Change from Baseline = Serum AP functional activity at specified postbaseline visit - Baseline Serum AP functional activity. Baseline was the baseline value from the primary Study ACH471-100.
Measured: Baseline, Weeks 49 and 145
Change From Baseline in Free Hgb at Weeks 49 and 169
Change from Baseline = free Hgb at specified postbaseline visit - Baseline free Hgb. Baseline was the baseline value from the primary Study ACH471-100.
Measured: Baseline, Weeks 49 and 169
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at Weeks 21, 41, and 153
The FACIT-Fatigue scale is a collection of quality of life questionnaires pertaining to the management of fatigue symptoms due to a chronic illness. The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days. Participants score each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores range from 0 to 52, with higher score indicating better quality of life.
Measured: Baseline, Weeks 21, 41, and 153
Change From Baseline in European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 Scale (EORTC-QLQ-C30): Global Health Status/Qol Score at Weeks 21, 41, and 153
EORTC-QLQ-C30 is comprised of 30 questions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) \& other single items. For each item, high score = high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health (global health status) and quality of life, coded on 7-point scale (1=very poor to 7=excellent). Answers were converted into grading scale, with total score between 0 and 100. A high score represented a favourable outcome with a best quality of life for participant.
Measured: Baseline, Weeks 21, 41, and 153
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2017
- Study start22 Jun 2017
- Primary completion4 Jan 2022
- Study completion4 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Achillion, a wholly owned subsidiary of Alexion
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03181633
- Sponsor's protocol ID
- ACH471-103
- Other IDs
- 2017-000665-79, U1111-1196-0653, 2017
- Status last verified
- Feb 2023
- First submitted
- 5 Jun 2017
- Last updated
- 14 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kulasekararaj A, Browett P, Risitano AM, Patriquin CJ, Yenerel MN, Marceau D, Sahin F, Algarra JL, Ogawa M, Yu J, Cross NB, Notaro R, Lee JW, Brodsky RA. Efficacy and safety of vemircopan as monotherapy in patients with paroxysmal nocturnal hemoglobinuria. Blood Adv. 2026 Feb 10;10(3):540-554. doi: 10.1182/bloodadvances.2025017731.
PubMed 41124654
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Evaluate Efficacy and Safety of Long-Term Treatment With ACH-0144471 in Participants Who Completed Clinical Study ACH471-100
- ClinicalTrials.gov ID
- NCT03181633
- Acronym / sponsor ID
- ACH471-103
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Keywords
- PNH, Paroxysmal, Hemoglobinuria, ACH-0144471, ALXN2040, Danicopan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Achillion, a wholly owned subsidiary of Alexion
- Study start
- 22 Jun 2017 (actual)
- Primary completion
- 4 Jan 2022 (actual)
- Study completion
- 4 Jan 2022 (actual)
- First posted
- 9 Jun 2017 (actual)
- Results
- Posted 14 Mar 2023
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 evaluate the long-term safety and efficacy of ACH-0144471 in participants with paroxysmal nocturnal hemoglobinuria (PNH) who have demonstrated clinical benefit from ACH-0144471 in Study ACH471-100. This study is designed to include up to 12 participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ACH-0144471 | Experimental | Drug: ACH-0144471All participants will receive ACH-0144471 during the treatment period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Study designed to include up to 12 participants who completed treatment in Study ACH471-100 and demonstrated clinical benefit from ACH-0144471 with no significant safety or tolerability concerns.
- Negative pregnancy test for females prior to dosing and throughout the study.
Key exclusion criteria (3 listed)
- Have developed any clinically relevant co-morbidities while participating in Study ACH471-100 that would make the participant inappropriate for the continuation of treatment with ACH-0144471, in the opinion of the Investigator.
- Have developed any clinically significant laboratory abnormalities while participating in Study ACH471-100 that, in the opinion of the Investigator, would make the participant inappropriate for the study or put the participant at undue risk.
- Females who are pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration or participants with a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration.
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 |
|---|---|---|
| ACH-0144471ACH-0144471 will be administered to all participants enrolled in the study. | Drug | ACH-0144471 |
Primary outcome
Change From Baseline in LDH Level at Week 25
Time frame: Baseline, Week 25
Change from Baseline = Serum LDH levels at Week 25 - Baseline Serum LDH levels. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in Hgb Level in the Absence of RBC Transfusion at Week 25
Time frame: Baseline, Week 25
Change from Baseline = Hgb levels at Week 25 - Baseline Hgb levels. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in Reticulocyte Counts at Week 25
Time frame: Baseline, Week 25
Change from Baseline = reticulocyte count at Week 25 - Baseline reticulocyte count. Baseline was the baseline value from the primary Study ACH471-100.
Number of RBC Units Transfused
Time frame: Baseline up to Week 169
Number of RBC Transfusion Instances
Time frame: Baseline up to Week 169
Change From Baseline in PNH Clone Size at Week 25
Time frame: Baseline, Week 25
The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Change from Baseline = PNH clone size at Week 25 - Baseline PNH clone size. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in AP Complement Functional Activity at Week 25
Time frame: Baseline, Week 25
Serum AP functional activity was measured by the Wieslab functional immunoassay method. Change from Baseline = Serum AP functional activity at Week 25 - Baseline Serum AP functional activity. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in Free Hgb at Week 25
Time frame: Baseline, Week 25
Change from Baseline = free Hgb at Week 25 - Baseline free Hgb. Baseline was the baseline value from the primary Study ACH471-100.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Grade 3 and Grade 4 Adverse Events (AEs), And AEs Leading To Discontinuation
Time frame: Baseline up to 4.5 years
An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. The intensity of an AE was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Adverse Event Severity Grading Table. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
8 secondary outcomes
Change From Baseline in LDH Level at Weeks 49 and 169
Time frame: Baseline, Weeks 49 and 169
Change From Baseline in Hgb Level in the Absence of RBC Transfusion at Weeks 49 and 169
Time frame: Baseline, Weeks 49 and 169
Change From Baseline in Reticulocyte Counts at Weeks 49 and 169
Time frame: Baseline, Weeks 49 and 169
Change From Baseline in PNH Clone Size at Weeks 49 and 73
Time frame: Baseline, Weeks 49 and 73
Change From Baseline in AP Complement Functional Activity at Weeks 49 and 145
Time frame: Baseline, Weeks 49 and 145
Change From Baseline in Free Hgb at Weeks 49 and 169
Time frame: Baseline, Weeks 49 and 169
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at Weeks 21, 41, and 153
Time frame: Baseline, Weeks 21, 41, and 153
Change From Baseline in European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 Scale (EORTC-QLQ-C30): Global Health Status/Qol Score at Weeks 21, 41, and 153
Time frame: Baseline, Weeks 21, 41, and 153
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41124654Kulasekararaj A, Browett P, Risitano AM, Patriquin CJ, Yenerel MN, Marceau D, Sahin F, Algarra JL, Ogawa M, Yu J, Cross NB, Notaro R, Lee JW, Brodsky RA. Efficacy and safety of vemircopan as monotherapy in patients with paroxysmal nocturnal hemoglobinuria. Blood Adv. 2026 Feb 10;10(3):540-554. doi: 10.1182/bloodadvances.2025017731.
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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.
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ACH-0144471 in people with Paroxysmal Nocturnal Hemoglobinuria, run by Alexion Pharmaceuticals, Inc. at 4 sites in 3 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 3 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 14 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy, New Zealand, South Korea. 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 14 Mar 2023). 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?
Change From Baseline in LDH Level at Week 25 (time frame: Baseline, Week 25). The study lists 9 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 NCT03181633, 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 14 Mar 2023.