Paroxysmal Nocturnal Hemoglobinuria (PNH)Phase 2PNHNCT03472885
Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Response to Eculizumab
A Phase 2 study testing Danicopan and Eculizumab in people with Paroxysmal Nocturnal Hemoglobinuria (PNH), run by Alexion Pharmaceuticals, Inc. at 5 sites in 3 countries.
Trial summary
To determine the effectiveness of ACH-0144471 (also known as danicopan and ALXN2040) in improving anemia when given with eculizumab for 24 weeks in participants with PNH. Danicopan dose may be increased within each participant, to a maximum of 200 milligrams (mg) three times daily (TID) based on safety and efficacy at… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
- What is being tested?
- Danicopan and Eculizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 8 May 2018to 5 Jan 2023
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with PNH
- Have received at least one red blood cell transfusion within last 12 weeks
- Anemia with adequate reticulocytosis
- Must be on a stable regimen of eculizumab
- Platelet count ≥ 40,000/microliter without the need for platelet transfusions
- Documentation of vaccination for Neisseria meningitidis, Haemophilus influenza, and Streptococcus pneumoniae or willingness to receive vaccinations based on local guidelines
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- Willingness to receive antibiotic prophylaxis
- Female participants must use highly effective birth control to prevent pregnancy during the clinical trial and for 30 days after their last dose of study drug
- Male participants must use a highly effective birth control with a female partner to prevent pregnancy during the clinical trial and for 90 days after the last dose of study drug
Who cannot join
- Current evidence of bone marrow failure or aplastic anemia requiring treatment
- History of a major organ transplant or hematopoietic stem cell/marrow transplant
- Received another investigational agent within 30 days or 5 half-lives of the investigational agent prior to study entry, whichever is greater
- Documented C5 complement protein mutations
- Known or suspected complement deficiency
- Contraindication to any of the required vaccinations
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- Active bacterial infection or clinically significant active viral infection, a body temperature >38°C, or other evidence of infection
- History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection
- History of hypersensitivity reactions to commonly used antibacterial agents
- Note: Additional inclusion/exclusion criteria may apply, per protocol.
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
United States2 sites
Clinical Study Site
Baltimore, Maryland, 21287
Clinical Study Site
Cleveland, Ohio, 44195
About this study
Official title: A Phase 2 Open-label Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have an Inadequate Response to Eculizumab Monotherapy
To determine the effectiveness of ACH-0144471 (also known as danicopan and ALXN2040) in improving anemia when given with eculizumab for 24 weeks in participants with PNH. Danicopan dose may be increased within each participant, to a maximum of 200 milligrams (mg) three times daily (TID) based on safety and efficacy at protocol-specified time points.
Read the detailed description
The purpose of this study is to determine the effectiveness of danicopan in improving anemia, as measured by increased blood hemoglobin, when given with eculizumab (a drug commonly used for treatment of PNH) for 24 weeks in participants with PNH.
The 24-week treatment period was followed by a long-term extension phase. In the extension phase, participants received the same danicopan dose plus eculizumab as they were receiving at the end of 24-week treatment phase.
Results are reported for the 24-week treatment period.
- Being tested
- Danicopan, Eculizumab
- Keywords
- PNH, Paroxysmal Nocturnal Hemoglobinuria, ACH-0144471, Danicopan, Eculizumab, ALXN2040
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DanicopanDrug
Participants received a daily oral dose of danicopan TID during the treatment period.
EculizumabDrug
Also called Soliris
Participants received intravenous eculizumab administered at the participant's usual dose and schedule.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: 100 mg Danicopan TID + Eculizumab | Experimental | Starting dose of 100 mg danicopan TID in combination with eculizumab. Receives: Drug: Danicopan; Drug: Eculizumab |
| Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab | Experimental | Starting dose of 100 or 150 mg danicopan TID in combination with eculizumab. Receives: Drug: Danicopan; Drug: Eculizumab |
| Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab | Experimental | Starting dose of 100, 150, or 200 mg danicopan TID in combination with eculizumab. Receives: Drug: Danicopan; Drug: Eculizumab |
| Group 4: Optimal Dose of Danicopan TID + Eculizumab | Experimental | Optimal dose (starting dose of either 100, 150, or 200 mg, as determined from Groups 1-3) of danicopan TID in combination with eculizumab. Receives: Drug: Danicopan; Drug: Eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline In Hemoglobin At Week 24
Measured: Baseline, Week 24
Secondary outcomes (4)
Number Of Units Of Red Blood Cells (RBCs) Transfused During 24 Weeks Of Treatment
Measured: Within 24 weeks prior to first dose and during 24-week treatment period
Number Of Participants Without RBC Transfusions During 24 Weeks Of Treatment
Measured: Within 24 weeks prior to first dose and during 24-week treatment period
Change From Baseline In Lactate Dehydrogenase At Week 24
Measured: Baseline, Week 24
Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Adverse Events (AEs), And Events Leading To Discontinuation Of Study Drug
An AE was defined 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 SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Measured: Day 1 (after dosing) through end of study (maximum exposure: 1631 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2018
- Study start8 May 2018
- Primary completion20 Sep 2019
- Study completion5 Jan 2023
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.
- 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
- Model description
- Four groups will be studied and enrolled sequentially.
- Masking
- None (open label)
- Enrolment
- 12 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
- NCT03472885
- Sponsor's protocol ID
- ACH471-101
- Other IDs
- 2016-003526-16, U1111-1209-4655, 2016
- Acronym
- PNH
- Status last verified
- Nov 2023
- First submitted
- 15 Mar 2018
- Last updated
- 12 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kulasekararaj AG, Risitano AM, Maciejewski JP, Notaro R, Browett P, Lee JW, Huang M, Geffner M, Brodsky RA. Phase 2 study of danicopan in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab. Blood. 2021 Nov 18;138(20):1928-1938. doi: 10.1182/blood.2021011388.
PubMed 34314483
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open-label Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have an Inadequate Response to Eculizumab Monotherapy
- ClinicalTrials.gov ID
- NCT03472885
- Acronym / sponsor ID
- PNH / ACH471-101
- Keywords
- PNH, Paroxysmal Nocturnal Hemoglobinuria, ACH-0144471, Danicopan, Eculizumab, ALXN2040
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Achillion, a wholly owned subsidiary of Alexion
- Study start
- 8 May 2018 (actual)
- Primary completion
- 20 Sep 2019 (actual)
- Study completion
- 5 Jan 2023 (actual)
- First posted
- 21 Mar 2018 (actual)
- Results
- Posted 25 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the effectiveness of ACH-0144471 (also known as danicopan and ALXN2040) in improving anemia when given with eculizumab for 24 weeks in participants with PNH. Danicopan dose may be increased within each participant, to a maximum of 200 milligrams (mg) three times daily (TID) based on safety and efficacy at protocol-specified time points.
Detailed description
The purpose of this study is to determine the effectiveness of danicopan in improving anemia, as measured by increased blood hemoglobin, when given with eculizumab (a drug commonly used for treatment of PNH) for 24 weeks in participants with PNH.
The 24-week treatment period was followed by a long-term extension phase. In the extension phase, participants received the same danicopan dose plus eculizumab as they were receiving at the end of 24-week treatment phase.
Results are reported for the 24-week treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Four groups will be studied and enrolled sequentially.
| Arm | Type | Receives |
|---|---|---|
| Group 1: 100 mg Danicopan TID + Eculizumab | Experimental | Drug: Danicopan, Drug: EculizumabStarting dose of 100 mg danicopan TID in combination with eculizumab. |
| Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab | Experimental | Drug: Danicopan, Drug: EculizumabStarting dose of 100 or 150 mg danicopan TID in combination with eculizumab. |
| Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab | Experimental | Drug: Danicopan, Drug: EculizumabStarting dose of 100, 150, or 200 mg danicopan TID in combination with eculizumab. |
| Group 4: Optimal Dose of Danicopan TID + Eculizumab | Experimental | Drug: Danicopan, Drug: EculizumabOptimal dose (starting dose of either 100, 150, or 200 mg, as determined from Groups 1-3) of danicopan TID in combination with eculizumab. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Diagnosed with PNH
- Have received at least one red blood cell transfusion within last 12 weeks
- Anemia with adequate reticulocytosis
- Must be on a stable regimen of eculizumab
- Platelet count ≥ 40,000/microliter without the need for platelet transfusions
Key exclusion criteria (10 listed)
- Current evidence of bone marrow failure or aplastic anemia requiring treatment
- History of a major organ transplant or hematopoietic stem cell/marrow transplant
- Received another investigational agent within 30 days or 5 half-lives of the investigational agent prior to study entry, whichever is greater
- Documented C5 complement protein mutations
- Known or suspected complement deficiency
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 |
|---|---|---|
| DanicopanParticipants received a daily oral dose of danicopan TID during the treatment period. | Drug | Group 1: 100 mg Danicopan TID + Eculizumab, Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab, Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab, Group 4: Optimal Dose of Danicopan TID + Eculizumab |
| EculizumabAlso: SolirisParticipants received intravenous eculizumab administered at the participant's usual dose and schedule. | Drug | Group 1: 100 mg Danicopan TID + Eculizumab, Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab, Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab, Group 4: Optimal Dose of Danicopan TID + Eculizumab |
Primary outcome
Change From Baseline In Hemoglobin At Week 24
Time frame: Baseline, Week 24
4 secondary outcomes
Number Of Units Of Red Blood Cells (RBCs) Transfused During 24 Weeks Of Treatment
Time frame: Within 24 weeks prior to first dose and during 24-week treatment period
Number Of Participants Without RBC Transfusions During 24 Weeks Of Treatment
Time frame: Within 24 weeks prior to first dose and during 24-week treatment period
Change From Baseline In Lactate Dehydrogenase At Week 24
Time frame: Baseline, Week 24
Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Adverse Events (AEs), And Events Leading To Discontinuation Of Study Drug
Time frame: Day 1 (after dosing) through end of study (maximum exposure: 1631 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34314483Kulasekararaj AG, Risitano AM, Maciejewski JP, Notaro R, Browett P, Lee JW, Huang M, Geffner M, Brodsky RA. Phase 2 study of danicopan in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab. Blood. 2021 Nov 18;138(20):1928-1938. doi: 10.1182/blood.2021011388.
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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.
5 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 Danicopan and Eculizumab in people with Paroxysmal Nocturnal Hemoglobinuria (PNH), run by Alexion Pharmaceuticals, Inc. at 5 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 9 inclusion and 10 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 12 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Italy, United Kingdom. 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 25 Jun 2021). 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 Hemoglobin At Week 24 (time frame: Baseline, Week 24). 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 NCT03472885, 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 12 Dec 2023.