Paroxysmal Nocturnal Hemoglobinuria (PNH)Phase 2NCT03053102
Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
A Phase 2 study testing Danicopan in people with Paroxysmal Nocturnal Hemoglobinuria (PNH), run by Alexion Pharmaceuticals, Inc. at 5 sites in 4 countries.
Trial summary
The purpose of this study was to determine the safety and efficacy of ACH-0144471 (also known as danicopan and ALXN2040) in currently untreated 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?
- Danicopan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 31 Mar 2017to 14 Nov 2018
- 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
- Currently untreated PNH participants with PNH Type III erythrocyte and/or granulocyte clone size ≥10% and anemia (hemoglobin <12 grams/deciliter) with adequate reticulocytosis (as determined by the Investigator).
- LDH ≥1.5 x the upper limit of normal.
- Platelets ≥50,000/microliter without the need for platelet transfusions.
- Documentation of vaccination for Neisseria meningitidis, Haemophilus influenza, and Streptococcus pneumoniae, or willingness to receive vaccinations during the screening period.
- Negative pregnancy test for females prior to dosing and throughout the study.
Who cannot join
- History of a major organ transplant (for example, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
- Participants who had received another investigational agent within 30 days or 5 half-lives of the investigational agent prior to study entry, whichever is greater.
- Participants who had received eculizumab at any dose or interval within the past 75 days before study entry.
- Participants with known or suspected complement deficiency.
- Participants with active bacterial infection or clinically significant active viral infection, a body temperature >38°Celsius, or other evidence of infection on Day 1, or with a history of febrile illness within 14 days prior to first study drug administration.
- History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection.
- Females who were 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 was pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration.
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
About this study
Official title: A Phase 2 Open-Label Proof of Concept Study to Assess the Efficacy, Safety, and Pharmacokinetics of ACH-0144471 in Untreated Patients With Paroxysmal Nocturnal Hemoglobinuria
The purpose of this study was to determine the safety and efficacy of ACH-0144471 (also known as danicopan and ALXN2040) in currently untreated participants with PNH.
Read the detailed description
After 12 weeks of treatment, participants deriving clinical benefit were offered enrollment in a separate long-term extension study (ACH471-103, NCT03181633).
- Being tested
- Danicopan
- Keywords
- PNH, Paroxysmal, Hemoglobinuria
- 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.
DanicopanDrug
Also called ACH-0144471, ACH-4471, ACH4471, 4471
Danicopan was administered as multiple oral doses over a period of at least 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Danicopan | Experimental | Starting doses of danicopan ranged from 100 to 150 milligrams (mg) three times daily (TID), with subsequent dose escalation up to 200 mg TID based on response (clinical and biochemical) for 28 days (Part 1). Participants with reductions in lactate dehydrogenase (LDH) meeting specified criteria were offered continued dosing beyond Day 28, for up to 8 additional weeks (Part 2). Receives: Drug: Danicopan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline In Serum LDH Levels At Day 28
Change from Baseline = Serum LDH levels on Day 28 - Baseline Serum LDH levels.
Measured: Baseline, Day 28
Secondary outcomes (10)
Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84
Change from Baseline = Hgb levels on Days 28 or 84 - Baseline Hgb levels.
Measured: Baseline, Days 28 and 84
Change From Baseline In Serum LDH Levels At Day 84
Change from Baseline = Serum LDH levels on Day 84 - Baseline Serum LDH levels.
Measured: Baseline, Day 84
Paroxysmal Nocturnal Hemoglobinuria (PNH) Type III Red Blood Cell (RBC) Clone Size
PNH RBC, summed type III, clone size levels were assessed from Baseline to Day 28 and Day 84. The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population.
Measured: Baseline, Day 28, and Day 84
Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (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 SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Measured: After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104)
Grade 3 And Grade 4 Laboratory Abnormalities
Laboratory abnormalities were determined from laboratory measurements analyzed at the central or local laboratories, and were graded using CTCAE.
Measured: After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Post-dose (AUC0-8)
Serial blood samples were collected predose and up to 8 hours postdose.
Measured: Days 6 and 20
PK: Maximum Plasma Concentration (Cmax)
Serial blood samples were collected predose and up to 12 hours postdose.
Measured: Days 6 and 20
PK: Time To Maximum Concentration (Tmax)
Serial blood samples were collected predose and up to 12 hours postdose.
Measured: Days 6 and 20
Complement Alternative Pathway (AP) Functional Activity
Serum AP functional activity was measured by the Wieslab functional immunoassay method.
Measured: Baseline and Day 28
Complement Bb
Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA).
Measured: Baseline and Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2017
- Study start31 Mar 2017
- Primary completion14 Nov 2018
- Study completion14 Nov 2018
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 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
- NCT03053102
- Sponsor's protocol ID
- ACH471-100
- Other IDs
- 2016-002652-25, U1111-1190-3490, 2016
- Status last verified
- May 2022
- First submitted
- 1 Feb 2017
- Last updated
- 23 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Risitano AM, Kulasekararaj AG, Lee JW, Maciejewski JP, Notaro R, Brodsky R, Huang M, Geffner M, Browett P. Danicopan: an oral complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria. Haematologica. 2021 Dec 1;106(12):3188-3197. doi: 10.3324/haematol.2020.261826.
PubMed 33121236
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open-Label Proof of Concept Study to Assess the Efficacy, Safety, and Pharmacokinetics of ACH-0144471 in Untreated Patients With Paroxysmal Nocturnal Hemoglobinuria
- ClinicalTrials.gov ID
- NCT03053102
- Acronym / sponsor ID
- ACH471-100
- Keywords
- PNH, Paroxysmal, Hemoglobinuria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Achillion, a wholly owned subsidiary of Alexion
- Study start
- 31 Mar 2017 (actual)
- Primary completion
- 14 Nov 2018 (actual)
- Study completion
- 14 Nov 2018 (actual)
- First posted
- 14 Feb 2017 (actual)
- Results
- Posted 2 Jun 2021
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 was to determine the safety and efficacy of ACH-0144471 (also known as danicopan and ALXN2040) in currently untreated participants with PNH.
Detailed description
After 12 weeks of treatment, participants deriving clinical benefit were offered enrollment in a separate long-term extension study (ACH471-103, NCT03181633).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Danicopan | Experimental | Drug: DanicopanStarting doses of danicopan ranged from 100 to 150 milligrams (mg) three times daily (TID), with subsequent dose escalation up to 200 mg TID based on response (clinical and biochemical) for 28 days (Part 1). Participants with reductions in lactate dehydrogenase (LDH) meeting specified criteria were offered continued dosing beyond Day 28, for up to 8 additional weeks (Part 2). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Currently untreated PNH participants with PNH Type III erythrocyte and/or granulocyte clone size ≥10% and anemia (hemoglobin <12 grams/deciliter) with adequate reticulocytosis (as determined by the Investigator).
- LDH ≥1.5 x the upper limit of normal.
- Platelets ≥50,000/microliter without the need for platelet transfusions.
- Documentation of vaccination for Neisseria meningitidis, Haemophilus influenza, and Streptococcus pneumoniae, or willingness to receive vaccinations during the screening period.
- Negative pregnancy test for females prior to dosing and throughout the study.
Key exclusion criteria (7 listed)
- History of a major organ transplant (for example, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
- Participants who had received another investigational agent within 30 days or 5 half-lives of the investigational agent prior to study entry, whichever is greater.
- Participants who had received eculizumab at any dose or interval within the past 75 days before study entry.
- Participants with known or suspected complement deficiency.
- Participants with active bacterial infection or clinically significant active viral infection, a body temperature >38°Celsius, or other evidence of infection on Day 1, or with a history of febrile illness within 14 days prior to first 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 |
|---|---|---|
| DanicopanAlso: ACH-0144471, ACH-4471, ACH4471, 4471Danicopan was administered as multiple oral doses over a period of at least 28 days. | Drug | Danicopan |
Primary outcome
Change From Baseline In Serum LDH Levels At Day 28
Time frame: Baseline, Day 28
Change from Baseline = Serum LDH levels on Day 28 - Baseline Serum LDH levels.
10 secondary outcomes
Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84
Time frame: Baseline, Days 28 and 84
Change From Baseline In Serum LDH Levels At Day 84
Time frame: Baseline, Day 84
Paroxysmal Nocturnal Hemoglobinuria (PNH) Type III Red Blood Cell (RBC) Clone Size
Time frame: Baseline, Day 28, and Day 84
Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation
Time frame: After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104)
Grade 3 And Grade 4 Laboratory Abnormalities
Time frame: After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Post-dose (AUC0-8)
Time frame: Days 6 and 20
PK: Maximum Plasma Concentration (Cmax)
Time frame: Days 6 and 20
PK: Time To Maximum Concentration (Tmax)
Time frame: Days 6 and 20
Complement Alternative Pathway (AP) Functional Activity
Time frame: Baseline and Day 28
Complement Bb
Time frame: Baseline and Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33121236Risitano AM, Kulasekararaj AG, Lee JW, Maciejewski JP, Notaro R, Brodsky R, Huang M, Geffner M, Browett P. Danicopan: an oral complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria. Haematologica. 2021 Dec 1;106(12):3188-3197. doi: 10.3324/haematol.2020.261826.
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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 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Danicopan in people with Paroxysmal Nocturnal Hemoglobinuria (PNH), run by Alexion Pharmaceuticals, Inc. at 5 sites in 4 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 23 Jun 2022. 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 Italy, New Zealand, South Korea, 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 2 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 Serum LDH Levels At Day 28 (time frame: Baseline, Day 28). 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 NCT03053102, 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 23 Jun 2022.