A Treatment Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) With Inadequate Response to Eculizumab (PNH)
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ClinicalTrials.gov Identifier: NCT03472885 |
Recruitment Status :
Active, not recruiting
First Posted : March 21, 2018
Last Update Posted : November 5, 2020
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Paroxysmal Nocturnal Hemoglobinuria (PNH) | Drug: ACH-0144471 Drug: Eculizumab | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 12 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Intervention Model Description: | Four groups will be studied and enrolled sequentially. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | May 8, 2018 |
Actual Primary Completion Date : | September 20, 2019 |
Estimated Study Completion Date : | December 31, 2020 |

Arm | Intervention/treatment |
---|---|
Experimental: Group 1: 100 mg ACH-0144471 TID + Eculizumab
100 mg ACH-0144471 TID to start in combination with eculizumab.
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Drug: ACH-0144471
All patients will receive a daily oral dose of ACH-0144471 TID during the treatment period. Drug: Eculizumab All patients will receive intravenous (IV) eculizumab administered at the patient's usual dose and schedule.
Other Name: Soliris |
Experimental: Group 2: 150 mg ACH-0144471 TID + Eculizumab
150 mg ACH-0144471 TID to start in combination with eculizumab.
|
Drug: ACH-0144471
All patients will receive a daily oral dose of ACH-0144471 TID during the treatment period. Drug: Eculizumab All patients will receive intravenous (IV) eculizumab administered at the patient's usual dose and schedule.
Other Name: Soliris |
Experimental: Group 3: 200 mg ACH-0144471 TID + Eculizumab
200 mg ACH-0144471 TID to start in combination with eculizumab.
|
Drug: ACH-0144471
All patients will receive a daily oral dose of ACH-0144471 TID during the treatment period. Drug: Eculizumab All patients will receive intravenous (IV) eculizumab administered at the patient's usual dose and schedule.
Other Name: Soliris |
Experimental: Group 4: Optimal Dose of ACH-0144471 TID + Eculizumab
Optimal dose (100 mg, 150 mg or 200 mg, as determined from Groups 1-3) of ACH-0144471 TID to start, in combination with eculizumab.
|
Drug: ACH-0144471
All patients will receive a daily oral dose of ACH-0144471 TID during the treatment period. Drug: Eculizumab All patients will receive intravenous (IV) eculizumab administered at the patient's usual dose and schedule.
Other Name: Soliris |
- Median Hemoglobin (Hgb) During the 24-Week Treatment Phase Compared to Baseline: Optimal Dose Group [ Time Frame: Baseline (Day 1), up to 24 weeks ]
- Median Hemoglobin (Hgb) During the 24-Week Treatment Phase Compared to Baseline: Non-Optimal Dose Groups [ Time Frame: Baseline (Day 1), up to 24 weeks ]Median Hgb over the time period that the participant received the highest dose level during the 24-week treatment phase compared to baseline.
- Number of Units of Red Blood Cells (RBCs) Transfused During 24 Weeks of Treatment [ Time Frame: up to 24 weeks ]
- Number of Participants Without RBC Transfusions During 24 Weeks of Treatment [ Time Frame: up to 24 weeks ]
- Percent of Participants Without RBC Transfusions During 24 Weeks of Treatment [ Time Frame: up to 24 weeks ]
- Change From Baseline in Lactate Dehydrogenase (LDH) During 24 Weeks of Treatment [ Time Frame: up to 24 weeks ]
- 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: up to 24 weeks ]

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Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Diagnosed with PNH
- 18 to 65 years of age
- Have received at least one RBC transfusion within last 12 weeks
- Anemia with adequate reticulocytosis
- Must be on a stable regimen of eculizumab
- Platelet count ≥ 40,000/μL without the need for platelet transfusions
- Documentation of vaccination for N. meningitidis, H. influenza, and S. pneumoniae or willingness to receive vaccinations based on local guidelines
- 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.
Key Exclusion Criteria:
- 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 mutations
- Known or suspected complement deficiency
- Contraindication to any of the required vaccinations
- 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03472885
United States, Maryland | |
John Hopkins | |
Baltimore, Maryland, United States, 21287 | |
United States, Ohio | |
Cleveland Clinic | |
Cleveland, Ohio, United States, 44195 |
Responsible Party: | Alexion Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT03472885 |
Other Study ID Numbers: |
ACH471-101 2016-003526-16 ( EudraCT Number ) U1111-1209-4655 ( Other Identifier: UTN ) |
First Posted: | March 21, 2018 Key Record Dates |
Last Update Posted: | November 5, 2020 |
Last Verified: | October 2020 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
PNH Paroxysmal Nocturnal Hemoglobinuria ACH-0144471 eculizumab |
Hemoglobinuria Hemoglobinuria, Paroxysmal Proteinuria Urination Disorders Urologic Diseases Urological Manifestations |
Anemia, Hemolytic Anemia Hematologic Diseases Myelodysplastic Syndromes Bone Marrow Diseases |