A Treatment Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) With Inadequate Response to Eculizumab (PNH)

• ClinicalTrials.gov Identifier: NCT03472885
• Recruitment Status: Active, not recruiting
• First Posted: March 21, 2018
• Last Update Posted: December 3, 2019
• Sponsor: Alexion Pharmaceuticals
• Information provided by (Responsible Party): Alexion Pharmaceuticals

Study Description

Brief Summary:

To determine the effectiveness of ACH-0144471 in improving anemia when given with eculizumab for 24 weeks in patients with PNH.

Condition or disease	Intervention/treatment	Phase
Paroxysmal Nocturnal Hemoglobinuria (PNH)	Drug: ACH-0144471; Drug: Eculizumab	Phase 2

Detailed Description:

The purpose of this study is to determine the effectiveness of ACH-0144471 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 patients with PNH.

Study Design

• 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

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1: 100 mg ACH-0144471 TID + Eculizumab; 100 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 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

Outcome Measures

Primary Outcome Measures :

1. Median Hemoglobin (Hgb) During the 24-Week Treatment Phase Compared to Baseline: Optimal Dose Group [ Time Frame: Baseline (Day 1), up to 24 weeks ]
2. 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.

Secondary Outcome Measures :

1. Number of Units of Red Blood Cells (RBCs) Transfused During 24 Weeks of Treatment [ Time Frame: up to 24 weeks ]
2. Number of Participants Without RBC Transfusions During 24 Weeks of Treatment [ Time Frame: up to 24 weeks ]
3. Percent of Participants Without RBC Transfusions During 24 Weeks of Treatment [ Time Frame: up to 24 weeks ]
4. Change From Baseline in Lactate Dehydrogenase (LDH) During 24 Weeks of Treatment [ Time Frame: up to 24 weeks ]
5. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Maryland

John Hopkins

Baltimore, Maryland, United States, 21287

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

Alexion Pharmaceuticals

More Information

• 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
• Last Update Posted: December 3, 2019
• Last Verified: December 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alexion Pharmaceuticals:

PNH; Paroxysmal Nocturnal Hemoglobinuria; ACH-0144471; eculizumab

Additional relevant MeSH terms:

Hemoglobinuria; Hemoglobinuria, Paroxysmal; Proteinuria; Urination Disorders; Urologic Diseases; Urological Manifestations; Signs and Symptoms; Anemia, Hemolytic; Anemia; Hematologic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases