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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 : Recruiting
First Posted : March 21, 2018
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
Achillion Pharmaceuticals

Study Description
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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
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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
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Eculizumab

Arms and Interventions
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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
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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
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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
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
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Information from the National Library of Medicine

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


Contacts
Contact: Clinical Operations +1 203-752-5577 PNHTrialInquiries@achillion.com

Locations
United States, Maryland
John Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Donna Dorr    410-502-2547    dorrdo@jhmi.edu   
Principal Investigator: Robert Brodsky, M.D.         
United States, Ohio
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Sarah Kaufman    216-445-1019    kaufmas3@ccf.org   
Contact: Jaroslaw Maciejewski, M.D., Ph.D.    +1-216-445-5962    maciejj@ccf.org   
Principal Investigator: Jaroslaw Maciejewski, M.D., Ph.D.         
Sponsors and Collaborators
Achillion Pharmaceuticals
More Information
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Responsible Party: Achillion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03472885     History of Changes
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: June 20, 2018
Last Verified: June 2018

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

Keywords provided by Achillion 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