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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03472885
Recruitment Status : Active, not recruiting
First Posted : March 21, 2018
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Achillion Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE March 15, 2018
First Posted Date  ICMJE March 21, 2018
Last Update Posted Date August 20, 2019
Actual Study Start Date  ICMJE May 8, 2018
Estimated Primary Completion Date September 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 15, 2018)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03472885 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2018)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Treatment Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) With Inadequate Response to Eculizumab
Official Title  ICMJE A Phase 2 Open-label Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have an Inadequate Response to Eculizumab Monotherapy
Brief Summary To determine the effectiveness of ACH-0144471 in improving anemia when given with eculizumab for 24 weeks in patients with PNH.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Paroxysmal Nocturnal Hemoglobinuria (PNH)
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Group 1: 100 mg ACH-0144471 TID + Eculizumab
    100 mg ACH-0144471 TID to start in combination with eculizumab.
    Interventions:
    • Drug: ACH-0144471
    • Drug: Eculizumab
  • Experimental: Group 2: 150 mg ACH-0144471 TID + Eculizumab
    150 mg ACH-0144471 TID to start in combination with eculizumab.
    Interventions:
    • Drug: ACH-0144471
    • Drug: Eculizumab
  • Experimental: Group 3: 200 mg ACH-0144471 TID + Eculizumab
    200 mg ACH-0144471 TID to start in combination with eculizumab.
    Interventions:
    • Drug: ACH-0144471
    • Drug: Eculizumab
  • 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.
    Interventions:
    • Drug: ACH-0144471
    • Drug: Eculizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 15, 2018)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date September 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03472885
Other Study ID Numbers  ICMJE ACH471-101
2016-003526-16 ( EudraCT Number )
U1111-1209-4655 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Achillion Pharmaceuticals
Study Sponsor  ICMJE Achillion Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Achillion Pharmaceuticals
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP