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A Long-Term Treatment Study of ACH-0144471 in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ACH-0144471
Sponsored by
Alexion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria focused on measuring PNH, Paroxysmal, Hemoglobinuria, ACH-0144471, ALXN2040, Danicopan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Study designed to include up to 12 participants who completed treatment in Study ACH471-100 and demonstrated clinical benefit from ACH-0144471 with no significant safety or tolerability concerns.
  • Negative pregnancy test for females prior to dosing and throughout the study.

Exclusion Criteria:

  • Have developed any clinically relevant co-morbidities while participating in Study ACH471-100 that would make the participant inappropriate for the continuation of treatment with ACH-0144471, in the opinion of the Investigator.
  • Have developed any clinically significant laboratory abnormalities while participating in Study ACH471-100 that, in the opinion of the Investigator, would make the participant inappropriate for the study or put the participant at undue risk.
  • Females who are 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 is pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration.

Sites / Locations

  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ACH-0144471

Arm Description

All participants will receive ACH-0144471 during the treatment period.

Outcomes

Primary Outcome Measures

Change From Baseline in LDH Level at Week 25
Change from Baseline = Serum LDH levels at Week 25 - Baseline Serum LDH levels. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in Hgb Level in the Absence of RBC Transfusion at Week 25
Change from Baseline = Hgb levels at Week 25 - Baseline Hgb levels. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in Reticulocyte Counts at Week 25
Change from Baseline = reticulocyte count at Week 25 - Baseline reticulocyte count. Baseline was the baseline value from the primary Study ACH471-100.
Number of RBC Units Transfused
Number of RBC Transfusion Instances
Change From Baseline in PNH Clone Size at Week 25
The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Change from Baseline = PNH clone size at Week 25 - Baseline PNH clone size. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in AP Complement Functional Activity at Week 25
Serum AP functional activity was measured by the Wieslab functional immunoassay method. Change from Baseline = Serum AP functional activity at Week 25 - Baseline Serum AP functional activity. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in Free Hgb at Week 25
Change from Baseline = free Hgb at Week 25 - Baseline free Hgb. Baseline was the baseline value from the primary Study ACH471-100.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Grade 3 and Grade 4 Adverse Events (AEs), And 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 all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Secondary Outcome Measures

Change From Baseline in LDH Level at Weeks 49 and 169
Change from Baseline = Serum LDH levels at specified postbaseline visit - Baseline Serum LDH levels. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in Hgb Level in the Absence of RBC Transfusion at Weeks 49 and 169
Change from Baseline = Hgb levels at specified postbaseline visit - Baseline Hgb levels. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in Reticulocyte Counts at Weeks 49 and 169
Change from Baseline = reticulocyte count at specified postbaseline visit - Baseline reticulocyte count. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in PNH Clone Size at Weeks 49 and 73
The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Change from Baseline = PNH clone size at specified postbaseline visit - Baseline PNH clone size. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in AP Complement Functional Activity at Weeks 49 and 145
Serum AP functional activity was measured by the Wieslab functional immunoassay method. Change from Baseline = Serum AP functional activity at specified postbaseline visit - Baseline Serum AP functional activity. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in Free Hgb at Weeks 49 and 169
Change from Baseline = free Hgb at specified postbaseline visit - Baseline free Hgb. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at Weeks 21, 41, and 153
The FACIT-Fatigue scale is a collection of quality of life questionnaires pertaining to the management of fatigue symptoms due to a chronic illness. The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days. Participants score each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores range from 0 to 52, with higher score indicating better quality of life.
Change From Baseline in European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 Scale (EORTC-QLQ-C30): Global Health Status/Qol Score at Weeks 21, 41, and 153
EORTC-QLQ-C30 is comprised of 30 questions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & other single items. For each item, high score = high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health (global health status) and quality of life, coded on 7-point scale (1=very poor to 7=excellent). Answers were converted into grading scale, with total score between 0 and 100. A high score represented a favourable outcome with a best quality of life for participant.

Full Information

First Posted
June 5, 2017
Last Updated
February 14, 2023
Sponsor
Alexion
Collaborators
Achillion, a wholly owned subsidiary of Alexion
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1. Study Identification

Unique Protocol Identification Number
NCT03181633
Brief Title
A Long-Term Treatment Study of ACH-0144471 in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Official Title
An Open-Label Study to Evaluate Efficacy and Safety of Long-Term Treatment With ACH-0144471 in Participants Who Completed Clinical Study ACH471-100
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
June 22, 2017 (Actual)
Primary Completion Date
January 4, 2022 (Actual)
Study Completion Date
January 4, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion
Collaborators
Achillion, a wholly owned subsidiary of Alexion

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the long-term safety and efficacy of ACH-0144471 in participants with paroxysmal nocturnal hemoglobinuria (PNH) who have demonstrated clinical benefit from ACH-0144471 in Study ACH471-100. This study is designed to include up to 12 participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria
Keywords
PNH, Paroxysmal, Hemoglobinuria, ACH-0144471, ALXN2040, Danicopan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ACH-0144471
Arm Type
Experimental
Arm Description
All participants will receive ACH-0144471 during the treatment period.
Intervention Type
Drug
Intervention Name(s)
ACH-0144471
Intervention Description
ACH-0144471 will be administered to all participants enrolled in the study.
Primary Outcome Measure Information:
Title
Change From Baseline in LDH Level at Week 25
Description
Change from Baseline = Serum LDH levels at Week 25 - Baseline Serum LDH levels. Baseline was the baseline value from the primary Study ACH471-100.
Time Frame
Baseline, Week 25
Title
Change From Baseline in Hgb Level in the Absence of RBC Transfusion at Week 25
Description
Change from Baseline = Hgb levels at Week 25 - Baseline Hgb levels. Baseline was the baseline value from the primary Study ACH471-100.
Time Frame
Baseline, Week 25
Title
Change From Baseline in Reticulocyte Counts at Week 25
Description
Change from Baseline = reticulocyte count at Week 25 - Baseline reticulocyte count. Baseline was the baseline value from the primary Study ACH471-100.
Time Frame
Baseline, Week 25
Title
Number of RBC Units Transfused
Time Frame
Baseline up to Week 169
Title
Number of RBC Transfusion Instances
Time Frame
Baseline up to Week 169
Title
Change From Baseline in PNH Clone Size at Week 25
Description
The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Change from Baseline = PNH clone size at Week 25 - Baseline PNH clone size. Baseline was the baseline value from the primary Study ACH471-100.
Time Frame
Baseline, Week 25
Title
Change From Baseline in AP Complement Functional Activity at Week 25
Description
Serum AP functional activity was measured by the Wieslab functional immunoassay method. Change from Baseline = Serum AP functional activity at Week 25 - Baseline Serum AP functional activity. Baseline was the baseline value from the primary Study ACH471-100.
Time Frame
Baseline, Week 25
Title
Change From Baseline in Free Hgb at Week 25
Description
Change from Baseline = free Hgb at Week 25 - Baseline free Hgb. Baseline was the baseline value from the primary Study ACH471-100.
Time Frame
Baseline, Week 25
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Grade 3 and Grade 4 Adverse Events (AEs), And AEs Leading To Discontinuation
Description
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 all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time Frame
Baseline up to 4.5 years
Secondary Outcome Measure Information:
Title
Change From Baseline in LDH Level at Weeks 49 and 169
Description
Change from Baseline = Serum LDH levels at specified postbaseline visit - Baseline Serum LDH levels. Baseline was the baseline value from the primary Study ACH471-100.
Time Frame
Baseline, Weeks 49 and 169
Title
Change From Baseline in Hgb Level in the Absence of RBC Transfusion at Weeks 49 and 169
Description
Change from Baseline = Hgb levels at specified postbaseline visit - Baseline Hgb levels. Baseline was the baseline value from the primary Study ACH471-100.
Time Frame
Baseline, Weeks 49 and 169
Title
Change From Baseline in Reticulocyte Counts at Weeks 49 and 169
Description
Change from Baseline = reticulocyte count at specified postbaseline visit - Baseline reticulocyte count. Baseline was the baseline value from the primary Study ACH471-100.
Time Frame
Baseline, Weeks 49 and 169
Title
Change From Baseline in PNH Clone Size at Weeks 49 and 73
Description
The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Change from Baseline = PNH clone size at specified postbaseline visit - Baseline PNH clone size. Baseline was the baseline value from the primary Study ACH471-100.
Time Frame
Baseline, Weeks 49 and 73
Title
Change From Baseline in AP Complement Functional Activity at Weeks 49 and 145
Description
Serum AP functional activity was measured by the Wieslab functional immunoassay method. Change from Baseline = Serum AP functional activity at specified postbaseline visit - Baseline Serum AP functional activity. Baseline was the baseline value from the primary Study ACH471-100.
Time Frame
Baseline, Weeks 49 and 145
Title
Change From Baseline in Free Hgb at Weeks 49 and 169
Description
Change from Baseline = free Hgb at specified postbaseline visit - Baseline free Hgb. Baseline was the baseline value from the primary Study ACH471-100.
Time Frame
Baseline, Weeks 49 and 169
Title
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at Weeks 21, 41, and 153
Description
The FACIT-Fatigue scale is a collection of quality of life questionnaires pertaining to the management of fatigue symptoms due to a chronic illness. The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days. Participants score each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores range from 0 to 52, with higher score indicating better quality of life.
Time Frame
Baseline, Weeks 21, 41, and 153
Title
Change From Baseline in European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 Scale (EORTC-QLQ-C30): Global Health Status/Qol Score at Weeks 21, 41, and 153
Description
EORTC-QLQ-C30 is comprised of 30 questions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & other single items. For each item, high score = high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health (global health status) and quality of life, coded on 7-point scale (1=very poor to 7=excellent). Answers were converted into grading scale, with total score between 0 and 100. A high score represented a favourable outcome with a best quality of life for participant.
Time Frame
Baseline, Weeks 21, 41, and 153

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Study designed to include up to 12 participants who completed treatment in Study ACH471-100 and demonstrated clinical benefit from ACH-0144471 with no significant safety or tolerability concerns. Negative pregnancy test for females prior to dosing and throughout the study. Exclusion Criteria: Have developed any clinically relevant co-morbidities while participating in Study ACH471-100 that would make the participant inappropriate for the continuation of treatment with ACH-0144471, in the opinion of the Investigator. Have developed any clinically significant laboratory abnormalities while participating in Study ACH471-100 that, in the opinion of the Investigator, would make the participant inappropriate for the study or put the participant at undue risk. Females who are 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 is pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration.
Facility Information:
Facility Name
Clinical Trial Site
City
Avellino
Country
Italy
Facility Name
Clinical Trial Site
City
Naples
Country
Italy
Facility Name
Clinical Trial Site
City
Seoul
Country
Korea, Republic of
Facility Name
Clinical Trial Site
City
Auckland
Country
New Zealand

12. IPD Sharing Statement

Learn more about this trial

A Long-Term Treatment Study of ACH-0144471 in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)

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