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

Phase 2

Completed

Conditions: Paroxysmal Nocturnal Hemoglobinuria

Interventions: Drug: ACH-0144471

Registration Number: NCT03181633

Lead Sponsor: Alexion Pharmaceuticals, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 8

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Hgb Level in the Absence of RBC Transfusion at Week 25	Baseline, Week 25	Change from Baseline = Hgb levels at Week 25 - Baseline Hgb levels. Baseline was the baseline value from the primary Study ACH471-100.
Number of RBC Units Transfused	Baseline up to Week 169
Number of RBC Transfusion Instances	Baseline up to Week 169
Change From Baseline in PNH Clone Size at Week 25	Baseline, 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 Free Hgb at Week 25	Baseline, Week 25	Change from Baseline = free Hgb at Week 25 - Baseline free Hgb. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in LDH Level at Week 25	Baseline, 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 Reticulocyte Counts at Week 25	Baseline, Week 25	Change from Baseline = reticulocyte count at Week 25 - Baseline reticulocyte count. Baseline was the baseline value from the primary Study ACH471-100.
Change From Baseline in AP Complement Functional Activity at Week 25	Baseline, 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.
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	Baseline up to 4.5 years	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

Name	Time	Method
Change From Baseline in Reticulocyte Counts at Weeks 49 and 169	Baseline, 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	Baseline, 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	Baseline, 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 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	Baseline, 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.
Change From Baseline in LDH Level at Weeks 49 and 169	Baseline, 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 Free Hgb at Weeks 49 and 169	Baseline, 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 Hgb Level in the Absence of RBC Transfusion at Weeks 49 and 169	Baseline, 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 Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at Weeks 21, 41, and 153	Baseline, 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.