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

Browse trials for

• Hemoglobinuria 107
• Hemoglobinuria, Paroxysmal 188

Keywords

• PNH
• Paroxysmal
• Hemoglobinuria
• ACH-0144471
• ALXN2040
• Danicopan

Study arms

• Experimental
  ACH-0144471

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

  Drug: ACH-0144471

Interventions

• DrugACH-0144471

  ACH-0144471 will be administered to all participants enrolled in the study.

Primary outcomes

1. 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.

   Time frame: Baseline, Week 25

2. 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.

   Time frame: Baseline, Week 25

3. 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.

   Time frame: Baseline, Week 25

4. Number of RBC Units Transfused

   Time frame: Baseline up to Week 169

5. Number of RBC Transfusion Instances

   Time frame: Baseline up to Week 169

6. 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.

   Time frame: Baseline, Week 25

7. 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.

   Time frame: Baseline, Week 25

8. 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.

   Time frame: Baseline, Week 25

9. 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.

   Time frame: Baseline up to 4.5 years

Secondary outcomes

1. 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.

   Time frame: Baseline, Weeks 49 and 169

2. 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.

   Time frame: Baseline, Weeks 49 and 169

3. 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.

   Time frame: Baseline, Weeks 49 and 169

4. 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.

   Time frame: Baseline, Weeks 49 and 73

5. 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.

   Time frame: Baseline, Weeks 49 and 145

6. 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.

   Time frame: Baseline, Weeks 49 and 169

7. 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.

   Time frame: Baseline, Weeks 21, 41, and 153

8. 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.

   Time frame: Baseline, Weeks 21, 41, and 153

Baseline characteristics

2 further baseline measures are reported on the registry.

Study documents

• Study protocol · Jun 4, 2021
• Statistical analysis plan · Feb 23, 2021

Documents are hosted by the registry — open the source record to download them.