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

NCT03181633 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: ACH471-1032017-000665-79U1111-1196-0653
• Study Type: interventional
• Target: 8
• Locations: 3 countries
• Sites: 4

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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

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

Outcome Measures

Primary Outcomes (9)

• 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.

  Baseline, Week 25

• 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.

  Baseline, Week 25

• 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.

  Baseline, Week 25

• 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

  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.

  Baseline, Week 25

• 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.

  Baseline, Week 25

• 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.

  Baseline, Week 25

• 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.

  Baseline up to 4.5 years

Secondary Outcomes (8)

• Change From Baseline in LDH Level at Weeks 49 and 169

  Baseline, Weeks 49 and 169

• 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 in Reticulocyte Counts at Weeks 49 and 169

  Baseline, Weeks 49 and 169

• Change From Baseline in PNH Clone Size at Weeks 49 and 73

  Baseline, Weeks 49 and 73

• Change From Baseline in AP Complement Functional Activity at Weeks 49 and 145

  Baseline, Weeks 49 and 145

Study Arms (1)

ACH-0144471

EXPERIMENTAL

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

Drug: ACH-0144471

Interventions

ACH-0144471 DRUG

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

ACH-0144471

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead
• Achillion, a wholly owned subsidiary of Alexion: collaborator

Study Sites (4)

Clinical Trial Site

Avellino, Italy

Location

Clinical Trial Site

Naples, Italy

Location

Clinical Trial Site

Auckland, New Zealand

Location

Clinical Trial Site

Seoul, South Korea

Location

Related Publications (1)

• Kulasekararaj AG, Browett PJ, Risitano AM, Patriquin CJ, Yenerel MN, Marceau D, Sahin F, Algarra L, Ogawa M, Yu J, Cross N, Notaro R, Lee JW, Brodsky RA. Efficacy and Safety of Vemircopan as Monotherapy in Patients With Paroxysmal Nocturnal Hemoglobinuria. Blood Adv. 2025 Oct 22:bloodadvances.2025017731. doi: 10.1182/bloodadvances.2025017731. Online ahead of print.

  PMID: 41124654 DERIVED

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal; Hemoglobinuria

Interventions

danicopan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Alexion Pharmaceuticals, Inc.
• Organization: Alexion Pharmaceuticals, Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2017
• First Posted: June 9, 2017
• Study Start: June 22, 2017
• Primary Completion: January 4, 2022
• Study Completion: January 4, 2022
• Last Updated: March 14, 2023
• Results First Posted: March 14, 2023

Record last verified: 2023-02

Locations

IT (2); NZ (1); KR (1)