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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-002652-25 | EudraCT Number | ||
| U1111-1190-3490 | Other Identifier | UTN |
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| Name | Class |
|---|---|
| Achillion, a wholly owned subsidiary of Alexion | INDUSTRY |
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The purpose of this study was to determine the safety and efficacy of ACH-0144471 (also known as danicopan and ALXN2040) in currently untreated participants with PNH.
After 12 weeks of treatment, participants deriving clinical benefit were offered enrollment in a separate long-term extension study (ACH471-103, NCT03181633).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Danicopan | Experimental | Starting doses of danicopan ranged from 100 to 150 milligrams (mg) three times daily (TID), with subsequent dose escalation up to 200 mg TID based on response (clinical and biochemical) for 28 days (Part 1). Participants with reductions in lactate dehydrogenase (LDH) meeting specified criteria were offered continued dosing beyond Day 28, for up to 8 additional weeks (Part 2). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Danicopan | Drug | Danicopan was administered as multiple oral doses over a period of at least 28 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline In Serum LDH Levels At Day 28 | Change from Baseline = Serum LDH levels on Day 28 - Baseline Serum LDH levels. | Baseline, Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84 | Change from Baseline = Hgb levels on Days 28 or 84 - Baseline Hgb levels. | Baseline, Days 28 and 84 |
| Change From Baseline In Serum LDH Levels At Day 84 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Florence | Italy | ||||
| Clinical Trial Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33121236 | Result | Risitano AM, Kulasekararaj AG, Lee JW, Maciejewski JP, Notaro R, Brodsky R, Huang M, Geffner M, Browett P. Danicopan: an oral complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria. Haematologica. 2021 Dec 1;106(12):3188-3197. doi: 10.3324/haematol.2020.261826. |
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The study was conducted in 2 parts. In Part 1, participants received danicopan for 28 days. Starting doses were 100 or 150 milligrams (mg) three times daily (TID). A further dose increase up to 175 mg TID (N=8 participants) and 200 mg TID (N=4 participants) was conducted. Participants with reductions in lactate dehydrogenase (LDH) meeting specified criteria were offered continued dosing beyond Day 28, for up to 8 additional weeks (Part 2).
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| ID | Title | Description |
|---|---|---|
| FG000 | Danicopan | Participants received danicopan 100 to 200 mg TID. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study Part 1: 28-Day Treatment |
| ||||||||||||||||
| Study Part 2: 84-Day Treatment |
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All participants who were enrolled in the study and received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Danicopan | Participants received danicopan 100 to 200 mg TID. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline In Serum LDH Levels At Day 28 | Change from Baseline = Serum LDH levels on Day 28 - Baseline Serum LDH levels. | All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified. | Posted | Mean | Standard Deviation | international units per liter (IU/L) | Baseline, Day 28 |
|
|
After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Danicopan | Participants received danicopan 100 to 200 mg TID. | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemolysis | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals Inc. | Alexion Pharmaceuticals Inc. | 855-752-2356 | clinicaltrials@alexion.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 13, 2018 | May 6, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 6, 2018 | May 7, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006457 | Hemoglobinuria, Paroxysmal |
| D006456 | Hemoglobinuria |
| ID | Term |
|---|---|
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000718467 | danicopan |
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Change from Baseline = Serum LDH levels on Day 84 - Baseline Serum LDH levels.
| Baseline, Day 84 |
| Paroxysmal Nocturnal Hemoglobinuria (PNH) Type III Red Blood Cell (RBC) Clone Size | PNH RBC, summed type III, clone size levels were assessed from Baseline to Day 28 and Day 84. The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. | Baseline, Day 28, and Day 84 |
| Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (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 SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104) |
| Grade 3 And Grade 4 Laboratory Abnormalities | Laboratory abnormalities were determined from laboratory measurements analyzed at the central or local laboratories, and were graded using CTCAE. | After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104). |
| Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Post-dose (AUC0-8) | Serial blood samples were collected predose and up to 8 hours postdose. | Days 6 and 20 |
| PK: Maximum Plasma Concentration (Cmax) | Serial blood samples were collected predose and up to 12 hours postdose. | Days 6 and 20 |
| PK: Time To Maximum Concentration (Tmax) | Serial blood samples were collected predose and up to 12 hours postdose. | Days 6 and 20 |
| Complement Alternative Pathway (AP) Functional Activity | Serum AP functional activity was measured by the Wieslab functional immunoassay method. | Baseline and Day 28 |
| Complement Bb | Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA). | Baseline and Day 28 |
| Naples |
| Italy |
| Clinical Trial Site | Auckland | New Zealand |
| Clinical Trial Site | Seoul | South Korea |
| Clinical Trial Site | London | United Kingdom |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84 | Change from Baseline = Hgb levels on Days 28 or 84 - Baseline Hgb levels. | All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified. | Posted | Mean | Standard Deviation | grams/deciliter (g/dL) | Baseline, Days 28 and 84 |
|
|
|
| Secondary | Change From Baseline In Serum LDH Levels At Day 84 | Change from Baseline = Serum LDH levels on Day 84 - Baseline Serum LDH levels. | All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified. | Posted | Mean | Standard Deviation | IU/L | Baseline, Day 84 |
|
|
|
| Secondary | Paroxysmal Nocturnal Hemoglobinuria (PNH) Type III Red Blood Cell (RBC) Clone Size | PNH RBC, summed type III, clone size levels were assessed from Baseline to Day 28 and Day 84. The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. | All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified. | Posted | Mean | Standard Deviation | percentage of the total cell population | Baseline, Day 28, and Day 84 |
|
|
|
| Secondary | Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (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 SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | All participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104) |
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|
|
| Secondary | Grade 3 And Grade 4 Laboratory Abnormalities | Laboratory abnormalities were determined from laboratory measurements analyzed at the central or local laboratories, and were graded using CTCAE. | All participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104). |
|
|
|
| Secondary | Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Post-dose (AUC0-8) | Serial blood samples were collected predose and up to 8 hours postdose. | All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified. PK analysis was not conducted on the 200 mg dose. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour (hr)*nanograms/milliliter (ng/mL) | Days 6 and 20 |
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|
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| Secondary | PK: Maximum Plasma Concentration (Cmax) | Serial blood samples were collected predose and up to 12 hours postdose. | All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified. PK analysis was not conducted on the 200 mg dose. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Days 6 and 20 |
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|
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| Secondary | PK: Time To Maximum Concentration (Tmax) | Serial blood samples were collected predose and up to 12 hours postdose. | All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified. PK analysis was not conducted on the 200 mg dose. | Posted | Median | Full Range | hr | Days 6 and 20 |
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| Secondary | Complement Alternative Pathway (AP) Functional Activity | Serum AP functional activity was measured by the Wieslab functional immunoassay method. | All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified. | Posted | Mean | Standard Deviation | percentage of activity | Baseline and Day 28 |
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| Secondary | Complement Bb | Plasma Bb was measured by enzyme-linked immunosorbent assay (ELISA). | All participants who received at least 1 dose of study drug and had analyzable data at the timepoints specified. | Posted | Mean | Standard Deviation | microgram (ug)/mL | Baseline and Day 28 |
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|
| 10 |
| 1 |
| 10 |
| 9 |
| 10 |
| Alanine aminotransferase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Irritability | Psychiatric disorders | MedDRA (18.1) | Systematic Assessment |
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| Iron deficiency | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Mouth ulceration | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Vaccination site erythema | General disorders | MedDRA (18.1) | Systematic Assessment |
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| Paroxysmal nocturnal haemoglobinuria | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (18.1) | Systematic Assessment |
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| Haemoglobinuria | Renal and urinary disorders | MedDRA (18.1) | Systematic Assessment |
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| Haemolysis | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
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| D009190 |
| Myelodysplastic Syndromes |
| D001855 | Bone Marrow Diseases |
| D011507 | Proteinuria |
| D014555 | Urination Disorders |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Part 1: Change from Baseline at Day 28 |
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| Part 2: Day 84 |
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| Part 2: Change from Baseline at Day 84 |
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| Change from Baseline |
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| Day 84 |
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| Title | Measurements |
|---|
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| AE leading to discontinuation |
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| Title | Measurements |
|---|---|
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| Low neutrophil count |
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| High triglycerides |
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| Day 20: 175 mg TID |
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| Day 20: 175 mg TID |
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| Day 20: 175 mg TID |
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