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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-000663-33 | EudraCT Number |
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The primary purpose of this proof-of-concept clinical study was to evaluate the efficacy and safety of the study drug, ACH-0144471 (also known as danicopan and ALXN2040), in participants with C3G who also had significant proteinuria attributable to C3G.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Danicopan (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period) | Active Comparator | Danicopan was administered at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then dosage was to be increased to 200 mg TID for the remainder of the 6-month treatment period. All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID. |
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| Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period) | Placebo Comparator | Placebo was administered TID during the 6-month treatment period. All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Danicopan | Drug | Danicopan was administered as an oral tablet. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline In Composite Biopsy Score At Week 28 | The composite biopsy score was based on a score incorporating changes in the activity index, glomerular C3c staining, and glomerular macrophage infiltration at the end of 6 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes. | Baseline, Week 28 |
| Participants With Reduction In Proteinuria At Week 28 | Proteinuria reduction was defined as ≥ 30% decrease from baseline based on 24-hour urine protein (mg/day). | Week 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline In Proteinuria At Week 28 | Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28. | Baseline, Week 28 |
| Percent Change From Baseline In Proteinuria At Week 28 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Study Site | Aurora | Colorado | 80045 | United States | ||
| Clinical Study Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36423588 | Derived | Nester C, Appel GB, Bomback AS, Bouman KP, Cook HT, Daina E, Dixon BP, Rice K, Najafian N, Hui J, Podos SD, Langman CB, Lightstone L, Parikh SV, Pickering MC, Sperati CJ, Trachtman H, Tumlin J, de Vries AP, Wetzels JFM, Remuzzi G. Clinical Outcomes of Patients with C3G or IC-MPGN Treated with the Factor D Inhibitor Danicopan: Final Results from Two Phase 2 Studies. Am J Nephrol. 2022;53(10):687-700. doi: 10.1159/000527167. Epub 2022 Nov 24. |
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To enroll in the study, participants were required to have a biopsy confirmed diagnosis of C3 Glomerulopathy (C3G), with initial diagnosis made at least 3 months prior to dosing and significant proteinuria.
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| ID | Title | Description |
|---|---|---|
| FG000 | Danicopan (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period) | Danicopan was administered at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then dosage was to be increased to 200 mg TID for the remainder of the 6-month treatment period. All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Double-blind Treatment Period |
|
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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 | May 15, 2020 | Jun 10, 2021 |
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Investigator and participant blinded; Sponsor open. Participants were randomized 1:1 to receive either danicopan or placebo for a period of 6 months, followed by an open-label extension.
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| Placebo | Drug | Matching placebo was administered as an oral tablet. |
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Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28.
| Baseline, Week 28 |
| Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To 6 Months | Slope of eGFR was estimated using a simple linear regression for each participant, including all data values from baseline until the end of the 6-month blinded treatment period, with eGFR as the dependent variable and time as the independent variable. | 6 months |
| Slope Of Estimated Glomerular Filtration Rate (eGFR) After Open-label Danicopan Treatment | Slope of eGFR was estimated using a simple linear regression for each participant, including all data values during the open-label extension period with eGFR as the dependent variable and time as the independent variable. | 12 months |
| Change From Baseline In eGFR At Week 28 | Change from baseline in eGFR at Week 28 is presented. | Baseline, Week 28 |
| Participants With Significant Improvement In eGFR Relative To Baseline At Week 28 | Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR. | Baseline, Week 28 |
| Participants With Significant Improvement In eGFR Relative To Baseline At Week 52 | Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR. | Baseline, Week 52 |
| Lawrenceville |
| Georgia |
| 30046 |
| United States |
| Clinical Study Site | Iowa City | Iowa | 52242 | United States |
| Clinical Study Site | Baltimore | Maryland | 21205 | United States |
| Clinical Study Site | New York | New York | 10016 | United States |
| Clinical Study Site | New York | New York | 10032 | United States |
| Clinical Study Site | London | United Kingdom |
| FG001 | Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period) | Placebo was administered TID during the 6-month treatment period. All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID. |
| Received at Least 1 Dose of Study Drug |
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| COMPLETED |
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| NOT COMPLETED |
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| Open-label Extension Period |
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All participants who received at least 1 dose of study drug during the double-blind treatment period.
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| ID | Title | Description |
|---|---|---|
| BG000 | Danicopan (Double-blind Treatment Period) | Danicopan was administered at a starting dose of 100 mg 3 times daily (TID) for the first 2 weeks, then dosage was to be increased to 200 mg TID for the remainder of the 6-month treatment period. |
| BG001 | Placebo (Double-blind Treatment Period) | Placebo was administered TID during the 6-month treatment period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | 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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| 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 Composite Biopsy Score At Week 28 | The composite biopsy score was based on a score incorporating changes in the activity index, glomerular C3c staining, and glomerular macrophage infiltration at the end of 6 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes. | All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 28 |
|
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| ||||||||||||||||||||||||||||
| Primary | Participants With Reduction In Proteinuria At Week 28 | Proteinuria reduction was defined as ≥ 30% decrease from baseline based on 24-hour urine protein (mg/day). | All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints. | Posted | Number | participants | Week 28 |
|
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline In Proteinuria At Week 28 | Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28. | All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints. | Posted | Mean | Standard Deviation | mg/day | Baseline, Week 28 |
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| Secondary | Percent Change From Baseline In Proteinuria At Week 28 | Proteinuria was assessed based on 24-hour urine collections at baseline and Week 28. | All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints. | Posted | Mean | Standard Deviation | percent change | Baseline, Week 28 |
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| Secondary | Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To 6 Months | Slope of eGFR was estimated using a simple linear regression for each participant, including all data values from baseline until the end of the 6-month blinded treatment period, with eGFR as the dependent variable and time as the independent variable. | All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints. | Posted | Mean | Standard Deviation | mL/min/1.73 m^2 per month | 6 months |
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| Secondary | Slope Of Estimated Glomerular Filtration Rate (eGFR) After Open-label Danicopan Treatment | Slope of eGFR was estimated using a simple linear regression for each participant, including all data values during the open-label extension period with eGFR as the dependent variable and time as the independent variable. | All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints. | Posted | Mean | Standard Deviation | mL/min/1.73 m^2 per month | 12 months |
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| Secondary | Change From Baseline In eGFR At Week 28 | Change from baseline in eGFR at Week 28 is presented. | All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints. | Posted | Mean | Standard Deviation | mL/min/1.73 m^2 | Baseline, Week 28 |
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| Secondary | Participants With Significant Improvement In eGFR Relative To Baseline At Week 28 | Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR. | All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints. | Posted | Number | participants | Baseline, Week 28 |
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| Secondary | Participants With Significant Improvement In eGFR Relative To Baseline At Week 52 | Significant improvement relative to baseline was defined as a ≥ 20% increase from baseline in eGFR. | All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints. | Posted | Number | participants | Baseline, Week 52 |
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Day 1 (after dosing) through Week 28 (treatment period and follow-up) and Week 104 (open-label extension and follow-up). The median study duration was 548.0 days.
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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 (Double-blind Treatment Period) | Danicopan was administered at a starting dose of 100 mg TID for the first 2 weeks, then dosage was to be increased to 200 mg TID for the remainder of the 6-month treatment period. | 0 | 6 | 0 | 6 | 5 | 6 |
| EG001 | Placebo (Double-blind Treatment Period) | Placebo was administered TID during the 6-month treatment period. | 0 | 7 | 0 | 7 | 5 | 7 |
| EG002 | Danicopan (Open-label Extension Period) | All participants who received danicopan or placebo in the treatment period were to receive danicopan 200 mg TID during the open-label extension period. | 0 | 12 | 1 | 12 | 8 | 12 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute kidney injury | Renal and urinary disorders | MedDRA 22.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haematoma | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
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| Pallor | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
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| Pregnancy of partner | Social circumstances | MedDRA 22.0 | Systematic Assessment |
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| Paranasal sinus discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Feeling cold | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Pain | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Face oedema | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Nightmare | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
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| Perineal pain | Reproductive system and breast disorders | MedDRA 22.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
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| Hand fracture | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
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| Skin laceration | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
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| Joint injury | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Lower respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Dizziness postural | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Lethargy | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Memory impairment | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Eye pain | Eye disorders | MedDRA 22.0 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 22.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA 22.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Macule | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Arthropathy | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Hypothyroidism | Endocrine disorders | MedDRA 22.0 | Systematic Assessment |
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| Gout | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Dizziness | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals Inc. | Alexion Pharmaceuticals Inc. | 1 855-752-2356 | clinicaltrials@alexion.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 30, 2020 | Jun 10, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D015432 | Glomerulonephritis, Membranoproliferative |
| ID | Term |
|---|---|
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000718467 | danicopan |
| D020742 | rhoA GTP-Binding Protein |
| ID | Term |
|---|---|
| D020741 | rho GTP-Binding Proteins |
| D020559 | Monomeric GTP-Binding Proteins |
| D019204 | GTP-Binding Proteins |
| D020558 | GTP Phosphohydrolases |
| D017766 | Acid Anhydride Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D002352 | Carrier Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D047908 | Intracellular Signaling Peptides and Proteins |
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| Sponsor decision to close study |
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| Male |
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| White |
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| Other |
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| Hispanic or Latino |
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| Not Hispanic or Latino |
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| United Kingdom |
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| Week 28 |
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| Change from Baseline |
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All participants who received danicopan or placebo during the 6-month treatment period followed by danicopan 200 mg TID in the extension period. |
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| Participants |
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