Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Danicopan · 20 trials · 12 indications
Baseline was defined as the lowest Hgb value observed between and including Screening and Day 1. The least square (LS) mean and standard error (SE) were produced using mixed-effect model for repeated measures (MMRM). Hgb values collected within 4 weeks after transfusion were not included in the MMRM.
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.
Proteinuria reduction was defined as ≥ 30% decrease from baseline based on 24-hour urine protein (mg/day).
Serum C3 levels were measured by conventional Roche immunoturbidimetric assay method. Change from Baseline = Serum C3 levels on Day 15 - Baseline Serum C3 levels
Plasma Intact C3 level were measured by a novel multiplex assay method. Change from Baseline = Plasma Intact C3 levels on Day 15 - Baseline Plasma Intact C3 levels
Change from Baseline = Serum LDH levels on Day 28 - Baseline Serum LDH levels.
The relative bioavailability of the PIC 1 formulation versus the tablet formulation will be measured by the ratio of select pharmacokinetic (PK) parameters: maximum observed plasma concentration (Cmax), area under the concentration-time curve from time of administration to the last measurable concentration (AUC0-t), and area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf).
The relative bioavailability of the PIC 2 formulation versus the tablet formulation will be measured by the ratio of select PK parameters: Cmax, AUC0-t, and AUC0-inf.
| Arm | Type | Description |
|---|---|---|
| Danicopan | EXPERIMENTAL | Participants will receive a 12-week weight-based open-label treatment period and up to 1 year open-label long term extension period. |
| Danicopan + C5 Inhibitor | EXPERIMENTAL | Participants will receive danicopan, in addition to their C5 inhibitor therapy, for 24 weeks (12 weeks in Treatment Period 1, followed by 12 weeks in Treatment Period 2). |
| Placebo + C5 Inhibitor | PLACEBO_COMPARATOR | Participants will receive placebo, in addition to their C5 inhibitor therapy, for 12 weeks during Treatment Period 1. At Week 12, participants randomized to receive placebo will be switched to danicopan for an additional 12 weeks (Treatment Period 2). |
| 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. |
| 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. |
| Group 1: 100 mg Danicopan TID + Eculizumab | EXPERIMENTAL | Starting dose of 100 mg danicopan TID in combination with eculizumab. |
| Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab | EXPERIMENTAL | Starting dose of 100 or 150 mg danicopan TID in combination with eculizumab. |
| Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab | EXPERIMENTAL | Starting dose of 100, 150, or 200 mg danicopan TID in combination with eculizumab. |
| Group 4: Optimal Dose of Danicopan TID + Eculizumab | EXPERIMENTAL | Optimal dose (starting dose of either 100, 150, or 200 mg, as determined from Groups 1-3) of danicopan TID in combination with eculizumab. |
| Group 1: Danicopan 100 mg TID (Sentinel) | EXPERIMENTAL | All participants received 100 milligrams (mg) of danicopan three times per day (TID) during the Treatment Period. |
| Group 2: Danicopan up to 200 mg TID | EXPERIMENTAL | All participants received not more than 200 mg of danicopan TID depending on the available safety, pharmacokinetic, and pharmacodynamic data from Group 1 (Sentinel) during the Treatment Period. |
| Part 1: Sequence 1 | EXPERIMENTAL | Participants will receive danicopan once each period as a single oral dose under fasted or fed conditions as follows: Period 1: Danicopan as the PIC 1 formulation under fed conditions. Period 2: Danicopan as the PIC 1 formulation under fasted conditions. Period 3: Danicopan as a tablet under fed conditions. There will be a washout period of at least 5 days between each danicopan dosing. |
| Part 1: Sequence 2 | EXPERIMENTAL | Participants will receive danicopan once each period as a single oral dose under fasted or fed conditions as follows: Period 1: Danicopan as the PIC 1 formulation under fasted conditions. Period 2: Danicopan as a tablet under fed conditions. Period 3: Danicopan as the PIC 1 formulation under fed conditions. There will be a washout period of at least 5 days between each danicopan dosing. |
| Part 1: Sequence 3 | EXPERIMENTAL | Participants will receive danicopan once each period as a single oral dose under fasted or fed conditions as follows: Period 1: Danicopan as a tablet under fed conditions. Period 2: Danicopan as the PIC 1 formulation under fed conditions. Period 3: Danicopan as the PIC 1 formulation under fasted conditions. There will be a washout period of at least 5 days between each danicopan dosing. |
| Part 2: Sequence 1 | EXPERIMENTAL | Participants will receive danicopan once each period as a single oral dose under fasted or fed conditions as follows: Period 1: Danicopan as the PIC 2 formulation under fed conditions. Period 2: Danicopan as the PIC 2 formulation under fasted conditions. Period 3: Danicopan as a tablet under fed conditions. There will be a washout period of at least 5 days between each danicopan dosing. |
| Part 2: Sequence 2 | EXPERIMENTAL | Participants will receive danicopan once each period as a single oral dose under fasted or fed conditions as follows: Period 1: Danicopan as the PIC 2 formulation under fasted conditions. Period 2: Danicopan as a tablet under fed conditions. Period 3: Danicopan as the PIC 2 formulation under fed conditions. There will be a washout period of at least 5 days between each danicopan dosing. |
| Part 2: Sequence 3 | EXPERIMENTAL | Participants will receive danicopan once each period as a single oral dose under fasted or fed conditions as follows: Period 1: Danicopan as a tablet under fed conditions. Period 2: Danicopan as the PIC 2 formulation under fed conditions. Period 3: Danicopan as the PIC 2 formulation under fasted conditions. There will be a washout period of at least 5 days between each danicopan dosing. |
| Danicopan 200 mg Fasted | EXPERIMENTAL | Fasting participants will receive a single dose of 200 mg danicopan. |
| Danicopan 200 mg Fed | EXPERIMENTAL | Fed participants will receive a single dose of 200 mg danicopan. |
| Danicopan 400 mg Fed | EXPERIMENTAL | Fed participants will receive a single dose of 400 mg danicopan. |
| Part 2 | EXPERIMENTAL | Healthy, elderly, male participants will receive a single dose of danicopan under fed conditions. |
| Part 1: Danicopan and Warfarin | EXPERIMENTAL | Period 1: Participants received a single dose of warfarin. Period 2: Participants received danicopan three times daily, in addition to coadministration with a single dose of warfarin. Scheduled pharmacokinetics (PK) and pharmacodynamics samples were collected, with a washout period of at least 14 days between the dose of warfarin in Period 1 and the first dose of danicopan in Period 2. |
| Part 2: Danicopan and Bupropion | EXPERIMENTAL | Period 1: Participants received a single dose of bupropion. Period 2: Participants received danicopan three times daily, in addition to coadministration with a single dose of bupropion. Scheduled PK samples were collected, with a washout period of at least 7 days between the dose of bupropion in Period 1 and the first dose of danicopan in Period 2. |
| Part 3: Danicopan and EE/NET | EXPERIMENTAL | Period 1: Participants received a single dose of EE/NET. Period 2: Participants received danicopan three times daily, in addition to coadministration with a single dose of EE/NET. Scheduled PK samples were collected, with a washout period of at least 7 days between the dose of EE/NET in Period 1 and the first dose of danicopan in Period 2. |
| Part 1: Danicopan plus Cyclosporine | EXPERIMENTAL | Participants (N=14) received danicopan and cyclosporine in a fixed sequence over 2 periods: Treatment A (Period 1): 300 milligrams (mg) cyclosporine administered on Day 1. Treatment B (Period 2): 200 mg danicopan administered 3 times daily (TID) on Days 1-7 with 300 mg cyclosporine coadministered on Day 5. There was a washout period of 3 days between the dose of cyclosporine in Period 1 and the first dose of danicopan in Period 2. |
| Part 2: Danicopan plus Tacrolimus | EXPERIMENTAL | Participants (N=28) received danicopan and tacrolimus in a fixed sequence over 2 periods: Treatment C (Period 1): 2 mg tacrolimus administered on Day 1. Treatment D (Period 2): 200 mg danicopan administered TID on Days 1-10 with 2 mg tacrolimus coadministered on Day 5. There was a washout period of 7 days between the dose of tacrolimus in Period 1 and the first dose of danicopan in Period 2. |
| Part 3: Danicopan plus Antacids and Omeprazole | EXPERIMENTAL | Participants (N=30) received danicopan, calcium carbonate, aluminum/magnesium hydroxide/simethicone, and omeprazole in fixed sequences over 2 periods: Treatment E1 (Period 1): 200 mg danicopan administered TID on Days 1-4. Treatment E2 (Period 1): 200 mg danicopan coadministered with 1 gram calcium carbonate on Day 5. Treatment F1 (Period 1): 200 mg danicopan administered TID on Days 1-4. Treatment F2 (Period 1): 200 mg danicopan coadministered with 200 mg aluminum hydroxide/200 magnesium hydroxide/25 mg simethicone on Day 5. Note: Participants were randomized in a 1:1 ratio to receive either Treatment E2 or F2 coadministered with danicopan on Day 5. Treatment G1 (Period 2): 40 mg omeprazole administered once daily (QD) on Days 1-4. Treatment G2 (Period 2): 40 mg omeprazole administered QD with 200 mg danicopan administered orally TID on Days 5-8. There was a washout period of 2 days between the last dose of danicopan in Period 1 and the first dose of omeprazole in Period 2. |
| Treatment Arm (ABC) | EXPERIMENTAL | Treatment Sequence ABC - Participants received all 3 doses of danicopan in ascending fashion over 3 periods: Treatment A (Period 1): Danicopan 400 milligrams (mg) and moxifloxacin-matching placebo. Treatment B (Period 2): Danicopan 800 mg and moxifloxacin-matching placebo. Treatment C (Period 3): Danicopan 1200 mg and moxifloxacin-matching placebo. |
| Control Arm (EFG and IJK) | PLACEBO_COMPARATOR | Participants received 1 of 2 treatment sequences (Treatment Sequence EFG or Treatment Sequence IJK) over 3 periods: Treatment E (Period 1): Danicopan-matching placebo (400 mg) and moxifloxacin-matching placebo. Treatment F (Period 2): Danicopan-matching placebo (800 mg) and moxifloxacin 400 mg. Treatment G (Period 3): Danicopan-matching placebo (1200 mg) and moxifloxacin-matching placebo. Treatment I (Period 1): Danicopan-matching placebo (400 mg) and moxifloxacin 400 mg. Treatment J (Period 2): Danicopan-matching placebo (800 mg) and moxifloxacin-matching placebo. Treatment K (Period 3): Danicopan-matching placebo (1200 mg) and moxifloxacin 400 mg. |
| Part 1: Healthy Match | EXPERIMENTAL | Single 200-milligram (mg) dose of danicopan on Day 1 in healthy participants (matched control group with normal hepatic function). |
| Part 1: Moderate HI | EXPERIMENTAL | Single 200-mg dose of danicopan on Day 1 in participants with moderate HI. |
| Group 1: Matched Control Group Of Healthy Participants | EXPERIMENTAL | Participants received a single 200-milligram (mg) treatment on Day 1. |
| Group 2: Severe RI And Not On Dialysis | EXPERIMENTAL | Participants received a single 200-mg treatment on Day 1. |
| [14C]-Danicopan | EXPERIMENTAL | Participants were administered a single oral dose of danicopan between 151 and 154 mg (nominal dose of 150 mg), providing approximately 100 μCi of \[14C\] radiolabel in the form of \[14C\]-danicopan. |
| Part 1: Danicopan and Midazolam | EXPERIMENTAL | Period 1: Participants received a single dose of midazolam. Period 2: Participants received multiple doses of danicopan, in addition to coadministration with a single dose of midazolam. Scheduled pharmacokinetics (PK) blood samples were collected, with a washout period of at least 3 days between the dose in Period 1 and the first dose in Period 2. |
| Part 2: Danicopan and Fexofenadine | EXPERIMENTAL | Period 1: Participants received a single dose of fexofenadine. Period 2: Participants received multiple doses of danicopan, in addition to coadministration with a single dose of fexofenadine. Scheduled PK blood samples were collected, with a washout period of at least 3 days between the dose in Period 1 and the first dose in Period 2. |
| Part 3: Danicopan and MMF | EXPERIMENTAL | Period 1: Participants received a single dose of MMF. Period 2: Participants received multiple doses of danicopan, in addition to coadministration with a single dose of MMF. Scheduled PK blood samples were collected, with a washout period of at least 3 days between the dose in Period 1 and the first dose in Period 2. |
| Group 1: Sequence 1 | EXPERIMENTAL | Participants received danicopan once each period as a single dose under fasted or fed (medium-fat meal) conditions as follows: Period 1: Danicopan as an LFC under fasted conditions. Period 2: Danicopan as a tablet under fed (medium-fat meal) conditions. Period 3: Danicopan as a tablet under fasted conditions. There was a washout period of at least 4 days (96 hours) between each danicopan dosing. |
| Group 1: Sequence 2 | EXPERIMENTAL | Participants received danicopan once each period as a single dose under fasted or fed (medium-fat meal) conditions as follows: Period 1: Danicopan as a tablet under fed (medium-fat meal) conditions. Period 2: Danicopan as a tablet under fasted conditions. Period 3: Danicopan as an LFC under fasted conditions. There was a washout period of at least 4 days (96 hours) between each danicopan dosing. |
| Group 1: Sequence 3 | EXPERIMENTAL | Participants received danicopan once each period as a single dose under fasted or fed (medium-fat meal) conditions as follows: Period 1: Danicopan as a tablet under fasted conditions. Period 2: Danicopan as an LFC under fasted conditions. Period 3: Danicopan as a tablet under fed (medium-fat meal) conditions. There was a washout period of at least 4 days (96 hours) between each danicopan dosing. |
| Group 2: Sequence 1 | EXPERIMENTAL | Participants received danicopan once each period as a single dose under fasted conditions as follows: Period 1: Danicopan as an LFC under fasted conditions. Period 2: Danicopan as a softgel capsule under fasted conditions. There was a washout period of at least 4 days (96 hours) between each danicopan dosing. |
| Group 2: Sequence 2 | EXPERIMENTAL | Participants received danicopan once each period as a single dose under fasted conditions as follows: Period 1: Danicopan as a softgel capsule under fasted conditions. Period 2: Danicopan as an LFC under fasted conditions. There was a washout period of at least 4 days (96 hours) between each danicopan dosing. |
| Cohort 1: 200 mg | EXPERIMENTAL | All participants under fasted conditions received 200 mg of danicopan or placebo twice daily (BID) over a 14-day period. |
| Cohort 2: 500 mg | EXPERIMENTAL | All participants under fasted conditions received 500 mg of danicopan or placebo BID over a 14-day period. |
| Cohort 3: 800 mg | EXPERIMENTAL | All participants under fasted conditions received 800 mg of danicopan or placebo BID over a 14-day period. |
| Cohort 4: 75 mg | EXPERIMENTAL | All participants under fasted conditions received 75 mg of danicopan or placebo thrice daily (TID) over a 7-day period. |
| Group 1: 200 mg | EXPERIMENTAL | All participants (fasted) received either 200 mg of danicopan as a single oral dose or dose-matched placebo. |
| Group 2: 600 mg | EXPERIMENTAL | All participants (fasted) received either 600 mg of danicopan as a single oral dose or dose-matched placebo. |
| Group 3: 1200 mg | EXPERIMENTAL | All participants (fasted) received either 1200 mg of danicopan as a single oral dose or dose-matched placebo. |
| Group 4: 2400 mg | EXPERIMENTAL | All participants (fasted) received either 2400 mg of danicopan administered as 2 single doses of 1200 mg each, 12 hours apart, or dose-matched placebo. |
| Group 5: 1200 mg | EXPERIMENTAL | All participants (fed) received either 1200 mg of danicopan as a single oral dose or dose-matched placebo. |
| Name | Type | Description |
|---|---|---|
| Danicopan | DRUG | Participants will receive danicopan on a weight-based dosing regimen. |
| Placebo | DRUG | Oral tablet |
| C5 Inhibitor | DRUG | Participants will continue to receive their ongoing C5 inhibitor (eculizumab or ravulizumab) therapy according to their usual dose and schedule. |
| Eculizumab | DRUG | Participants received intravenous eculizumab administered at the participant's usual dose and schedule. |
| Danicopan: Powder-In-Capsule 1 | DRUG | Danicopan (200 milligrams) will be administered orally on Day 1. |
| Danicopan: Powder-In-Capsule 2 | DRUG | Danicopan (200 milligrams) will be administered orally on Day 1. |
| Danicopan: Tablet | DRUG | Danicopan (200 milligrams) will be administered orally on Day 1. |
| Warfarin | DRUG | Warfarin was dosed as 2 x 10 mg and 1 x 5 mg warfarin sodium tablets (Coumadin or generic equivalent). |
| Bupropion | DRUG | Bupropion was dosed as Wellbutrin (or generic equivalent) as 1 x 100 mg tablet. |
| Ethinyl Estradiol/Norethindrone | DRUG | EE/NET (0.035 mg/1 mg) was dosed as Ortho-Novum-1/35 (or generic equivalent) fixed-dose combination tablets. |
| Cyclosporine | DRUG | Oral capsule. |
| Tacrolimus | DRUG | Oral capsule. |
| Calcium Carbonate | DRUG | Chewable tablet. |
| Aluminum/Magnesium Hydroxide/Simethicone | DRUG | Chewable tablet. |
| Omeprazole | DRUG | Oral, delayed-release capsule. |
| Moxifloxacin-matching Placebo | DRUG | Moxifloxacin-matching placebo was administered as a single oral dose. |
| Danicopan-matching placebo | DRUG | Danicopan-matching placebo was administered as a single oral dose. |
| Moxifloxacin | DRUG | Moxifloxacin 400 mg was administered as a single tablet oral dose. |
| [14C]-Danicopan | DRUG | Liquid-filled capsules. |
| Midazolam | DRUG | Oral syrup. |
| Fexofenadine | DRUG | Oral tablet. |
| Mycophenolate Mofetil | DRUG | Oral tablet. |
| Danicopan - Tablet | DRUG | Oral tablet. |
| Danicopan - Softgel | DRUG | Oral softgel capsule. |
| Danicopan - LFC | DRUG | Oral LFC. |
Inclusion Criteria: * Confirmed diagnosis of PNH. * CS-EVH defined by: Anemia: Hgb ≤ 11.0 g/dL, and absolute reticulocyte count ≥ 100 × 109/L * Treated with ravulizumab or eculizumab for at least 12 weeks immediately preceding Day 1, the dose received should be stable during this period, and there ...
Danicopan is an investigational small molecule being developed for paroxysmal nocturnal hemoglobinuria (PNH), C3 glomerulopathy, and C3 glomerulonephritis. It is also studied in healthy volunteers and in hepatic impairment. Danicopan is in Phase 2 clinical development and is not yet approved by the FDA.
Danicopan is being developed by AstraZeneca PLC, which trades under the ticker AZN. The company is conducting clinical trials of Danicopan across multiple indications, including paroxysmal nocturnal hemoglobinuria and C3 glomerulopathy.
Danicopan is in Phase 2 clinical development. It is an investigational drug and has not been approved by the FDA. The development program includes completed Phase 1 trials in healthy volunteers and ongoing studies in patients with paroxysmal nocturnal hemoglobinuria and C3 glomerulopathy.
Danicopan has been studied in several clinical trials, including NCT04451434 in healthy Japanese participants, NCT04889677 and NCT04889690 in healthy adults, and NCT05109390, a drug interaction study with cyclosporine, tacrolimus, antacids, and omeprazole. These trials are all completed.
Danicopan is not known by any alternative names. It is a distinct investigational small molecule being developed by AstraZeneca for complement-mediated diseases such as paroxysmal nocturnal hemoglobinuria and C3 glomerulopathy.