Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
INCB000928 · 3 trials · 6 indications
HO will be assessed by low dose whole-body computed tomography (WBCT) (excluding the head) compared to baseline during the double-blind period.
Defined as maximum observed plasma or serum concentration, this test will assess the effect of renal impairment and hemodialysis on the exposure of single oral doses of INCB00928
Defined as area under the steady-state plasma or serum concentration-time curve over 1 dose interval, this test will assess the effect of renal impairment and hemodialysis on the exposure of single oral doses of INCB00928.
Defined as area under the single-dose plasma or serum concentration-time curve extrapolated to time of infinity, this test will assess the effect of renal impairment and hemodialysis on the exposure of single oral doses of INCB00928.
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug/treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 days after the last dose of study drug.
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 days after the last dose of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.
A DLT was defined as the occurrence of any protocol-defined toxicity occurring during the first treatment cycle, from Cycle 1 Day 1 up to and including Cycle 1 Day 28 (per regimen cycle schedule), except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. The DLT-Evaluable Population included all non-backfill participants eligible for dose escalation who met the criteria outlined in the Analysis Population field.
The MTD was defined as the dose at which the observed DLT rate was closest to the target DLT rate of 28% using an isotonical method that took the assumption of a monotonic dose-toxicity relationship into account. Per the protocol, the stopping rule was either (a) reaching a certain number of participants at one dose level under the early stopping rule or (b) reaching the pre-defined maximum sample size. Dose escalation was to be considered complete only when one of these conditions was met. After completion, the MTD was to be defined as the dose level closest to the target DLT rate. The MTD could not be concluded until the stopping rule was met.
The RDE was defined as a pharmacodynamically active dose. The RDE was determined in an independent fashion by evaluation of all available data (i.e., safety, pharmacokinetic, and pharmacodynamic data) from the respective dose-escalation stage of the study for further investigation in the expansion cohort, including safety (e.g., low-grade but chronic toxicities, dose reduction, dose interruption, or missed doses of zilurgisertib and/or ruxolitinib). The RDE(s) could not exceed the MTD in each treatment group
| Arm | Type | Description |
|---|---|---|
| Cohort 1 | EXPERIMENTAL | Participants (≥ 12 years of age) will receive INCB000928 or placebo as defined in the protocol for 24 weeks (double-blind period). Participants who complete the double-blind period will continue into open-label extension period for an additional 292 weeks. |
| Cohort 2 | EXPERIMENTAL | Participants (6 to \< 12 years of age) will receive INCB000928 or placebo as defined in the protocol for 24 weeks (double-blind period). Participants who complete the double-blind period will continue into open-label extension period for an additional 292 weeks. |
| Cohort 3 | EXPERIMENTAL | Participants (2 to \< 12 years of age) will receive INCB000928 or placebo as defined in the protocol for 24 weeks (double-blind period). Participants who complete the double-blind period will continue into open-label extension period for an additional 292 weeks. |
| Group 1: Normal Renal Function | EXPERIMENTAL | Participants with normal levels of renal function will receive a single oral dose of INCB000928 200 mg on Day 1. |
| Group 2: Mild Renal Impairment | EXPERIMENTAL | Participants with mild levels of renal impairment will receive a single oral dose of INCB000928 200 mg on Day 1. |
| Group 3: Moderate Renal Impairment | EXPERIMENTAL | Participants with moderate levels of renal impairment will receive a single oral dose of INCB000928 200 mg on Day 1. |
| Group 4: Severe Renal Impairment | EXPERIMENTAL | Participants with severe levels of renal impairment will receive a single oral dose of INCB000928 200 mg on Day 1. |
| Group 5: Kidney Failure | EXPERIMENTAL | Group 5 participants with ESRD maintained on HD will receive a single dose of INCB000928 on Day 1 of each of 2 treatment periods before (Period 1) and after (Period 2) an HD session in order to study the effects of HD on INCB000928. |
| Treatment Group A (TGA) | EXPERIMENTAL | INCB000928 will be administered once daily (QD). |
| Treatment Group B (TGB) | EXPERIMENTAL | INCB000928 will be administered in combination with ruxolitinib. |
| Treatment Group C (TGC) | EXPERIMENTAL | INCB000928 will be administered in combination with ruxolitinib. |
| Name | Type | Description |
|---|---|---|
| INCB000928 | DRUG | INCBG000928 will be administered QD orally. |
| Placebo | DRUG | Placebo will be administered QD orally. |
| ruxolitinib | DRUG | Ruxolitinib will be administered at protocol defined dose. |
Inclusion Criteria: * Female and male participants: * Cohort 1: ≥ 12 years of age. * Cohort 2: 6 to \< 12 years of age. * Cohort 3: 2 to \< 12 years of age (after eDMC review of safety data from Cohort 2). * Clinical diagnosis of FOP. * Willingness to avoid pregnancy or fathering children ba...
INCB000928 is an investigational small molecule being developed by Incyte Corporation for fibrodysplasia ossificans progressiva (FOP), anemia due to myeloproliferative disorders, and renal impairment. It is currently in clinical development, including a Phase 2 trial for FOP and Phase 1 trials for anemia and renal impairment.
INCB000928 is a small molecule being studied for its effects in conditions like fibrodysplasia ossificans progressiva and anemia. Its specific molecular target has not been disclosed in the available clinical trial information, so the exact mechanism of action is not publicly detailed.
INCB000928 is developed by Incyte Corporation, a biopharmaceutical company traded on the NASDAQ under the ticker INCY. The drug is being investigated in clinical trials for multiple indications, including fibrodysplasia ossificans progressiva and anemia.
INCB000928 is in Phase 1 and Phase 2 clinical development. It is being studied in a Phase 2 trial for fibrodysplasia ossificans progressiva and in Phase 1 trials for anemia and renal impairment. The drug is investigational and not yet approved by regulatory authorities.
INCB000928 is being studied in three clinical trials: NCT04455841, a Phase 1 trial in anemia due to myeloproliferative disorders; NCT05090891, a Phase 2 trial in fibrodysplasia ossificans progressiva; and NCT05099445, a Phase 1 trial in renal impairment and hemodialysis. These trials are conducted in multiple countries.
INCB000928 is not the same as ruxolitinib. In one clinical trial, INCB000928 is being studied as a monotherapy or in combination with ruxolitinib for anemia due to myeloproliferative disorders, indicating they are distinct drugs that may be used together.