Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication REZUROCK is indicated for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy. REZUROCK is a kinase inhibitor indicated for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of… FDA label
Also known as belumosudil, Rho-associated Coiled-coil Kinase 2 Inhibitor KD025, ROCK-II Inhibitor KD025, ROCK2 Inhibitor KD025, SLx 2119, Belumosudil mesylate, SAR445761, Rezurock
KD025 · 14 trials · 12 indications
Overall response rate at 24 weeks defined as the proportion of participants who achieve an overall response (PR or CR) without the requirement of new systemic therapy as per NIH consensus response criteria (2014) at Week 24.
From the date of randomization to the date of any predefined event, whichever occurs first
The proportion of responders and its 95% confidence interval (estimated by the Kaplan-Meier method) will be calculated.
PK parameter (AUC at steady state)
Proportion of participants who achieve an overall response (partial response \[PR\] or complete response \[CR\]) with up to 24 weeks of therapy (i.e. by the Week 25 or Cycle 7 Day 1 visit whichever is first), as defined by the National Institute of Health (NIH) Consensus response criteria
24-week ORR defined as the proportion of participants achieving BOS complete response (CR) or partial response (PR) based on change in FEV1 measurement per criteria of the 2014 NIH Consensus Conference.
24-week ORR defined as the proportion of participants achieving BOS complete response (CR) or partial response (PR) based on change in FEV1 measurement per criteria of the 2014 NIH Consensus Conference.
24-week progression rate is defined as the proportion of participants experiencing BOS progression based on change in FEV1 measurement per criteria of the 2014 NIH Consensus Conference.
DOR is defined as time from first documentation of response to time of first documentation of deterioration from best response (e.g., complete response \[CR\] to partial response \[PR\], or PR to Lack of response \[LR\]). As per the 2014 National Institutes of Health (NIH) Consensus Development Project for clinical trials in cGVHD criteria: CR was defined as resolution of all manifestations of cGVHD in each organ or site.PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site.LR included response status of mixed, unchanged, or progression.Mixed LR was defined as complete or partial response in at least 1 organ accompanied by progression in another organ. Unchanged LR was defined as outcomes that did not meet criteria for CR, PR, progression or mixed response. Progression LR was defined as progression in at least 1 organ or site without a response in any other organ or site. Confidence interval (CI) is calculated using Kaplan-Meier method.
The questionnaire asked participants to indicate the degree of bother that they experienced due to symptoms in 7 domains potentially affected by cGVHD. It consists of 30 items of 7 domains: skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, and mental and emotional. Each question was rated/scored as 0-not at all, 1-slightly, 2-moderately, 3-quite a bit, 4-extremely with lower values representing better outcome. A domain score was calculated for each domain by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. A total score was calculated as average of all non-missing domain scores if more than 50% of them were non-missing, ranged from 0-100. A higher score indicated more bothersome symptoms. A 7-point difference on the total score of cGVHD symptom scale was found to be clinically meaningful.
The questionnaire asked participants to indicate the degree of bother that they experienced due to symptoms in 7 domains potentially affected by cGVHD. It consisted of 30 items of 7 domains: skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, and mental and emotional. Each question was rated/scored as 0-not at all, 1-slightly, 2-moderately, 3-quite a bit, 4-extremely with lower values representing better outcome. A domain score was calculated for each domain by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. A total score was calculated as average of all non-missing domain scores if more than 50% of them were non-missing, ranged from 0-100. A higher score indicated more bothersome symptoms. A 7-point difference on the total score of cGVHD symptom scale was found to be clinically meaningful. Mean of duration of \>=7PtR is presented.
The TTNT was measured as the time from first treatment to the time of new systemic cGVHD treatment, censored by last response assessment or long term follow up assessment, whichever was the latest and available. TTNT was analyzed by the Kaplan-Meier survival method.
FFS was defined as the absence of new cGVHD systemic therapy, non-relapse mortality and recurrent malignancy (i.e. underlying disease) and was censored by last response assessment or long term follow up assessment, whichever was the latest and available. Kaplan-Meier method was used for the analysis.
OS was defined as time from first dose of belumosudil to the date of death due to any cause. CI was calculated using Kaplan-Meier method.
As per the 2014 NIH Consensus Development Project for clinical trials in cGVHD criteria: CR was defined as resolution of all manifestations of cGVHD in each organ or site. PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site.
The best response (CR, PR) for individual organs (skin, eyes, mouth, esophagus, upper gastrointestinal \[GI\], lower GI, liver, lungs, joints and fascia) was summarized. As per the 2014 NIH Consensus Development Project for clinical trials in cGVHD criteria, CR was defined as resolution of all manifestations of cGVHD in each organ or site. PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site.
Change in corticosteroid doses was analyzed by using prednisone dose equivalents. If participants were not using prednisone as the systemic corticosteroid, then the prednisone dose equivalent would be determined according to following conversion ratios: 1 mg prednisone is equivalent to: 4.0 mg Hydrocortisone; 0.8 mg Methylprednisolone; 0.15 mg Dexamethasone; 1.0 mg Prednisolone and 0.8 mg Triamcinolone. Baseline was defined as the valid and last non-missing value obtained within 28 days prior to participant receiving the first study drug in parent study (KD025-208 \[NCT02841995\] or KD025-213 \[NCT03640481\]).
The GSR assessment was performed by asking the participants to rate their disease severity of cGVHD symptoms on a 0 to 10-point numeric rating scale, where score 0 indicated 'not at all severe cGVHD symptoms' and score 10 indicated 'most severe cGVHD symptoms possible'. The response was defined using scores from 9 organs: skin, eyes, mouth, esophagus, upper GI track, lower GI tract, liver, lungs, and joints and fascia plus GSR. Baseline was defined as the valid and last non-missing value obtained within 28 days prior to participant receiving the first study drug in parent study (KD025-208 \[NCT02841995\] or KD025-213 \[NCT03640481\]). Maximal improvement from Baseline was calculated as lowest GSR score on scheduled visits minus GSR score at Baseline with possible ranges from -10 to 10. The lower the number means the better improvement in cGVHD symptoms.
An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant associated with the use of a study drug, whether or not considered drug-related. Serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, was a congenital anomaly/birth defect or was an important medical event. The severity of each AE was graded using the Common Terminology Criteria for Adverse Events version 4.03 scale. TEAEs were defined as AEs that developed, worsened or became serious during the TE period.
OR was defined as the percentage of participants with complete response (CR) or partial response (PR). The OR determination of chronic graft versus host disease (cGVHD) was based on cGVHD response assessment performed by clinicians as per the 2014 National Institutes of Health (NIH) Consensus Development Project for Clinical Trials in cGVHD criteria. CR was defined as the resolution of all manifestations in each organ or site. PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site; and cGVHD progression was defined as the clinically meaningful worsening in 1 or more organs regardless of improvement in other organs.
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TEAE period (defined as the time from the first dose of study drug up to 28 days after the last dose of study drug). TEAEs included both SAEs and non-SAEs.
Area under the plasma concentration versus time curve until the time of last quantifiable concentration
Maximum plasma concentration observed
Area under the curve from time 0 to the time of last measurable concentration
Area under the curve from time 0 extrapolated to infinity
Area under the concentration-time curve from time 0 to infinity
Area under the concentration-time curve from time 0 to the last measurable concentration
Maximum observed concentration
Time of the observed maximum concentration
Terminal elimination half-life
Time of the last measurable concentration
Apparent total clearance
Apparent volume of distribution
| Arm | Type | Description |
|---|---|---|
| Belumosudil | EXPERIMENTAL | Participants will receive belumosudil |
| best available therapy(BAT) | OTHER | Participants will receive BAT based on the Investigator's judgment |
| Placebo | PLACEBO_COMPARATOR | Participants will receive matching placebo tablets PO QD per 28-day cycles starting on Day 1 until discontinuation criteria are met or until end of study |
| Belumosudil + Azithromycin | EXPERIMENTAL | Participants will receive 200 mg belumosudil orally once daily |
| Placebo + Azithromycin | PLACEBO_COMPARATOR | Participants will receive placebo orally once daily |
| Combination therapy with two oral agents (belumosudil, ruxolitinib) | EXPERIMENTAL | Ruxolitinib monotherapy as second line treatment for up to 48 weeks. Upon documented ruxolitinib failure, patients transition to belumosudil and ruxolitinib combination 3rd line therapy for 48 weeks (i.e. 12 cycles), until progression of cGVHD, or intolerance to either agent, whichever occurs sooner. Patients will be monitored for documented individual efficacy/safety/toxicity as third line treatment in cGvHD patients. |
| Cohort A: Belumosudil + Standard of Care Medications | EXPERIMENTAL | 30 participants with bronchiolitis obliterans syndrome (BOS) will complete study procedures as follows: * Drug diary * CT scans at Cycles 3 and 7 and at End of Treatment. * Cycle 1 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone, Montelukast, and Prednisone 1x daily. * Predetermined dose of azithromycin 3 days per treatment week. * Cycle 2 - 3 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone Montelukast 1x daily. Predetermined doses of Prednisone 1x daily at treating physician's discretion. * Predetermined dose of azithromycin 3 days per treatment week. * Cycle 4 - 12 * Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. * Predetermined doses of Fluticasone and Montelukast 1x daily. * Predetermined dose of azithromycin 3 days per treatment week. |
| Cohort B: Belumosudil | EXPERIMENTAL | 15 participants with signs concerning developing BOS will complete study procedure as follows: * Drug diary * CT scans at Cycles 3 and 7 and at End of Treatment. * Cycle 1 - 12 - Day 1 - 28 of 28-day cycle: Predetermined dose of Belumosudil 1x daily. |
| Arm A: belumosudil 200 mg QD | EXPERIMENTAL | The assigned arm is per the previous study KD025-213 or study KD025-208 |
| Arm B: belumosudil 200 mg BID | EXPERIMENTAL | The assigned arm is per the previous study KD025-213 or study KD025-208 |
| Arm C: belumosudil 400 mg QD | EXPERIMENTAL | The assigned arm is per the previous study KD025-213 or study KD025-208 |
| Cohort 1: Belumosudil 200 mg QD | EXPERIMENTAL | Participants received belumosudil 200 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity, or death whichever occurred first (maximum duration: 64.2 months). |
| Cohort 2: Belumosudil 200 mg BID | EXPERIMENTAL | Participants received belumosudil 200 mg orally BID in each 28-day treatment cycle until disease progression, unacceptable toxicity, or death whichever occurred first (maximum duration: 45.9 months). |
| Cohort 3: Belumosudil 400 mg QD | EXPERIMENTAL | Participants received belumosudil 400 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity, or death whichever occurred first (maximum duration: 49.2 months). |
| belumosudil tablet，then belumosudil oral suspension | EXPERIMENTAL | belumosudil tablet in period 1, then belumosudil oral suspension in period 2. |
| belumosudil oral suspension, then belumosudil tablet | EXPERIMENTAL | belumosudil oral suspension in period 1, then belumosudil tablet in period 2. |
| Part 1 | EXPERIMENTAL | Belumosudil + UGT1A1 victim drug administered in the fed state |
| Part 2 | EXPERIMENTAL | Belumosudil + P-gp victim drug administered in the fed state |
| Part 3 | EXPERIMENTAL | Belumosudil + OATP1B1/BCRP victim drug administered in the fed state |
| Normal Hepatic Function (Group 1--Control) | EXPERIMENTAL | Matched healthy subjects with normal hepatic function |
| Mild Hepatic Impairment (Group 2) | EXPERIMENTAL | Subjects with mild hepatic impairment based on Child-Pugh Class A score of 5 or 6 |
| Moderate Hepatic Impairment (Group 3) | EXPERIMENTAL | Subjects with moderate hepatic impairment based on Child-Pugh Class B score of 7 to 9 |
| Severe Hepatic Impairment (Group 4) | EXPERIMENTAL | Subjects with severe hepatic impairment based on Child-Pugh Class C score of 10 to 14 |
| KD025 | EXPERIMENTAL | 500 mg KD025 administered orally twice daily (BID) for 28 days |
| Cohort 1 | EXPERIMENTAL | 500 mg KD025 or placebo once daily (QD) for 7 days |
| Cohort 2 | EXPERIMENTAL | 800 mg KD025 or placebo QD for 7 days |
| Cohort 3 | EXPERIMENTAL | 500 mg KD025 or placebo twice daily (BID) for 7 days |
| Cohort 4 | EXPERIMENTAL | 1000 mg KD025 or placebo QD for 7 days |
| Dose level 1 | EXPERIMENTAL | Single Oral Doses of 20 mg SLx-2119 or placebo on Day 1 |
| Dose level 2 | EXPERIMENTAL | Single Oral Doses of 40 mg SLx-2119 or placebo on Day 1 |
| Dose level 3 | EXPERIMENTAL | Single Oral Doses of 80 mg SLx-2119 or placebo on Day 1 |
| Dose level 4 | EXPERIMENTAL | Single Oral Doses of 160 mg SLx-2119 or placebo on Day 1 |
| Dose level 5 | EXPERIMENTAL | Single Oral Doses of 320 mg SLx-2119 or placebo on Day 1 |
| Dose level 6 | EXPERIMENTAL | Single Oral Doses of 640 mg SLx-2119 or placebo on Day 1 |
| Name | Type | Description |
|---|---|---|
| Belumosudil | DRUG | Pharmaceutical form:Tablet-Route of administration:oral |
| Best available therapy (BAT) | OTHER | Participants will receive BAT based on the Investigator's judgment |
| Placebo | DRUG | Pharmaceutical form:Table-Route of administration:oral |
| Prednisone | DRUG | Pharmaceutical form:Tablet-Route of administration:oral |
| Prednisolone | DRUG | Pharmaceutical form:Tablet-Route of administration:oral |
| Azithromycin | DRUG | Depends on pharmaceutical presentation, Oral |
| Ruxolitinib | DRUG | Patients receive ruxolitinib (10 mg twice daily) alone for one 28-day cycle for up to 48 weeks. Upon documentation of ruxolitinib failure, patients will begin taking belumosudil in addition to ruxolitinib, at a dose of 200 mg OD or 200 mg BID (if on a PPI) for 48 weeks total (i.e. 12 cycles), unless cGvHD progresses or side effects become intolerable. |
| Fluticasone | DRUG | Via inhalation by metered-dose inhaler. |
| Montelukast | DRUG | Leukotriene Receptor Antagonist, taken orally |
| Belumosudil 200 mg QD | DRUG | Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor. |
| Belumosudil 200 mg BID | DRUG | Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor. |
| Belumosudil 400 mg QD | DRUG | Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor. |
| Belumosudil (KD025) | DRUG | Pharmaceutical form: Capsules or Tablets Route of administration: Oral |
| UGT1A1 victim drug | DRUG | Pharmaceutical form: Tablet; Route of administration: Oral |
| P-gp victim drug | DRUG | Pharmaceutical form: Capsule; Route of administration: Oral |
| OATP1B1/BCRP victim drug | DRUG | Pharmaceutical form: Tablet; Route of administration: Oral |
| KD025 | DRUG | Single dose of 200 mg KD025 orally |
| Belumosudil mesylate | DRUG | Pharmaceutical form: capsule; Route of administration: oral |
Inclusion Criteria: * Participant must be at least 12 years of age at the time of signing the informed consent. * Participants who have undergone allo-HCT. * Participants with active moderate to severe cGVHD at the time of enrollment, defined using the NIH Consensus diagnosis and staging criteria f...
KD025 is an investigational small molecule being studied for hepatic impairment, a condition in which the liver is unable to function normally. It is being evaluated in a clinical trial that includes subjects with varying degrees of hepatic impairment as well as those with normal hepatic function.
KD025 is being developed by Sanofi, a biopharmaceutical company listed on the stock exchange under the ticker symbol SNY. The company is conducting clinical research on this investigational drug for hepatic impairment.
KD025 is in Phase 1 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities and is still undergoing clinical trials to evaluate its safety and effects in humans.
KD025 has one completed clinical trial registered under NCT04166942, titled "KD025 Hepatic Impairment Study With Normal Hepatic Function and Subjects With Varying Degrees of Hepatic Impairment." This Phase 1 study enrolled 35 participants in the United States and included healthy volunteers.
KD025 is not known to have alternative names. It is a distinct investigational small molecule being developed by Sanofi for hepatic impairment. No other names for this drug have been reported.