Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Tulisokibart · 12 trials · 11 indications
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be reported.
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be reported.
The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for study 1 will be presented.
The percentage of participants achieving clinical remission per stool frequency/abdominal pain score (SF/APS), as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for study 1 will be presented.
The percentage of participants achieving endoscopic response, as defined by a ≥50% decrease in Simplified endoscopic score for Crohn's disease (SES-CD) from baseline for study 1 will be presented.
The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for study 1 will be presented.
The percentage of participants achieving clinical remission per SF/APS, as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for study 1 will be presented.
The percentage of participants achieving endoscopic response, as defined by a ≥50% decrease in SES-CD from baseline for study 1 will be presented.
The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for study 2 will be presented.
The percentage of participants achieving clinical remission per SF/APS, as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for study 2 will be presented.
The percentage of participants achieving endoscopic response, as defined by a ≥50% decrease in SES-CD from baseline for study 2 will be presented.
The Modified Mayo Score (MMS) is a composite score of ulcerative colitis (UC) disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: Endoscopic subscore (ES), scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); Stool frequency subscore (SFS), scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and rectal bleeding subscore (RBS), scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS.
The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS.
The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS.
ACR20 response is defined as a ≥20% improvement in a) tender joint count based on 68 joints and swollen joint count based on 66 joints (0= absent; 1= present) and b) ≥20% improvement in ≥3 of 5 components: i) Health Assessment Questionnaire Disability Index (HAQ-DI) (0=without any difficulty; 3= unable to do; a higher score=worse disability); ii) Physician Global Assessment of Disease Activity (PGA) (0= not active to 10= very active; a higher score= more active disease); iii) Patient's Global Assessment of Disease Activity (PtGA) (0= not active to 10= very active; a higher score= more active disease); iv) Patient assessment of Pain Severity (0= no pain to 10= most severe pain; a higher score = more pain); v) High-sensitivity C-reactive protein (hsCRP) blood values (lower value indicates less inflammation).
The ACR20 response is a composite measure to evaluate disease activity in RA. ACR20 response is defined as a ≥20% improvement in: a) swollen joint count (66 joints) and tender joint count (68 joints) (0= Absent; 1= Present) and b) ≥20% improvement in ≥3 of the following 5 assessments and questionnaires: i) Health Assessment Questionnaire Disability Index (HAQ-DI) (0=without any difficulty; 3= unable to do) a higher score=worse disability, ii) Physician Global Assessment of Disease Activity (PGA) (0= not active to 10= very active) a higher score= more active disease; iii) Patient's Global Assessment of Disease Activity (PtGA) (0= not active to 10= very active) a higher score= more active disease; iv) Patient assessment of Pain Severity (0= no pain to 10= most severe pain) a higher score = more pain; v) High-sensitivity C-reactive protein (hsCRP) serum values, a lower value indicates less inflammation. The proportion of participants with ACR20 response at Week 12 will be presented.
ASAS 40 is defined as a relative improvement of ≥40% and an absolute improvement of ≥2 units from baseline in ≥3 of 4 domains, with no deterioration in the fourth domain. The 4 domains include Patient Global Assessment (PtGA), total spinal pain, physical function, and morning stiffness. Each domain is measured on a 10-point numeric scale from 0 = no disease symptoms/impact to 10 = extreme disease symptoms/impact, with a higher score indicating more severe impairment.
The percentage of participants with ≥50% reduction in total abscesses and inflammatory nodules (AN) count with no increase in abscess count, and no increase in draining tunnels (ie, HiSCR50) will be reported.
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. The number of participants who experience an SAE will be reported.
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. The number of participants who discontinue due to an AE will be reported.
FVC, as measured in milliliters by spirometry, is the amount of air forcibly exhaled from the lungs after taking the deepest breath possible.
Number of participants who experienced treatment-emergent adverse events (AEs)
Number of participants who experienced serious adverse events (SAEs)
Number of participants who experienced AEs leading to discontinuation
Number of participants achieving induction of endoscopic improvement (decrease in simple endoscopy score for Crohn's disease \[SES-CD\] ≥ 50% from Baseline)
The 3-component Modified Mayo Score (MMS) ranges from 0 to 9 and is composed of endoscopic assessment, rectal bleeding (RB), and stool frequency (SF) subscores with each of the components ranging from 0 to 3, with higher scores indicating more severe disease. Clinical remission is defined as endoscopic subscore of 0 or 1, RB subscore of 0, and SF subscore of 0 or 1 and not greater than baseline. Per protocol participants in Cohort 1 were analyzed for this outcome measure.
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Reported adverse experiences used the Common Terminology for Adverse Events (CTCAE) Version 4.0. Per protocol, adverse events are reported by treatment with tulisokibart or placebo regardless of assigned cohort. Participants received identical treatment regiments regardless of cohort. The percentage of participants who experienced at least one AE is reported.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Reported adverse experiences used the Common Terminology for Adverse Events (CTCAE) Version 4.0. Per protocol, adverse events are reported by treatment with tulisokibart or placebo regardless of assigned cohort. Participants received identical treatment regiments regardless of cohort. The percentage of participants who discontinued due to an AE is reported.
Reported adverse experiences used the Common Terminology for Adverse Events (CTCAE) Version 4.0. Serious adverse events are defined as: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL), Life-threatening consequences; urgent intervention indicated, and death. Per protocol, adverse events are reported by treatment with tulisokibart or placebo regardless of assigned cohort. Participants received identical treatment regiments regardless of cohort. The percentage of participants experiencing a serious AE are presented.
Blood will be collected at pre-specified time points to determine the AUC0-inf of tulisokibart. AUC0-inf is defined as the area under concentration-time curve of tulisokibart from time zero to infinity.
Blood will be collected at pre-specified time points to determine the AUC0-last of tulisokibart. AUC0-last is defined as the area under the concentration-time curve from time zero to time of last measurable concentration of tulisokibart.
Blood will be collected at pre-specified time points to determine the Cmax of tulisokibart. Cmax is defined as the maximum concentration of tulisokibart reached.
Blood will be collected at pre-specified time points to determine the Tmax of tulisokibart. Tmax is defined as the time to maximum concentration of tulisokibart reached.
Blood will be collected at pre-specified time points to determine the CL/V of tulisokibart. CL/F is the rate at which the tulisokibart is completely removed from plasma.
Blood will be collected at pre-specified time points to determine the V/F of tulisokibart. V/F is the volume of distribution of tulisokibart.
Blood will be collected at pre-specified time points to determine the t1/2 of tulisokibart. t1/2 is defined as the time required to divide plasma concentration of tulisokibart by half.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of the study intervention, whether or not considered related to the study intervention.
Blood samples will be collected to determine the AUC0-last of tulisokibart.
Blood samples will be collected to determine the AUC0-inf of tulisokibart.
Blood samples will be collected to determine the Cmax of tulisokibart.
Blood samples will be collected to determine the Tmax of tulisokibart.
Blood samples will be collected to determine the t1/2 of tulisokibart.
Blood samples will be collected to determine the CL/F of tulisokibart.
Blood samples will be collected to determine the Vz/F of tulisokibart.
| Arm | Type | Description |
|---|---|---|
| Group 1: Low Dose Unblinded | EXPERIMENTAL | Participants receive a low dose subcutaneous (SC) tulisokibart regimen. |
| Group 2: High Dose Unblinded | EXPERIMENTAL | Participants receive a high dose SC tulisokibart regimen. |
| Group 3: High Dose Blinded | EXPERIMENTAL | Participants receive a blinded high dose SC tulisokibart regimen. |
| Group 4: Low Dose Blinded | EXPERIMENTAL | Participants receive a blinded low dose SC tulisokibart regimen. |
| Study 1: High Dose Induction, High Dose Maintenance | EXPERIMENTAL | Participants receive high dose intravenous (IV) tulisokibart, followed by a high dose subcutaneous (SC) tulisokibart regimen. |
| Study 1: High Dose Induction, Low Dose Maintenance | EXPERIMENTAL | Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen. |
| Study 1: Low Dose Induction, Low Dose Maintenance | EXPERIMENTAL | Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen. |
| Study 1: Placebo | PLACEBO_COMPARATOR | Participants receive IV placebo, followed by an SC placebo regimen. |
| Study 1: High Dose Extension | EXPERIMENTAL | Participants receive a high dose SC tulisokibart regimen. Participants may continue in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites. |
| Study 1: Low Dose Extension | EXPERIMENTAL | Participants receive a low dose SC tulisokibart and placebo regimen. Participants may continue in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites. |
| Study 2: High Dose Induction | EXPERIMENTAL | Participants receive high dose IV tulisokibart. |
| Study 2: Low Dose Induction | EXPERIMENTAL | Participants receive low dose IV tulisokibart. |
| Study 2: Placebo | PLACEBO_COMPARATOR | Participants receive IV placebo. |
| Study 2: High Dose Extension | EXPERIMENTAL | Participants receive a high dose SC tulisokibart regimen. Participants may continue in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites. |
| Study 2: Low Dose Extension | EXPERIMENTAL | Participants receive a low dose SC tulisokibart regimen. Participants may continue in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites. |
| High-Dose Regimen | EXPERIMENTAL | Participants receive a high dose of tulisokibart. |
| Medium-Dose Regimen | EXPERIMENTAL | Participants receive a medium dose of tulisokibart. |
| Low-Dose Regimen | EXPERIMENTAL | Participants receive a low dose of tulisokibart and are rerandomized at Week 16 to a medium or high dose of tulisokibart. |
| Placebo Regimen | PLACEBO_COMPARATOR | Participants receive a matched placebo dose and are rerandomized at Week 16 to a medium or high dose of tulisokibart. |
| High-dose tulisokibart | EXPERIMENTAL | Participants receive background therapy of methotrexate (MTX) PLUS a high dose of tulisokibart |
| Medium-dose tulisokibart | EXPERIMENTAL | Participants receive background therapy of MTX PLUS a medium dose of tulisokibart. |
| Low-dose tulisokibart | EXPERIMENTAL | Participants receive background therapy of MTX PLUS a low dose of tulisokibart and are rerandomized at week 12 to a medium or high dose of tulisokibart. |
| Placebo | PLACEBO_COMPARATOR | Participants receive background therapy of MTX PLUS a dose-matched tulisokibart placebo and are re-randomized at week 12 to a medium or high dose of tulisokibart. |
| Arm 1: High Dose | EXPERIMENTAL | Participants receive a high dose tulisokibart regimen. |
| Arm 2: Medium Dose | EXPERIMENTAL | Participants receive a medium dose tulisokibart regimen. |
| Arm 3: Low Dose | EXPERIMENTAL | Participants receive a low dose tulisokibart regimen. |
| Arm 4: Placebo | PLACEBO_COMPARATOR | Participants receive a placebo regimen, and are then allocated to a medium or high tulisokibart dose regimen after Week 16. |
| Tulisokibart | EXPERIMENTAL | Tulisokibart IV administered by IV infusion |
| Induction Tulisokibart | EXPERIMENTAL | During the 12-week Induction Period, participants receive tulisokibart administered by intravenous (IV) infusion at 1000 mg at Week 0 and 500 mg at Weeks 2, 6, and 10. |
| OLE Tulisokibart 100 mg | EXPERIMENTAL | After completing the 12-week Induction Period, eligible participants have the option to enter the OLE Period for up to 170 weeks. Participants are randomized into the OLE Period to receive 100 mg tulisokibart by IV infusion every 4 weeks (q4w). At the discretion of the investigator, participants may titrate up to 250 mg Q4W if disease activity is not adequately controlled. |
| OLE Tulisokibart 250 mg | EXPERIMENTAL | After completing the 12-week Induction Period, eligible participants have the option to enter the OLE Period for up to 170 weeks. Participants are randomized into the OLE Period to receive 250 mg tulisokibart by IV infusion q4w. |
| Cohort 1 Tulisokibart | EXPERIMENTAL | Participants who are CDx+ and CDx- will receive tulisokibart administered by intravenous (IV) infusion at 1000 mg on Day 1, Week 0, and 500 mg on the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks. |
| Cohort 1 Placebo | PLACEBO_COMPARATOR | Participants who are CDx+ and CDx- will receive placebo administered by intravenous (IV) infusion on Day 1, Week 0 and the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks. |
| Cohort 2 Tulisokibart | EXPERIMENTAL | Participants who are CDx+ will receive tulisokibart administered by intravenous (IV) infusion at 1000 mg on Day 1, Week 0 and 500 mg on the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks. |
| Cohort 2 Placebo | PLACEBO_COMPARATOR | Participants who are CDx+ will receive placebo administered by intravenous (IV) infusion on Day 1, Week 0 and the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks. |
| Treatment A | EXPERIMENTAL | Single dose delivered subcutaneously (SC) with an autoinjector |
| Treatment B | EXPERIMENTAL | Single dose of concentration A delivered SC with syringe and vial |
| Treatment C | EXPERIMENTAL | Single dose of concentration B delivered SC with syringe and vial |
| Tulisokibart Dose 1 Treatment Subcutaneous (SC) Injection | EXPERIMENTAL | Participants will receive a single SC injection dose of tulisokibart at dose 1 on Day 1. |
| Placebo SC Injection | PLACEBO_COMPARATOR | Participants will receive a single SC injection dose of placebo at on Day 1. |
| Tulisokibart Dose 1 Intravenous (IV) Infusion | EXPERIMENTAL | Participants will receive a single IV infusion dose of tulisokibart at dose 1 on Day 1. |
| Tulisokibart Dose 2 IV Infusion | EXPERIMENTAL | Participants will receive a single IV infusion dose of tulisokibart at dose 2 on Day 1. |
| Tulisokibart Dose 3 IV Infusion | EXPERIMENTAL | Participants will receive a single IV infusion dose of tulisokibart at dose 3 on Day 1. |
| Placebo IV Infusion | PLACEBO_COMPARATOR | Participants will receive a single IV infusion dose of placebo on Day 1. |
| Name | Type | Description |
|---|---|---|
| Tulisokibart | DRUG | Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously |
| Placebo to tulisokibart | DRUG | Placebo matching SC tulisokibart |
| IV Tulisokibart | DRUG | Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously |
| SC Tulisokibart | DRUG | Humanized monoclonal antibody that binds human TL1A, administered subcutaneously |
| IV Placebo | OTHER | Placebo matching IV tulisokibart |
| SC Placebo | OTHER | Placebo matching SC tulisokibart |
| Placebo | DRUG | Subcutaneous administration |
| Methotrexate | DRUG | Background Therapy - SC injection or oral administration. Per protocol, parenteral administration is allowed. |
| Companion diagnostic ( CDx) | DIAGNOSTIC_TEST | CDx+ or CDx- |
| Companion Diagnostic (CDx) | DIAGNOSTIC_TEST | PRA023 CDx Genotyping Assay |
| Companion Diagnostic (CDx) Testing | DEVICE | PRA023 CDx Genotyping Assay |
Inclusion Criteria: * Has participated in a qualifying tulisokibart Phase 2 or Phase 3 parent study for CD or UC * The investigator determines that the participant derives clinical benefit from continued study intervention based upon clinical evaluations performed during their parent study * A part...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Sanofi SA Sponsored ADR | SNY | 6 | PHASE3 | Duvakitug |
| Eli Lilly and Company | LLY | 8 | PHASE3 | Mirikizumab |
| AbbVie, Inc. | ABBV | 14 | PHASE3 | Risankizumab, Risankizumab On-Body Injector |
| Johnson & Johnson | JNJ | 13 | PHASE3 | Ustekinumab |
| Takeda Pharmaceutical Co. Ltd. Sponsored ADR | TAK | 17 | PHASE3 | Vedolizumab |
| Merck & Co., Inc. | MRK | 2 | PHASE3 | Tulisokibart |
| AstraZeneca PLC | AZN | 2 | PHASE2 | AZD7798 |
| Disc Medicine, Inc. | IRON | 1 | PHASE2 | DISC-0974 |
| Spyre Therapeutics, Inc | SYRE | 1 | PHASE2 | SPY001, SPY002, SPY003 |
| Abivax SA Sponsored ADR | ABVX | 1 | PHASE2 | Obefazimod |
| Palisade Bio, Inc. | PALI | 1 | PHASE1 | PALI-2108 |
| Novartis AG Sponsored ADR | NVS | 1 | - | Undisclosed |
| Amgen Inc. | AMGN | 1 | N/A | Undisclosed |
| TScan Therapeutics, Inc. | TCRX | 1 | - | Undisclosed |