Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as lutikizumab
ABT-981 · 10 trials · 9 indications
HiSCR 75 is defined as at least a 75% reduction from baseline in the total abscess and inflammatory nodule (AN) count, with no increase in abscess count and no increase in draining fistula count relative to baseline.
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria: 1. ≥ 50% improvement in 68-tender joint count; 2. ≥ 50% improvement in 66-swollen joint count; and 3. ≥ 50% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP)
EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
Endoscopic Improvement is defined as Mayo Endoscopic Subscore (ESS) of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal appearance of mucosa; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
HiSCR is defined as at least a 50% reduction from Baseline in the total abscess and inflammatory nodule (AN) count, with no increase in abscess count and no increase in draining fistula-count relative to Baseline.
The AUSCAN NR3.1 is a self-report measure composed of a battery of 15 questions assessing the three dimensions of pain (5 questions), joint stiffness (1 question) and physical function (9 questions) using an 11-box Numerical Rating Scale (NRS-11) from 0 (low) to 10 (high). The pain subdomain score ranges from 0 to 50; lower scores indicate better status. A decrease in the pain subdomain score represents improvement in status. Last Observation Carried Forward (LOCF): Missing responses were imputed by calculation based on the last nonmissing postbaseline component values.
The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement.
Change in synovitis of the index knee was evaluated using quantitative magnetic resonance imaging (MRI) measurements. MRI quantitative synovitis of the index knee was defined by mean synovial membrane thickness.
Semi-quantitative synovitis/effusion volume WORMS scores were scored as normal (0), \< 33% of maximum estimated distention (1), 33% - 66% of maximum estimated distention (2), or \> 66% of maximum estimated distention (3).
Collect all adverse events at each visit
Blood pressure, heart rate and body temperature
Hematology, Chemistry, and Urinalysis
ECGs done in triplicate
Cmax
Time to Cmax
AUC
| Arm | Type | Description |
|---|---|---|
| Period 1 | EXPERIMENTAL | Participants will be randomized to either Lutikizumab Dose B at baseline followed by Lutikizumab Dose A, or a matching placebo dose equivalent for both, every week through Week 16 . |
| Period 2: Lutikizumab Every Week | EXPERIMENTAL | Participants randomized to lutikizumab in Period 1 who complete Week 16 of the study will be re-randomized to lutikizumab Dose A through Week 52 |
| Period 2: Lutikizumab Every Other Week | EXPERIMENTAL | Participants randomized to lutikizumab in Period 1 who complete Week 16 of the study will be re-randomized to lutikizumab Dose A every other week though week 52 |
| Period 2: Placebo to Lutikizumab Group | EXPERIMENTAL | Participants randomized to Placebo in Period 1 who complete Week 16 of the study will initiate lutikizumab with Dose B followed by Dose A every week. |
| Period 2: Placebo to Lutikizumab Group Every Week | EXPERIMENTAL | Participants that were assigned Placebo in Period 1 and initiated lutikizumab in Period 2 will then be re-randomized to lutikizumab Dose A every week through Week 52 |
| Period 2: Placebo to Lutikizumab Group Every Other Week | EXPERIMENTAL | The participants that were assigned Placebo in Period 1 and initiated lutikizumab in Period 2 will then be re-randomized to lutikizumab Dose A every other week through Week 52 |
| Period 3: Open-label Lutikizumab | EXPERIMENTAL | Starting at Week 68 in Period 3, all participants will receive Open-label Lutikizumab every other week |
| Sub-Study: Lutikizumab Pre-Filled Pen | EXPERIMENTAL | Lutikizumab solution for injection in prefilled pen (EOW) for 60 weeks, followed by lutikizumab solution for injection in prefilled syringes (EOW) for 96 weeks. |
| Substudy 1: Lutikizumab Monotherapy | EXPERIMENTAL | Participants will be randomized to initially receive Lutikizumab Dose A followed by Lutikizumab Dose B |
| Substudy 1: Matching Placebo Monotherapy | PLACEBO_COMPARATOR | Participants will be randomized to receive a matching placebo dose equivalent to the Lutikizumab monotherapy. |
| Substudy 2: Ravagalimab Monotherapy | EXPERIMENTAL | Participants will be randomized to receive Ravagalimab |
| Substudy 2: Matching Placebo Monotherapy | PLACEBO_COMPARATOR | Participants will be randomized to receive a matching placebo dose equivalent to the Ravagalimab monotherapy |
| SubStudy 3: Lutikizumab and Ravagalimab Combination Therapy | EXPERIMENTAL | Participants will be randomized to be administered Lutikizumab and Ravagalimab doses |
| Substudy 3: Matching Placebo Combination Therapy | PLACEBO_COMPARATOR | Participants will be randomized to receive matching placebo doses equivalent to the Lutikizumab and Ravagalimab combination therapy |
| Sub-Study 1: Risankizumab Monotherapy | EXPERIMENTAL | Participants will receive Risankizumab |
| Sub-Study 1: Lutikizumab Monotherapy | EXPERIMENTAL | Participants will initially receive Lutikizumab Dose A followed by Lutikizumab Dose B every other week. |
| SubStudy 1: Lutikizumab and Risankizumab Combination Therapy | EXPERIMENTAL | Participants will be administered Lutikizumab and Risankizumab at the same time following the same dosing regimen as the monotherapy arms. |
| Substudy 1: Placebo to Lutikizumab | EXPERIMENTAL | In Period 1, participants will be receive a matching placebo Dose A at Baseline randomization, followed by matching placebo Dose B every other week starting at Week 2 for 16 weeks. At Week 16, participants that were assigned placebo will then enter Period 2 and receive open-label lutikizumab Dose A, followed by lutikizumab Dose B every other week starting at Week 18, and lutikizumab Dose C every other week starting at Week 32 until Week 52. |
| SS 1: Lutikizumab Hidradenitis Suppurativa (HS) Bio-Naïve | EXPERIMENTAL | HS Bio-naïve participants will receive Lutikizumab Dose A followed by Dose B as part of the 16 week treatment duration, with the option to enter an open-label LTE to continue to receive Lutikizumab Dose B at Week 16 and every week thereafter. |
| SS 1: Lutikizumab HS Tumor Necrosis Factor-Inadequate Response | EXPERIMENTAL | Tumor Necrosis Factor-Inadequate Response (TNF-IR) participants will receive Lutikizumab Dose A followed by Dose B as part of the 16 week treatment duration. |
| SS 2: Lutikizumab Atopic Dermatitis (AD) Bio-naïve | EXPERIMENTAL | AD Bio-naïve participants will receive Lutikizumab Dose C followed by Dose D as part of the 16 week treatment duration. |
| SS 2: Lutikizumab AD Dupilumab-Inadequate Response (IR) | EXPERIMENTAL | AD Dupilumab-IR participants will receive Lutikizumab Dose C followed by Dose D as part of the 16 week treatment duration. |
| Induction Group 1 | EXPERIMENTAL | Participants will receive Dose 1 of IV lutikizumab at Baseline followed by SC lutikizumab throughout induction. |
| Induction Group 2 | EXPERIMENTAL | Participants will receive Dose 2 of IV lutikizumab at Baseline followed by SC lutikizumab throughout induction. |
| Induction Group 3 | EXPERIMENTAL | Participants will receive adalimumab per label throughout induction. |
| Maintenance Group 1 | EXPERIMENTAL | Participants who responded to lutikizumab induction group 1 or 2 will be re-randomized. Participants in this group will receive SC lutikizumab throughout the maintenance period. |
| Maintenance Group 2 | EXPERIMENTAL | Participants who responded to lutikizumab induction group 1 or 2 will be re-randomized. Participants in this group will receive SC lutikizumab throughout the maintenance period. |
| Maintenance Adalimumab | EXPERIMENTAL | Participants who respond to adalimumab induction group 3 will continue to receive adalimumab per label in the maintenance period. |
| Maintenance Non-Responders | EXPERIMENTAL | Participants who do not respond to study drug at the end of induction period will receive SC lutikizumab in the maintenance period. |
| Optional Long-Term Extension (LTE) | EXPERIMENTAL | Participants who complete the maintenance period, are willing/able to inject study drug at home, and in whom therapeutic benefit to study drug is confirmed by the investigator, may participate in the optional 52-week LTE. |
| Main Study: Lutikizumab Dose A | EXPERIMENTAL | Lutikizumab Dose A every week |
| Main Study: Lutikizumab Dose B | EXPERIMENTAL | Lutikizumab Dose B every other week |
| Main Study: Lutikizumab Dose C | EXPERIMENTAL | Lutikizumab Dose C every other week |
| Main Study: Placebo | PLACEBO_COMPARATOR | Placebo every week |
| Sub-study: Group 1 | EXPERIMENTAL | Period 1: Lutikizumab Dose A every week. Period 2: Lutikizumab Dose A every week. |
| Sub-study: Group 2 | EXPERIMENTAL | Period 1: Lutikizumab Dose A every week. Period 2: Lutikizumab Dose A every other week. |
| Placebo | PLACEBO_COMPARATOR | Placebo for ABT-981 every two weeks (Q2W) for 24 weeks. |
| ABT-981 | EXPERIMENTAL | ABT-981 200 mg every two weeks (Q2W) for 24 weeks. |
| ABT-981 low dose | EXPERIMENTAL | 25 mg ABT-981 subcutaneous (SC) every 2 weeks (E2W) |
| ABT-981 medium dose | EXPERIMENTAL | 100 mg ABT-981 SC E2W |
| ABT-981 high dose | EXPERIMENTAL | 200 mg ABT-981 SC E2W |
| Group 1 | EXPERIMENTAL | Randomized 7 drug/2 placebo by group |
| Group 2 | EXPERIMENTAL | Randomized 7 drug/2 placebo by group |
| Group 3 | EXPERIMENTAL | Randomized 7 drug/2 placebo by group |
| Group 4 | EXPERIMENTAL | Randomized 7 drug/2 placebo by group |
| Name | Type | Description |
|---|---|---|
| Lutikizumab | DRUG | Subcutaneous injection |
| Placebo | DRUG | Subcutaneous injection |
| Ravagalimab | DRUG | Subcutaneous (SC) injection |
| Risankizumab | DRUG | Subcutaneous (SC) Injection |
| Adalimumab | DRUG | SC Injection |
| ABT-981 | BIOLOGICAL | ABT-981 administered by subcutaneous injection |
| Placebo for ABT-981 | BIOLOGICAL | Placebo for ABT-981 administered by subcutaneous injection |
Inclusion Criteria: * Diagnosis of moderate to severe HS for at least 6 months prior to Baseline as determined by the investigator (i.e., through medical history and interview of participant). * Total abscess and inflammatory nodule (AN) count of ≥ 5 at Baseline * Hidradenitis suppurativa (HS) lesi...
ABT-981 is an investigational monoclonal antibody being studied for osteoarthritis, including erosive hand osteoarthritis and knee osteoarthritis. It was developed to treat the signs and symptoms of these musculoskeletal conditions. It has not been approved for any indication and remains in clinical development.
ABT-981 targets interleukin-1 alpha and interleukin-1 beta, two forms of the IL-1 cytokine. It is an interleukin antagonist monoclonal antibody designed to bind and neutralize both IL-1α and IL-1β, which are mediators of inflammation and cartilage degradation in osteoarthritis.
ABT-981 is developed by AbbVie Inc., which trades on the New York Stock Exchange under the ticker ABBV. AbbVie sponsored the clinical trials evaluating the drug in osteoarthritis, including studies in erosive hand osteoarthritis and knee osteoarthritis.
ABT-981 is in Phase 2 clinical development. It has completed a Phase 2a trial in erosive hand osteoarthritis and a Phase 2 trial in knee osteoarthritis, along with an earlier Phase 1 pharmacokinetics study. It is investigational and has not been approved by the FDA.
ABT-981 has been evaluated in three completed trials: NCT02384538, a Phase 2a study in erosive hand osteoarthritis with 132 patients; NCT02087904, a Phase 2 study in knee osteoarthritis with 350 patients; and NCT01668511, a Phase 1 pharmacokinetics study in knee osteoarthritis with 36 patients.
No, ABT-981 is not FDA approved. It is an investigational monoclonal antibody that has completed Phase 2 clinical trials in erosive hand osteoarthritis and knee osteoarthritis. Further clinical development would be required before any potential regulatory approval.