Phase 2
N=36
GSK2982772 Study in Subjects With Ulcerative Colitis
Colitis, Ulcerative
Bottom Line
View on ClinicalTrials.gov: NCT02903966 ↗Enrolled (actual)
36
Serious AEs
4.2%
Results posted
Jun 2020
Primary outcome: Primary: Part A: Number of Participants With Common (>=5%) Non-serious Adverse Events (Non-SAEs) and Any Serious Adverse Events (SAEs) — 7; 13; 1; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- GSK2982772 (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Jun 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Number of Participants With Common (>=5%) Non-serious Adverse Events (Non-SAEs) and Any Serious Adverse Events (SAEs) |
7; 13; 1; 0 | — |
| PRIMARY Part B: Number of Participants With Common (>=5%) Non Serious AEs and SAEs |
7; 2 | — |
| PRIMARY Part A: Number of Participants With Worst Case Abnormal Clinical Chemistry Parameters by Potential Clinical Importance (PCI) Criteria |
0; 0; 12; 24; 0; 0 | — |
| PRIMARY Part B: Number of Participants With Worst Case Abnormal Clinical Chemistry Parameters by Potential Clinical Importance (PCI) Criteria |
0; 35; 0; 0; 35; 0 | — |
| PRIMARY Part A: Number of Participants With Worst Case Abnormal Hematology Parameters by PCI Criteria |
0; 0; 12; 24; 0; 0 | — |
| PRIMARY Part B: Number of Participants With Worst Case Abnormal Hematology Parameters by PCI Criteria |
0; 35; 0; 0; 35; 0 | — |
| PRIMARY Part A: Number of Participants With Worst Case Abnormal Urinalysis Results by Dipstick Method |
11; 24; 0; 0; 0; 0 | — |
| PRIMARY Part B: Number of Participants With Worst Case Abnormal Urinalysis Results by Dipstick Method |
34; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With Worst Case Abnormal Blood Pressure Results by PCI Criteria |
0; 0; 12; 24; 0; 0 | — |
| PRIMARY Part B: Number of Participants With Worst Case Abnormal Blood Pressure Results by PCI Criteria |
0; 34; 1; 0; 33; 2 | — |
| PRIMARY Part A: Number of Participants With Worst Case Abnormal Heart Rate (HR) Results by PCI Criteria |
0; 0; 11; 24; 1; 0 | — |
| PRIMARY Part B: Number of Participants With Worst Case Abnormal HR Results by PCI Criteria |
0; 35; 0 | — |
| PRIMARY Part A: Number of Participants With Worst-case Abnormal Electrocardiogram (ECG) Findings |
5; 11; 0; 0 | — |
| PRIMARY Part B: Number of Participants With Worst-case Abnormal ECG Findings |
18; 1 | — |
| SECONDARY Part A: Percentage of Participants Who Achieved an Absolute Mayo Endoscopy Subscore of 0 or 1 at Day 43 |
0; 4; 0; 8 | — |
| SECONDARY Part B: Percentage of Participants Who Achieved an Absolute Mayo Endoscopy Subscore of 0 or 1 at Day 85 |
0; 5; 11; 9 | — |
| SECONDARY Part A: Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Total Score |
-0.24; -0.42 | — |
| SECONDARY Part B: Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Total Score |
-0.84; -0.82 | — |
| SECONDARY Part A: Change From Baseline in Mean C Reactive Protein (CRP) |
0.25; 0.20; 1.34; -1.84; 1.06; -0.64 | — |
| SECONDARY Part B:Change From Baseline in Mean CRP |
-2.61; -2.32; -2.82; -2.71; -2.77; -1.66 | — |
| SECONDARY Part A: Change From Baseline in Fecal Calprotectin (FCP) |
0.78; 0.55; 1.23; 0.54; 1.90; 0.44 | — |
| SECONDARY Part B:Change From Baseline in FCP |
1.13; 0.56; 0.69; 0.39; 0.48; 0.40 | — |
| SECONDARY Part A: Change From Baseline in Modified Riley Scale Score (MRS) |
0.04; 0.04 | — |
| SECONDARY Part B: Change From Baseline in MRS Score |
-0.72; -0.65 | — |
| SECONDARY Part A: Change From Baseline in Geboes Index Total Score |
1.04; 0.28 | — |
| SECONDARY Part B: Change From Baseline in Geboes Index Total Score |
-0.67; -1.47 | — |
| SECONDARY Part A: Number of Participants Who Achieved Mayo Clinical Response |
4; 9 | — |
| SECONDARY Part B: Number of Participants Who Achieved Mayo Clinical Response |
5; 11 | — |
| SECONDARY Part A: Number of Participants Who Achieved Mayo Clinical Remission |
0; 0 | — |
| SECONDARY Part B: Number of Participants Who Achieved Mayo Clinical Remission |
1; 2 | — |
| SECONDARY Part A: Change From Baseline in Partial Mayo Score |
-0.68; -1.04; -1.05; -1.16; -1.30; -1.64 | — |
| SECONDARY Part B: Change From Baseline in Partial Mayo Score |
-2.87; -2.93 | — |
| SECONDARY Part A: Pre-dose Plasma Concentration of GSK2982772 |
131.749 | — |
| SECONDARY Part A: Post-dose Plasma Concentrations of GSK2982772 |
674.588; 772.043; 474.248; 481.304; 918.926; 851.391 | — |
| SECONDARY Part B: Trough Concentrations of GSK2982772 on Day 85 |
47.970; 150.642 | — |
Summary
This study is the first experience with GSK2982772, a receptor-interacting protein-1 (RIP1) kinase inhibitor, in subjects with active ulcerative colitis (UC). The primary objective will be to investigate the safety and tolerability of repeat oral doses of GSK2982772 60 mg or placebo three times daily for 42 days (Part A) followed by open label with GSK298772 60 mg three times daily for 42 days (Part B). In addition to pharmacokinetics (PK), a number of experimental and clinical endpoints will be employed to obtain information on the pharmacodynamics (PD), and preliminary efficacy in subjects with active UC. Although no formal hypothesis will be tested, these endpoints will enable a broader understanding of the mechanism of action and potential for clinical efficacy of GSK2982772 in UC. Within 30 Days of screening visit, subjects will be randomized to receive either GSK2982772 60 mg or placebo orally three times daily for 42 Days (6 weeks) in a 2:1 ratio in Part A study. Subjects who complete the Part A study will move to open label Part B study to receive GSK2982772 60 mg three times daily for an additional 42 Days (6 weeks). After the open label (Part B) treatment period, subjects will enter the Follow-up period which lasts for 28 Days (+/- 3 Days) post the last administration of study medication. The total duration of participation in the study will be approximately 20 Weeks from screening to the last study visit.
Eligibility Criteria
Inclusion Criteria
- Between 18 and 75 years of age inclusive, at the time of signing the informed consent.
- Subjects that do not have any medical conditions, other than active UC, that in the opinion of the Investigator put the subject at unacceptable risk or interfere with study assessments or integrity of the data. These medical conditions should be stable at the time of screening and are expected to remain stable for the duration of the study.
- Subject has had a confirmed diagnosis of active UC, as documented by complete diagnostic colonoscopy to the terminal ileum (TI) with biopsy performed >=3 months prior to screening. If diagnostic colonoscopy was not performed to the TI, it must be documented by the principal investigator that the subject has diffuse inflammation from the rectum extending proximally to the colon in a continuous and uniform way.
- A Complete Mayo Score of >=3 points and endoscopy sub score of 2 to 3 at screening, despite concurrent treatment with at least 1 of the following (oral corticosteroids or any oral 5-aminosalicylates (5-ASA) or purine analogues or all as defined): Oral 5-ASA at a stable dose (equivalent to >=2.4 grams per day (g/day) of Asacol) for at least 4 weeks prior to first dose. Must remain on a stable dose until end of treatment; Purine analogues (azathioprine, mercaptopurine, thiopurines) or methotrexate for at least 12 weeks prior to first dose. Must remain on a stable dose until end of treatment; Stable low dose oral corticosteroid (up to 20 mg prednisolone or equivalent) for 2 weeks prior to sigmoidoscopy. Must remain on a stable dose until end of treatment.
- If on rectal 5-ASA or corticosteroids, must remain on a stable dose for at least 4 weeks prior to first dose. Must remain on stable dose until the end of treatment.
- Subject is naive to any biological therapies for UC OR Subject may have had previous exposure to a single anti-tumor necrosis factor (TNF) biologic agent which was discontinued for reasons other than primary non-response more than 8 weeks (or 5 half-lives whichever is longer) prior to first dose OR Subject may have had previous exposure to a single biologic agent (example, vedolizumab) in the context of a previous clinical trial. The biologic agent must have been discontinued more than 8 weeks (or 5 half-lives whichever is longer) prior to first dose. Note: Exposure to a single biologic agent is not required in addition to inclusion criteria listed above (number fourth and fifth on the list).
- A body mass index (BMI) within range of 18.5 to 35 kilogram per meter square (kg/m^2) (inclusive) at screening.
- Male and Female subjects:
Males: Male subjects with female partners of child bearing potential must comply with the contraception requirements.
Females: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies:
Non-reproductive potential defined as 1) Pre-menopausal females with one of the following: Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy. 2) Postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to
Data sourced from ClinicalTrials.gov (NCT02903966). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.