Phase 2
N=147
Dose Response Study of GSK2330672 for the Treatment of Pruritus in Participants With Primary Biliary Cholangitis
Cholestasis
Bottom Line
View on ClinicalTrials.gov: NCT02966834 ↗Enrolled (actual)
147
Serious AEs
0.7%
Results posted
May 2021
Primary outcome: Primary: Mean Change From Baseline at Week 16 in the Mean Worst Daily Itch Score — -1.73; -2.19; -2.60; -2.60 Scores on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Placebo (Drug); GSK2330672 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Apr 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change From Baseline at Week 16 in the Mean Worst Daily Itch Score |
-1.73; -2.19; -2.60; -2.60; -2.86; -2.25 | — |
| SECONDARY Mean Change From Baseline at Week 16 in Primary Biliary Cholangitis-40 (PBC-40) Scale |
0.2; 0.4; 0.7; -0.9; 0.3; 0.2 | — |
| SECONDARY Mean Change From Baseline at Week 16 in Serum Alkaline Phosphatase (ALP) Concentrations, in Participants With High Risk of PBC Progression |
49.1; -57.7; -38.2; 49.6; -29.2; 19.1 | — |
| SECONDARY Number of Participants With Serum ALP Concentrations Less Than (<)1.67 Times ULN and Total Bilirubin Concentrations Less Than or Equal to (<=) ULN at Week 16 |
0; 0; 0; 0; 0; 1 | — |
| SECONDARY Mean Change From Baseline at Week 16 in Serum Alanine Aminotransferase (ALT) Among Those With a High Risk of PBC Progression |
13.0; -8.4; 0.3; -2.0; -13.5; 13.2 | — |
| SECONDARY Mean Change From Baseline at Week 16 in Serum Aspartate Aminotransferase (AST) Among Those With a High Risk of PBC Progression |
13.96; -6.04; -10.75; -8.66; -17.72; 8.16 | — |
| SECONDARY Mean Change From Baseline at Week 16 in Serum Gamma Glutamyl Transferase (GGT), Among Those With a High Risk of PBC Progression |
47.5; -58.5; -18.0; 4.6; -18.4; -6.7 | — |
| SECONDARY Mean Change From Baseline at Week 16 in Total Bilirubin Concentration, Among Those With a High Risk of PBC Progression |
1.258; -4.841; -1.079; -0.975; -0.234; 6.494 | — |
| SECONDARY Mean Change From Baseline at Week 16 in Albumin Concentration, Among Those With a High Risk of PBC Progression |
0.0; -0.5; 0.3; 0.8; 0.0; 0.7 | — |
| SECONDARY Mean Change From Baseline at Week 16 in Prothrombin International Normalized Ratio (INR), Among Those With a High Risk of PBC Progression |
0.01; -0.01; -0.03; 0.01; -0.02; -0.03 | — |
| SECONDARY Mean Change From Baseline at Week 16 in Prothrombin Time, Among Those With a High Risk of PBC Progression |
-0.10; 0.05; -0.21; 0.02; -0.18; -0.17 | — |
| SECONDARY Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) -Main Study Period |
17; 11; 19; 24; 16; 18 | — |
| SECONDARY Number of Participants With Non-SAEs and SAEs -Final Study Period |
2; 6; 8; 2; 2; 2 | — |
| SECONDARY Number of Participants With Non-SAEs and SAEs - Follow-up Period |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Clinical Chemistry Data of Potential Clinical Importance |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Hematology Data of Potential Clinical Importance |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Abnormal 12-Lead Electrocardiogram (ECG) Parameters |
10; 2; 1; 7; 8; 4 | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
-3.3; -2.1; 0.1; 0.7; -0.3; 2.0 | — |
| SECONDARY Change From Baseline in Pulse Rate |
1.5; -2.6; 1.2; -0.2; 3.4; 0.5 | — |
| SECONDARY Change From Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Assessment |
0.22; 0.15; 0.23; -0.13; -0.23; 0.22 | — |
| SECONDARY Number of Participants With Mean Worst Daily Itch Score of <4 at Week 16 |
21; 13; 14; 18; 18; 14 | — |
| SECONDARY Number of Participants With Improvement of >= 30 Percent (%) in the Mean Worst Daily Itch Score at Week 16 From Baseline |
17; 9; 15; 14; 15; 14 | — |
| SECONDARY Number of Participants With Improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 From Baseline |
14; 6; 12; 9; 13; 12 | — |
| SECONDARY Percentage of Responder Days With Worst Daily Itch Score of <4 |
40.32; 58.53; 51.38; 58.76; 65.80; 53.58 | — |
| SECONDARY Percentage of Responder Days With Improvement of >= 30% in the Mean Worst Daily Itch Score at Week 16 From Baseline |
38.46; 53.44; 45.43; 50.23; 60.29; 60.03 | — |
| SECONDARY Percentage of Responder Days With Improvement of >=2 in the Mean Worst Daily Itch Score at Week 16 From Baseline |
31.56; 37.71; 38.82; 40.69; 51.49; 58.60 | — |
| SECONDARY Change From Baseline in the Mean Daily Sleep Score at Week 16 |
-1.39; -1.66; -1.87; -1.85; -2.35; -1.69 | — |
| SECONDARY Change From Baseline in the Mean Daily Fatigue Score at Week 16 |
-0.79; -1.18; -1.19; -1.04; -1.20; -1.07 | — |
| SECONDARY Change From Baseline in the Five-Dimensional (5-D) Itch Scale at Week 16 |
-0.8; -0.9; -0.4; -1.2; -0.6; -0.7 | — |
| SECONDARY Mean Change From Baseline at Week 16 in Serum Total Bile Acid Concentration |
-4.274; -0.469; -3.878; -1.114; -2.133; 7.379 | — |
| SECONDARY Mean Change From Baseline at Week 16 in Serum 7-alpha Hydroxy-4-cholesten-3-one (C4) |
4.746; 10.703; 11.452; 29.488; 58.674; 40.629 | — |
| SECONDARY Plasma Concentration of GSK2330672 After Sparse Sampling |
5.00; 5.00; 32.71; 5.00; 358.04; 958.81 | — |
Summary
This study is being conducted to evaluate the efficacy, safety and tolerability of GSK2330672 administration for the treatment of pruritus (itch) in participants with primary biliary cholangitis (PBC). Participants will receive either placebo or one of the 4 dose regimens of GSK2330672 (20 milligram [mg], 90 mg or 180 mg taken once daily or 90 mg twice daily). Participants on GSK2330672 will also receive placebo tablets to maintain blinding. The study has a prospectively defined adaptive design that will utilize interim data to further inform and potentially optimize the doses under investigation. Hence, additional dose regimen may be added during study. The total duration of a participant in the study will be up to 45 days of screening and 24 weeks of study including follow-up.
Eligibility Criteria
Inclusion Criteria
- Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent.
- Participants who have proven PBC, as demonstrated by having at least 2 of the following: History of sustained increased ALP levels >ULN first recognized at least 6 months prior to the Screening Visit (Sustained ALP elevations at the time of Screening is not required, recognizing that the ALP may have decreased after institution of ursodeoxycholic acid (UDCA) therapy as described in inclusion number 4). Documented positive anti-mitochondrial antibody (AMA) titer (>1:40 titer on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay) or PBC-specific antinuclear antibodies (antinuclear dot and/or nuclear rim positive). Liver biopsy (at any time in the past) consistent with PBC.
- Participants must rate their itch severity as being >=4 on a 0 to 10 point scale for the majority of time (at least half the days, as recalled by the participant) during the 8 weeks prior to the Screening Visit. Periods of low itch or no itch are acceptable as long as the worst daily itch score is >=4 on the majority of days.
- Participants who are currently taking UDCA should be on stable doses of UDCA for >8 weeks at time of screening. Participants not taking UDCA due to intolerance may be enrolled 8 weeks after their last dose of UDCA. No changes or discontinuation is permitted until completion of the Main Study Period.
- Male and/or female: Female participants- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period and until at least 4 weeks after the last dose of study treatment.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria
- Screening total bilirubin >2x ULN. Total bilirubin >2x ULN is acceptable if bilirubin is fractionated and direct bilirubin 6x ULN.
- Screening eGFR =3 months before screening may be eligible for enrolment.
- Any current medical condition (e.g. psychiatric disorder, senility or dementia), which may affect the participant's ability to comply with the protocol specified procedures.
- Initiation or increase in dose of colchicine, methotrexate, azathioprine, or systemic corticosteroids in the 2 months prior to screening. If a change in dose in any of these medications is anticipated during the course of the study, the participant should be excluded.
- Initiation or increase in dose of bezafibrate or fenofibrate at any time during the 3 months prior to screening. Participants may join the study on stable doses of these medications, but no change or discontinuation is permitted until completion of the Main Study Period.
- Initiation or increase in dose of any of the following in the 8 weeks prior to screening: rifampicin, naltrexone, naloxone, nalfurafine, or sertraline. Participants may join the study on stable or decreased doses of these medications, but no change in dose is permitted until completion of the Main Study Period.
- Bile acid binding resin use: a participant must discontinue use of cholestyramine, colesevelam, colestipol or colestimide prior to the start of the Initial Study Period (no later than Day-2). Note: these drugs may be administered after completion of the Main Study Period, if clinically indicated.
- Obeticholic acid use: a participant must discontinue use of obeticholic acid at least 8 weeks prior to the start of the Initial Study Period and may not restart until after the end of the study.
- Administration of any other Inhibitor of the Human Ileal Bile Acid Transporter (IBAT) in the 3 months prior to screening.
- Current enrolment or participation within the 8 weeks before start of the Initial Study Period,
Data sourced from ClinicalTrials.gov (NCT02966834). 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.