Intrahepatic Cholestasis of Pregnancy
Conditions
Keywords
Pruritus, Itch, Itching, Cholestasis, Bile Acid, Pregnancy, Pregnant, Intrahepatic, Liver, ICP
Brief summary
Part 1 is an open-label randomized study of volixibat in patients with Intrahepatic Cholestasis of Pregnancy (ICP) and elevated serum bile acid concentrations (sBA) to evaluate safety and tolerability of two doses of volixibat. Part 2 is a double-blind, placebo controlled, study designed to evaluate the safety and efficacy of a selected volixibat dose.
Interventions
DRUGVolixibat
Oral capsules, administered twice daily. Volixibat is an ileal bile acid transporter (IBAT) inhibitor.
DRUGPlacebo
Capsules matched to study drug minus active substance.
Sponsors
Mirum Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Masking in Part 2 Only
Intervention model description
Randomized Open-label two arm study (Part 1) followed by a randomized double-blind, placebo controlled, study (Part 2)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Female aged ≥18 and ≤45 years with a viable pregnancy. 2. Provide signed informed consent as described in the protocol and willing to comply with all study visits and requirements. 3. Diagnosis of ICP. 4. (Part 2 only) Qualified level of pruritus associated with ICP, during screening.
Exclusion criteria
1. At the time of either the screening or baseline visit, decision has already been made to deliver within the next 7 days, for any indication. 2. Known non-reassuring fetal status based upon antepartum testing (e.g., NST/CTG or BPP) at or within 7 days before the baseline visit. 3. Known fetal anomaly likely to result in intrauterine fetal demise or neonatal death within the first 30 days of life. 4. Participating in another ongoing interventional clinical study at screening or planning to participate in another contemporaneous interventional clinical study while participating in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the Safety and Tolerability of Volixibat in Participants With ICP | Through to end of treatment, up to 21 weeks | To assess the safety and tolerability of volixibat in participants with ICP on the basis of the following endpoints: Proportion of participants experiencing one or more of the following: Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), events of clinical interest (ECIs), and adverse events (AEs) that lead to discontinuation of study drugs. Clinically significant laboratory abnormalities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in the Weekly Average Worst Daily Itch Score as Measured by the Adult Itch Reported Outcome (ItchRO) | Through to end of treatment, up to 21 weeks | Adult Itch Reported Outcome (ItchRO) is a 0 to 10 scale with 0 being no itch and 10 being worst possible itch where participants are responding to the following question How would you rate the worst itch you experienced over the last 24hrs? |
| Proportion of Participants Experiencing One or More of Adverse Perinatal Outcomes | At least one month after delivery. | — |
Countries
New Zealand, United Kingdom, United States
Participant flow
Recruitment details
A total of 26 participants were screened at 25 sites in 3 countries (New Zealand, United Kingdom, and United States). Of them, 4 were enrolled in the study.
Pre-assignment details
After a screening period of up to 10 days during which all procedures listed for the screening visit are completed, eligible patients diagnosed with ICP with screening sBA ≥10 μmol/L during screening or at any time during the current pregnancy were randomized with stratification in a 2-arm (1:1), open-label fashion to receive volixibat 20 mg BID or volixibat 80 mg BID. A total of 26 ICP patients were screened for the study. 22 of these patients were screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Arm 1 - Volixibat 20mg (Experimental) Participants randomized to this arm will receive volixibat 20mg twice daily.
Volixibat: Oral capsules, administered twice daily. Volixibat is an ileal bile acid transporter (IBAT) inhibitor. | 2 |
| Part 1 Arm 2 - Volixibat 80mg (Experimental) Participants randomized to this arm will receive volixibat 80mg twice daily.
Volixibat: Oral capsules, administered twice daily. Volixibat is an ileal bile acid transporter (IBAT) inhibitor. | 2 |
| Part 2 Arm 1 - Volixibat Selected Dose mg (Experimental) Participants randomized to this arm will receive volixibat selected dose (mg) twice daily.
Volixibat: Oral capsules, administered twice daily. Volixibat is an ileal bile acid transporter (IBAT) inhibitor. | 0 |
| Part 2 Arm 2 - Placebo (Placebo Comparator) Participants in this arm will receive capsules matched to the study drug minus the active volixibat substance, twice daily.
Placebo: Oral capsules, administered twice daily. Capsules matched to study drug minus active substance. | 0 |
| Total | 4 |
Baseline characteristics
| Characteristic | Part 1 Arm 1 - Volixibat 20mg (Experimental) | Part 1 Arm 2 - Volixibat 80mg (Experimental) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United Kingdom | 1 participants | 2 participants | 3 participants |
| Region of Enrollment United States | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 1 / 2 | 0 / 2 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Assess the Safety and Tolerability of Volixibat in Participants With ICP
To assess the safety and tolerability of volixibat in participants with ICP on the basis of the following endpoints: Proportion of participants experiencing one or more of the following: Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), events of clinical interest (ECIs), and adverse events (AEs) that lead to discontinuation of study drugs. Clinically significant laboratory abnormalities
Time frame: Through to end of treatment, up to 21 weeks
Population: Part 2 was early terminated due to lack of enrollment and the company's assessment of enrollment feasibility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Arm 1 - Volixibat 20mg (Experimental) | Assess the Safety and Tolerability of Volixibat in Participants With ICP | 2 participants |
| Part 1 Arm 2 - Volixibat 80mg (Experimental) | Assess the Safety and Tolerability of Volixibat in Participants With ICP | 2 participants |
Secondary
Mean Change in the Weekly Average Worst Daily Itch Score as Measured by the Adult Itch Reported Outcome (ItchRO)
Adult Itch Reported Outcome (ItchRO) is a 0 to 10 scale with 0 being no itch and 10 being worst possible itch where participants are responding to the following question How would you rate the worst itch you experienced over the last 24hrs?
Time frame: Through to end of treatment, up to 21 weeks
Population: Part 2 was early terminated due to lack of enrollment and the company's assessment of enrollment feasibility.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Arm 1 - Volixibat 20mg (Experimental) | Mean Change in the Weekly Average Worst Daily Itch Score as Measured by the Adult Itch Reported Outcome (ItchRO) | -2.5 units on a scale | Standard Deviation 2.4 |
| Part 1 Arm 2 - Volixibat 80mg (Experimental) | Mean Change in the Weekly Average Worst Daily Itch Score as Measured by the Adult Itch Reported Outcome (ItchRO) | 1.3 units on a scale | Standard Deviation 2.31 |
Secondary
Proportion of Participants Experiencing One or More of Adverse Perinatal Outcomes
Time frame: At least one month after delivery.
Population: Part 2 was early terminated due to lack of enrollment and the company's assessment of enrollment feasibility.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 Arm 1 - Volixibat 20mg (Experimental) | Proportion of Participants Experiencing One or More of Adverse Perinatal Outcomes | 0 Participants |
| Part 1 Arm 2 - Volixibat 80mg (Experimental) | Proportion of Participants Experiencing One or More of Adverse Perinatal Outcomes | 2 Participants |