Celiac Disease
Conditions
Brief summary
This study will evaluate the efficacy and safety of PRV-015 in adult patients with non-responsive celiac disease (NRCD) who are on a gluten-free diet (GFD).
Detailed description
PRV-015-002b is a Phase 2b, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of 3 dose regimens of PRV-015 in adult patients with NRCD who are on a GFD. Eligible subjects include male or female adults, 18 to 70 years of age, with a diagnosis of celiac disease and have followed a GFD for at least 12 consecutive months, yet continue to experience symptoms. Study drug (1 of the 3 doses of PRV-015 or placebo) will be administered in a double-blind fashion, followed by a safety follow-up period.
Interventions
BIOLOGICALPRV-015
Fully human monoclonal antibody against interleukin 15 (IL-15)
OTHERPlacebo
Placebo
Sponsors
Provention Bio, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* A diagnosis of celiac disease by intestinal biopsy * Following a GFD for at least 12 consecutive months * Must have detectable (above the lower limit of detection) serum celiac-related antibodies * Must have human leukocyte antigen DQ (HLA-DQ) typing consistent with celiac disease (DQ2 and/or DQ8) * Subjects must have had at least one of the following symptoms at least once per week during the month before screening: diarrhea, loose stools, abdominal pain, abdominal cramping, bloating, or gas. * Body weight between 35 and 120 kg
Exclusion criteria
* Current diagnosis of any severe complication of celiac disease, such as refractory celiac disease type 1 (RCD-I) or RCD-II, enteropathy-associated T-cell lymphoma (EATL), ulcerative jejunitis, or gastrointestinal (GI) perforation * Diagnosis of any chronic, active GI disease other than celiac disease * Presence of any active infection * Selective immunoglobulin A (IgA) deficiency, defined as having undetectable levels of IgA * Known or suspected exposure to coronavirus disease 2019 (COVID-19) infection in the 4 weeks before screening * Administration of a live vaccine within 14 days prior to randomization and the first administration of study drug * History or presence of any clinically significant disease that, in the opinion of the Investigator, may confound the subject's participation and follow-up in the clinical trial or put the subject at unnecessary risk * Females who are pregnant or planning to become pregnant during the study period, or who are currently breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Abdominal Symptoms Domain Score Through Week 24 | Baseline (average of Day -7 to Day -1) up to Week 24 | The CeD PRO questionnaire was captured daily in the eDiary. The questionnaire included 9 items: abdominal cramping, abdominal pain, bloating, gas, diarrhea, loose stool, nausea, headache and tiredness. Participants were asked to rate their symptom severity on an 11-point scale and scores range from 0 (not experiencing the symptom) to 10 (the worst possible symptom experience). Abdominal Symptoms domain included abdominal cramping, abdominal pain, bloating and gas. Total score for abdominal symptoms domain range from 0 to 40. Higher scores indicated worse outcome. Baseline abdominal symptoms domain score was defined as the average of the daily scores for the last week of the placebo run-in period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Total Gastrointestinal (GI) Score Through Week 24 | Baseline (average of Day -7 to Day -1) up to Week 24 | The CeD PRO questionnaire was captured daily in the eDiary. The questionnaire included 9 items: abdominal cramping, abdominal pain, bloating, gas, diarrhea, loose stool, nausea, headache and tiredness. Participants were asked to rate their symptom severity on an 11-point scale and scores range from 0 (not experiencing the symptom) to 10 (the worst possible symptom experience). Total GI domain included abdominal symptoms domain, diarrhea, loose stool and nausea. Total GI score range from 0 to 70. Higher scores indicated worse outcome. Baseline GI score was defined as the average of the daily scores for the last week of the placebo run-in period. |
| Absolute Change From Baseline in Intraepithelial Lymphocyte (IEL) Density at Week 24 | Baseline to Week 24 | The small intestinal mucosal inflammation was measured by IEL density using immunohistochemistry. Baseline was defined as IEL density from the esophagogastroduodenoscopy biopsy conducted during the run-in period. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days | An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was defined as any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. AESIs included severe opportunistic infections and hypersensitivity reactions of at least moderate severity. A TEAE was defined as an AE that occurred from the first dose of post-randomization study drug administration through the end of the study. |
| Number of Participants With Potentially Clinically Important Changes in Hematology | From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days | Blood samples were collected to determine the hematology laboratory important changes. CHG= Change from baseline hemoglobin. |
| Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Diarrhea and Loose Stool Domain Score Through Week 24 | Baseline (average of Day -7 to Day -1) up to Week 24 | The CeD PRO questionnaire was captured daily in the eDiary. The questionnaire included 9 items: abdominal cramping, abdominal pain, bloating, gas, diarrhea, loose stool, nausea, headache and tiredness. Participants were asked to rate their symptom severity on an 11-point scale and scores range from 0 (not experiencing the symptom) to 10 (the worst possible symptom experience). Diarrhea and loose stool domain included diarrhea and loose stool. Total score for diarrhea and loose stool domain range from 0 to 20. Higher scores indicated worse outcome. Baseline diarrhea and loose stool domain score was defined as the average of the daily scores for the last week of the placebo run-in period. |
| Number of Participants With Potentially Clinically Important Changes in Urinalysis | From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days | Urine samples were collected to determine the important changes in urine. TNTC= Too numerous to count, LPF= Low power field and HPF= High power field. |
| Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days | Participant's vital signs and body weight were examined to determine the important changes. Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate. mmHg= millimeters of mercury, DFB= Decrease from baseline and IFB= Increase from baseline. |
| Number of Participants With Anti-PRV-015 Antibodies | Baseline (Day 1) and Weeks 2, 4, 12, 22, 24 and 28 | Blood samples were collected to determine the presence of anti-drug antibodies by immunoassay. |
| Minimum Serum Concentrations (Cmin) of PRV-015 | Pre-dose on Day 1 and Weeks 2, 4, 8, 12, 16, 20, 22, 24 and 28 | Blood samples were collected at specified timepoints to determine the Cmin. |
| Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days | Blood samples were collected to determine the clinical chemistry laboratory important changes. ULN= Upper limit of normal, mmol/L= millimoles per liter and mcmol/L= micromoles per liter. |
Countries
Canada, Netherlands, Spain, United States
Participant flow
Recruitment details
The study was conducted at 39 centers in 4 countries. A total of 648 participants were screened between 24 August 2020 and 16 January 2024, of which 255 participants were screen failures and 5 participants discontinued before run-in period. Screen failures were mainly due to not meeting eligibility criteria.
Pre-assignment details
A total of 388 participants entered the single-blind placebo run-in period and among them, 1 participant never received treatment and was not started after signing the ICF, 9 participants discontinued during run-in or were not dosed, and 27 participants were considered run-in failures. Another 126 participants were considered randomization failures. A total of 226 participants were enrolled and randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Single-blind: Placebo Participants received placebo SC injection q2w in single-blind placebo run-in period for 4 weeks. | 387 |
| Double-blind: Placebo Participants received placebo matching with PRV-015 SC injection q2w in double-blind treatment period for 24 weeks. | 57 |
| Double-blind: PRV-015 100 mg Participants received PRV-015 100 mg SC injection q2w in double-blind treatment period for 24 weeks. | 56 |
| Double-blind: PRV-015 300 mg Participants received PRV-015 300 mg SC injection q2w in double-blind treatment period for 24 weeks. | 57 |
| Double-blind: PRV-015 600 mg Participants received PRV-015 600 mg SC injection q2w in double-blind treatment period for 24 weeks. | 56 |
| Total | 613 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Double-blind Period (24 Weeks) | Investigator or Sponsor judgement | 0 | 1 | 0 | 0 | 1 |
| Double-blind Period (24 Weeks) | Lost to Follow-up | 0 | 1 | 1 | 0 | 0 |
| Double-blind Period (24 Weeks) | Other | 0 | 1 | 3 | 1 | 0 |
| Double-blind Period (24 Weeks) | Withdrawal by Subject | 0 | 3 | 5 | 5 | 6 |
| Single-blind Period (4 Weeks) | Investigator or sponsor judgement | 1 | 0 | 0 | 0 | 0 |
| Single-blind Period (4 Weeks) | Not treated | 1 | 0 | 0 | 0 | 0 |
| Single-blind Period (4 Weeks) | Run-in failure | 27 | 0 | 0 | 0 | 0 |
| Single-blind Period (4 Weeks) | Withdrawal by Subject | 7 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Double-blind: PRV-015 600 mg | Total | Double-blind: PRV-015 100 mg | Double-blind: PRV-015 300 mg | Double-blind: Placebo | Single-blind: Placebo |
|---|---|---|---|---|---|---|
| Age, Continuous Double-blind period | 37.9 years STANDARD_DEVIATION 12.58 | 39.9 years STANDARD_DEVIATION 13.59 | 41.9 years STANDARD_DEVIATION 14.82 | 39.0 years STANDARD_DEVIATION 12.25 | 41.0 years STANDARD_DEVIATION 14.53 | — |
| Age, Continuous Single-blind period | — | 41.2 years STANDARD_DEVIATION 13.8 | — | — | — | 41.2 years STANDARD_DEVIATION 13.8 |
| Celiac Disease Patient Reported Outcome (CeD PRO) Abdominal Symptoms Domain Score Double-blind period Score: <3 | 13 Participants | 52 Participants | 13 Participants | 13 Participants | 13 Participants | — |
| Celiac Disease Patient Reported Outcome (CeD PRO) Abdominal Symptoms Domain Score Double-blind period Score: >=3 | 43 Participants | 174 Participants | 43 Participants | 44 Participants | 44 Participants | — |
| Celiac Disease Patient Reported Outcome (CeD PRO) Abdominal Symptoms Domain Score Single-blind period Score: <3 | — | 0 Participants | — | — | — | — |
| Celiac Disease Patient Reported Outcome (CeD PRO) Abdominal Symptoms Domain Score Single-blind period Score: >=3 | — | 0 Participants | — | — | — | — |
| Number of Participants for Stratification Factor Villous Height-to-Crypt Depth Ratio (VH:CD) Double-blind period Ratio: <2 | 36 Participants | 147 Participants | 37 Participants | 37 Participants | 37 Participants | — |
| Number of Participants for Stratification Factor Villous Height-to-Crypt Depth Ratio (VH:CD) Double-blind period Ratio: >=2 | 20 Participants | 79 Participants | 19 Participants | 20 Participants | 20 Participants | — |
| Number of Participants for Stratification Factor Villous Height-to-Crypt Depth Ratio (VH:CD) Single-blind period Ratio: <2 | — | 0 Participants | — | — | — | — |
| Number of Participants for Stratification Factor Villous Height-to-Crypt Depth Ratio (VH:CD) Single-blind period Ratio: >=2 | — | 0 Participants | — | — | — | — |
| Race/Ethnicity, Customized Double-blind period American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race/Ethnicity, Customized Double-blind period Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race/Ethnicity, Customized Double-blind period Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | — |
| Race/Ethnicity, Customized Double-blind period Multiple | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | — |
| Race/Ethnicity, Customized Double-blind period Not Reported | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race/Ethnicity, Customized Double-blind period Unknown | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race/Ethnicity, Customized Double-blind period White | 53 Participants | 221 Participants | 55 Participants | 56 Participants | 57 Participants | — |
| Race/Ethnicity, Customized Single-blind period American Indian or Alaska Native | — | 2 Participants | — | — | — | 2 Participants |
| Race/Ethnicity, Customized Single-blind period Asian | — | 1 Participants | — | — | — | 1 Participants |
| Race/Ethnicity, Customized Single-blind period Black or African American | — | 4 Participants | — | — | — | 4 Participants |
| Race/Ethnicity, Customized Single-blind period Multiple | — | 1 Participants | — | — | — | 1 Participants |
| Race/Ethnicity, Customized Single-blind period Not Reported | — | 3 Participants | — | — | — | 3 Participants |
| Race/Ethnicity, Customized Single-blind period Unknown | — | 1 Participants | — | — | — | 1 Participants |
| Race/Ethnicity, Customized Single-blind period White | — | 375 Participants | — | — | — | 375 Participants |
| Sex: Female, Male Double-blind period Female | 45 Participants | 186 Participants | 38 Participants | 50 Participants | 53 Participants | 0 Participants |
| Sex: Female, Male Double-blind period Male | 11 Participants | 40 Participants | 18 Participants | 7 Participants | 4 Participants | 0 Participants |
| Sex: Female, Male Single-blind period Female | 0 Participants | 313 Participants | 0 Participants | 0 Participants | 0 Participants | 313 Participants |
| Sex: Female, Male Single-blind period Male | 0 Participants | 74 Participants | 0 Participants | 0 Participants | 0 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 387 | 0 / 57 | 0 / 56 | 0 / 57 | 0 / 54 |
| other Total, other adverse events | 0 / 387 | 22 / 57 | 18 / 56 | 22 / 57 | 19 / 54 |
| serious Total, serious adverse events | 2 / 387 | 1 / 57 | 0 / 56 | 0 / 57 | 1 / 54 |
Outcome results
Primary
Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Abdominal Symptoms Domain Score Through Week 24
The CeD PRO questionnaire was captured daily in the eDiary. The questionnaire included 9 items: abdominal cramping, abdominal pain, bloating, gas, diarrhea, loose stool, nausea, headache and tiredness. Participants were asked to rate their symptom severity on an 11-point scale and scores range from 0 (not experiencing the symptom) to 10 (the worst possible symptom experience). Abdominal Symptoms domain included abdominal cramping, abdominal pain, bloating and gas. Total score for abdominal symptoms domain range from 0 to 40. Higher scores indicated worse outcome. Baseline abdominal symptoms domain score was defined as the average of the daily scores for the last week of the placebo run-in period.
Time frame: Baseline (average of Day -7 to Day -1) up to Week 24
Population: The modified intent-to-treat (mITT) analysis set included all randomized participants who received at least 1 dose of double-blind treatment. Only participants with data collected at baseline and up to Week 24 are reported.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Abdominal Symptoms Domain Score Through Week 24 | -1.32 score on a scale |
| PRV-015 100 mg | Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Abdominal Symptoms Domain Score Through Week 24 | -1.28 score on a scale |
| PRV-015 300 mg | Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Abdominal Symptoms Domain Score Through Week 24 | -1.21 score on a scale |
| PRV-015 600 mg | Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Abdominal Symptoms Domain Score Through Week 24 | -1.28 score on a scale |
Comparison: Estimates/p-value are from a mixed model for repeated measures (MMRM) with treatment, week, and treatment by week as fixed effects; continuous baseline CeD PRO Abdominal Symptoms domain score and baseline VH:CD ratio as covariates, and participant as a random effect.p-value: 0.854395% CI: [-0.43, 0.52]MMRM
Comparison: Estimates/p-value are from a MMRM with treatment, week, and treatment by week as fixed effects; continuous baseline CeD PRO Abdominal Symptoms domain score and baseline VH:CD ratio as covariates, and participant as a random effect.p-value: 0.655295% CI: [-0.37, 0.59]MMRM
Comparison: Estimates/p-value are from a MMRM with treatment, week, and treatment by week as fixed effects; continuous baseline CeD PRO Abdominal Symptoms domain score and baseline VH:CD ratio as covariates, and participant as a random effect.p-value: 0.870595% CI: [-0.45, 0.53]MMRM
Secondary
Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Diarrhea and Loose Stool Domain Score Through Week 24
The CeD PRO questionnaire was captured daily in the eDiary. The questionnaire included 9 items: abdominal cramping, abdominal pain, bloating, gas, diarrhea, loose stool, nausea, headache and tiredness. Participants were asked to rate their symptom severity on an 11-point scale and scores range from 0 (not experiencing the symptom) to 10 (the worst possible symptom experience). Diarrhea and loose stool domain included diarrhea and loose stool. Total score for diarrhea and loose stool domain range from 0 to 20. Higher scores indicated worse outcome. Baseline diarrhea and loose stool domain score was defined as the average of the daily scores for the last week of the placebo run-in period.
Time frame: Baseline (average of Day -7 to Day -1) up to Week 24
Population: The mITT analysis set included all randomized participants who received at least 1 dose of double-blind treatment. Only participants with data collected at baseline and up to Week 24 are reported.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Diarrhea and Loose Stool Domain Score Through Week 24 | -0.77 score on a scale |
| PRV-015 100 mg | Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Diarrhea and Loose Stool Domain Score Through Week 24 | -0.66 score on a scale |
| PRV-015 300 mg | Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Diarrhea and Loose Stool Domain Score Through Week 24 | -1.02 score on a scale |
| PRV-015 600 mg | Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Diarrhea and Loose Stool Domain Score Through Week 24 | -1.07 score on a scale |
Comparison: Estimates/p-value are from a MMRM with treatment, week, and treatment by week as fixed effects; continuous baseline CeD PRO Abdominal Symptoms domain score and baseline VH:CD ratio as covariates, and participant as a random effect.p-value: 0.675795% CI: [-0.42, 0.65]MMRM
Comparison: Estimates/p-value are from a MMRM with treatment, week, and treatment by week as fixed effects; continuous baseline CeD PRO Abdominal Symptoms domain score and baseline VH:CD ratio as covariates, and participant as a random effect.p-value: 0.364595% CI: [-0.78, 0.29]MMRM
Comparison: Estimates/p-value are from a MMRM with treatment, week, and treatment by week as fixed effects; continuous baseline CeD PRO Abdominal Symptoms domain score and baseline VH:CD ratio as covariates, and participant as a random effect.p-value: 0.279195% CI: [-0.84, 0.24]MMRM
Secondary
Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Total Gastrointestinal (GI) Score Through Week 24
The CeD PRO questionnaire was captured daily in the eDiary. The questionnaire included 9 items: abdominal cramping, abdominal pain, bloating, gas, diarrhea, loose stool, nausea, headache and tiredness. Participants were asked to rate their symptom severity on an 11-point scale and scores range from 0 (not experiencing the symptom) to 10 (the worst possible symptom experience). Total GI domain included abdominal symptoms domain, diarrhea, loose stool and nausea. Total GI score range from 0 to 70. Higher scores indicated worse outcome. Baseline GI score was defined as the average of the daily scores for the last week of the placebo run-in period.
Time frame: Baseline (average of Day -7 to Day -1) up to Week 24
Population: The mITT analysis set included all randomized participants who received at least 1 dose of double-blind treatment. Only participants with data collected at baseline and up to Week 24 are reported.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Total Gastrointestinal (GI) Score Through Week 24 | -0.89 score on a scale |
| PRV-015 100 mg | Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Total Gastrointestinal (GI) Score Through Week 24 | -0.84 score on a scale |
| PRV-015 300 mg | Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Total Gastrointestinal (GI) Score Through Week 24 | -0.88 score on a scale |
| PRV-015 600 mg | Absolute Change From Baseline in Celiac Disease Patient-Reported Outcome Total Gastrointestinal (GI) Score Through Week 24 | -1.05 score on a scale |
Comparison: Estimates/p-value are from a MMRM with treatment, week, and treatment by week as fixed effects; continuous baseline CeD PRO Abdominal Symptoms domain score and baseline VH:CD ratio as covariates, and participant as a random effect.p-value: 0.782995% CI: [-0.32, 0.42]MMRM
Comparison: Estimates/p-value are from a MMRM with treatment, week, and treatment by week as fixed effects; continuous baseline CeD PRO Abdominal Symptoms domain score and baseline VH:CD ratio as covariates, and participant as a random effect.p-value: 0.950395% CI: [-0.36, 0.38]MMRM
Comparison: Estimates/p-value are from a MMRM with treatment, week, and treatment by week as fixed effects; continuous baseline CeD PRO Abdominal Symptoms domain score and baseline VH:CD ratio as covariates, and participant as a random effect.p-value: 0.410795% CI: [-0.54, 0.22]MMRM
Secondary
Absolute Change From Baseline in Intraepithelial Lymphocyte (IEL) Density at Week 24
The small intestinal mucosal inflammation was measured by IEL density using immunohistochemistry. Baseline was defined as IEL density from the esophagogastroduodenoscopy biopsy conducted during the run-in period.
Time frame: Baseline to Week 24
Population: The mITT analysis set included all randomized participants who received at least 1 dose of double-blind treatment. Only participants with data collected at baseline and Week 24 are reported.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Absolute Change From Baseline in Intraepithelial Lymphocyte (IEL) Density at Week 24 | -0.39 cells/100 epithelial cells |
| PRV-015 100 mg | Absolute Change From Baseline in Intraepithelial Lymphocyte (IEL) Density at Week 24 | 1.54 cells/100 epithelial cells |
| PRV-015 300 mg | Absolute Change From Baseline in Intraepithelial Lymphocyte (IEL) Density at Week 24 | -4.11 cells/100 epithelial cells |
| PRV-015 600 mg | Absolute Change From Baseline in Intraepithelial Lymphocyte (IEL) Density at Week 24 | -4.53 cells/100 epithelial cells |
Comparison: Estimates/p-value are from an analysis of covariance (ANCOVA) model with treatment as a fixed effect. Continuous baseline CeD PRO Abdominal Symptoms domain score and baseline VH:CD ratio are included as covariates.p-value: 0.439795% CI: [-3, 6.87]ANCOVA
Comparison: Estimates/p-value are from an ANCOVA model with treatment as a fixed effect. Continuous baseline CeD PRO Abdominal Symptoms domain score and baseline VH:CD ratio are included as covariates.p-value: 0.133795% CI: [-8.58, 1.15]ANCOVA
Comparison: Estimates/p-value are from an ANCOVA model with treatment as a fixed effect. Continuous baseline CeD PRO Abdominal Symptoms domain score and baseline VH:CD ratio are included as covariates.p-value: 0.102195% CI: [-9.11, 0.83]ANCOVA
Secondary
Minimum Serum Concentrations (Cmin) of PRV-015
Blood samples were collected at specified timepoints to determine the Cmin.
Time frame: Pre-dose on Day 1 and Weeks 2, 4, 8, 12, 16, 20, 22, 24 and 28
Population: The Pharmacokinetic (PK) analysis set included participants who were randomized, dosed, and had at least 1 post-dose evaluable PK assessment. Only participants with data collected at specific time point are reported. Participants were not analyzed at pre-dose on Day 1 as the study drug was not administered. Hence, no data collected.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 22 | 25410 nanogram per milliliter | Geometric Coefficient of Variation 36.2 |
| Placebo | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 8 | 21790 nanogram per milliliter | Geometric Coefficient of Variation 46.4 |
| Placebo | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 24 | 26680 nanogram per milliliter | Geometric Coefficient of Variation 40.3 |
| Placebo | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 28 | 10210 nanogram per milliliter | Geometric Coefficient of Variation 58 |
| Placebo | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 4 | 15140 nanogram per milliliter | Geometric Coefficient of Variation 42.8 |
| Placebo | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 12 | 23630 nanogram per milliliter | Geometric Coefficient of Variation 46.8 |
| Placebo | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 16 | 22960 nanogram per milliliter | Geometric Coefficient of Variation 46.7 |
| Placebo | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 2 | 8778 nanogram per milliliter | Geometric Coefficient of Variation 74.1 |
| Placebo | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 20 | 27000 nanogram per milliliter | Geometric Coefficient of Variation 42.5 |
| PRV-015 100 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 20 | 74110 nanogram per milliliter | Geometric Coefficient of Variation 67.8 |
| PRV-015 100 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 22 | 73120 nanogram per milliliter | Geometric Coefficient of Variation 64.2 |
| PRV-015 100 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 12 | 73150 nanogram per milliliter | Geometric Coefficient of Variation 56.5 |
| PRV-015 100 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 4 | 51190 nanogram per milliliter | Geometric Coefficient of Variation 42.1 |
| PRV-015 100 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 24 | 72400 nanogram per milliliter | Geometric Coefficient of Variation 49.6 |
| PRV-015 100 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 8 | 61990 nanogram per milliliter | Geometric Coefficient of Variation 66.5 |
| PRV-015 100 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 2 | 27820 nanogram per milliliter | Geometric Coefficient of Variation 39.8 |
| PRV-015 100 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 28 | 32810 nanogram per milliliter | Geometric Coefficient of Variation 80 |
| PRV-015 100 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 16 | 75830 nanogram per milliliter | Geometric Coefficient of Variation 65.1 |
| PRV-015 300 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 16 | 166700 nanogram per milliliter | Geometric Coefficient of Variation 44.9 |
| PRV-015 300 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 2 | 66400 nanogram per milliliter | Geometric Coefficient of Variation 46.1 |
| PRV-015 300 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 4 | 98420 nanogram per milliliter | Geometric Coefficient of Variation 49.4 |
| PRV-015 300 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 8 | 142600 nanogram per milliliter | Geometric Coefficient of Variation 43.7 |
| PRV-015 300 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 12 | 168300 nanogram per milliliter | Geometric Coefficient of Variation 37.9 |
| PRV-015 300 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 20 | 186400 nanogram per milliliter | Geometric Coefficient of Variation 51.2 |
| PRV-015 300 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 22 | 181000 nanogram per milliliter | Geometric Coefficient of Variation 55.6 |
| PRV-015 300 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 24 | 160500 nanogram per milliliter | Geometric Coefficient of Variation 47.5 |
| PRV-015 300 mg | Minimum Serum Concentrations (Cmin) of PRV-015 | Week 28 | 69370 nanogram per milliliter | Geometric Coefficient of Variation 78.3 |
| Unknown | Minimum Serum Concentrations (Cmin) of PRV-015 | Pre-dose on Day 1 | — nanogram per milliliter | — |
Secondary
Number of Participants With Anti-PRV-015 Antibodies
Blood samples were collected to determine the presence of anti-drug antibodies by immunoassay.
Time frame: Baseline (Day 1) and Weeks 2, 4, 12, 22, 24 and 28
Population: The Immunogenicity analysis set included participants who were randomized, dosed, and had at least 1 evaluable immunogenicity assessment. Only participants with data collected at specific time point are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Anti-PRV-015 Antibodies | Week 2 | 8 Participants |
| Placebo | Number of Participants With Anti-PRV-015 Antibodies | Week 22 | 4 Participants |
| Placebo | Number of Participants With Anti-PRV-015 Antibodies | Week 12 | 4 Participants |
| Placebo | Number of Participants With Anti-PRV-015 Antibodies | Baseline | 3 Participants |
| Placebo | Number of Participants With Anti-PRV-015 Antibodies | Week 28 | 4 Participants |
| Placebo | Number of Participants With Anti-PRV-015 Antibodies | Week 24 | 4 Participants |
| Placebo | Number of Participants With Anti-PRV-015 Antibodies | Week 4 | 5 Participants |
| PRV-015 100 mg | Number of Participants With Anti-PRV-015 Antibodies | Week 12 | 5 Participants |
| PRV-015 100 mg | Number of Participants With Anti-PRV-015 Antibodies | Baseline | 8 Participants |
| PRV-015 100 mg | Number of Participants With Anti-PRV-015 Antibodies | Week 2 | 9 Participants |
| PRV-015 100 mg | Number of Participants With Anti-PRV-015 Antibodies | Week 4 | 6 Participants |
| PRV-015 100 mg | Number of Participants With Anti-PRV-015 Antibodies | Week 22 | 4 Participants |
| PRV-015 100 mg | Number of Participants With Anti-PRV-015 Antibodies | Week 24 | 3 Participants |
| PRV-015 100 mg | Number of Participants With Anti-PRV-015 Antibodies | Week 28 | 3 Participants |
| PRV-015 300 mg | Number of Participants With Anti-PRV-015 Antibodies | Week 22 | 2 Participants |
| PRV-015 300 mg | Number of Participants With Anti-PRV-015 Antibodies | Week 2 | 9 Participants |
| PRV-015 300 mg | Number of Participants With Anti-PRV-015 Antibodies | Week 28 | 2 Participants |
| PRV-015 300 mg | Number of Participants With Anti-PRV-015 Antibodies | Week 24 | 2 Participants |
| PRV-015 300 mg | Number of Participants With Anti-PRV-015 Antibodies | Week 12 | 4 Participants |
| PRV-015 300 mg | Number of Participants With Anti-PRV-015 Antibodies | Week 4 | 5 Participants |
| PRV-015 300 mg | Number of Participants With Anti-PRV-015 Antibodies | Baseline | 7 Participants |
Secondary
Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry
Blood samples were collected to determine the clinical chemistry laboratory important changes. ULN= Upper limit of normal, mmol/L= millimoles per liter and mcmol/L= micromoles per liter.
Time frame: From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days
Population: The Safety analysis set included all participants who received at least 1 dose of the study drug post-randomization. Only participants with data collected are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Potassium: >6 mmol/L | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Aspartate Aminotransferase: >=3x ULN | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Sodium: <125 mmol/L | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Chloride: >125 mmol/L | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Creatinine: >=132 mcmol/L | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Alanine Aminotransferase: >=3x ULN | 1 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Chloride: >125 mmol/L | 0 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Alanine Aminotransferase: >=3x ULN | 4 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Potassium: >6 mmol/L | 0 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Creatinine: >=132 mcmol/L | 1 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Sodium: <125 mmol/L | 0 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Aspartate Aminotransferase: >=3x ULN | 2 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Sodium: <125 mmol/L | 1 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Aspartate Aminotransferase: >=3x ULN | 0 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Creatinine: >=132 mcmol/L | 0 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Chloride: >125 mmol/L | 1 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Alanine Aminotransferase: >=3x ULN | 1 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Potassium: >6 mmol/L | 2 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Chloride: >125 mmol/L | 0 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Alanine Aminotransferase: >=3x ULN | 2 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Aspartate Aminotransferase: >=3x ULN | 0 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Sodium: <125 mmol/L | 0 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Creatinine: >=132 mcmol/L | 0 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Clinical Chemistry | Potassium: >6 mmol/L | 1 Participants |
Secondary
Number of Participants With Potentially Clinically Important Changes in Hematology
Blood samples were collected to determine the hematology laboratory important changes. CHG= Change from baseline hemoglobin.
Time frame: From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days
Population: The Safety analysis set included all participants who received at least 1 dose of the study drug post-randomization. Only participants with data collected are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Potentially Clinically Important Changes in Hematology | Hemoglobin: CHG <=-20 g/L | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Hematology | Neutrophils: <1 10^9/L | 2 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Hematology | Neutrophils: <1 10^9/L | 1 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Hematology | Hemoglobin: CHG <=-20 g/L | 0 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Hematology | Hemoglobin: CHG <=-20 g/L | 1 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Hematology | Neutrophils: <1 10^9/L | 4 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Hematology | Hemoglobin: CHG <=-20 g/L | 2 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Hematology | Neutrophils: <1 10^9/L | 2 Participants |
Secondary
Number of Participants With Potentially Clinically Important Changes in Urinalysis
Urine samples were collected to determine the important changes in urine. TNTC= Too numerous to count, LPF= Low power field and HPF= High power field.
Time frame: From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days
Population: The Safety analysis set included all participants who received at least 1 dose of the study drug post-randomization. Only participants with data collected for each specific parameter are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Ketones: 3+ | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Hyaline Casts (/HPF): Few/Moderate/Many | 3 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Glucose: 3+/4+ | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Nitrite: Positive | 2 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Crystals: Present | 3 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Bacteria: Present | 54 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Leukocytes (/HPF): Many/TNTC | 11 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Leukocyte Esterase: 3+/4+ | 19 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Erythrocytes (/HPF): Many/TNTC | 1 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Squamous Epithelial Cells (/HPF): Many/TNTC | 6 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Crystals: Present | 4 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Bacteria: Present | 51 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Erythrocytes (/HPF): Many/TNTC | 0 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Glucose: 3+/4+ | 2 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Hyaline Casts (/HPF): Few/Moderate/Many | 2 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Hyaline Casts (/LPF): Few/Moderate/Many | 1 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Ketones: 3+ | 2 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Leukocyte Esterase: 3+/4+ | 12 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Leukocytes (/HPF): Many/TNTC | 3 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Nitrite: Positive | 1 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Squamous Epithelial Cells (/HPF): Many/TNTC | 0 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Hyaline Casts (/LPF): Few/Moderate/Many | 1 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Erythrocytes (/HPF): Many/TNTC | 4 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Bacteria: Present | 55 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Ketones: 3+ | 3 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Leukocyte Esterase: 3+/4+ | 16 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Crystals: Present | 2 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Squamous Epithelial Cells (/HPF): Many/TNTC | 6 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Leukocytes (/HPF): Many/TNTC | 9 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Glucose: 3+/4+ | 1 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Nitrite: Positive | 2 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Hyaline Casts (/HPF): Few/Moderate/Many | 3 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Leukocytes (/HPF): Many/TNTC | 7 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Bacteria: Present | 47 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Squamous Epithelial Cells (/HPF): Many/TNTC | 8 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Ketones: 3+ | 1 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Crystals: Present | 5 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Leukocyte Esterase: 3+/4+ | 15 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Nitrite: Positive | 1 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Glucose: 3+/4+ | 0 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Erythrocytes (/HPF): Many/TNTC | 3 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Urinalysis | Hyaline Casts (/HPF): Few/Moderate/Many | 0 Participants |
Secondary
Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight
Participant's vital signs and body weight were examined to determine the important changes. Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate. mmHg= millimeters of mercury, DFB= Decrease from baseline and IFB= Increase from baseline.
Time frame: From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days
Population: The Safety analysis set included all participants who received at least 1 dose of the study drug post-randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | SBP: <=95 mmHg and DFB >=20 mmHg | 5 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Body weight: >=5% DFB | 8 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Heart Rate: >=120 bpm and IFB >=20 bpm | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | SBP: >=160 mmHg and IFB >=20 mmHg | 2 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Body weight: >=5% IFB | 9 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | DBP: >=110 mmHg and IFB >=10 mmHg | 0 Participants |
| Placebo | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Heart Rate: <=50 bpm and DFB >=20 bpm | 1 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Body weight: >=5% DFB | 11 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Heart Rate: <=50 bpm and DFB >=20 bpm | 1 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | DBP: >=110 mmHg and IFB >=10 mmHg | 0 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Heart Rate: >=120 bpm and IFB >=20 bpm | 0 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Body weight: >=5% IFB | 8 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | SBP: >=160 mmHg and IFB >=20 mmHg | 1 Participants |
| PRV-015 100 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | SBP: <=95 mmHg and DFB >=20 mmHg | 2 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Heart Rate: <=50 bpm and DFB >=20 bpm | 1 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | SBP: <=95 mmHg and DFB >=20 mmHg | 6 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | SBP: >=160 mmHg and IFB >=20 mmHg | 0 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | DBP: >=110 mmHg and IFB >=10 mmHg | 0 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Heart Rate: >=120 bpm and IFB >=20 bpm | 0 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Body weight: >=5% DFB | 9 Participants |
| PRV-015 300 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Body weight: >=5% IFB | 13 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | DBP: >=110 mmHg and IFB >=10 mmHg | 1 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Body weight: >=5% IFB | 5 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Body weight: >=5% DFB | 7 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | SBP: >=160 mmHg and IFB >=20 mmHg | 1 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | SBP: <=95 mmHg and DFB >=20 mmHg | 1 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Heart Rate: >=120 bpm and IFB >=20 bpm | 1 Participants |
| PRV-015 600 mg | Number of Participants With Potentially Clinically Important Changes in Vital Signs and Body Weight | Heart Rate: <=50 bpm and DFB >=20 bpm | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was defined as any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. AESIs included severe opportunistic infections and hypersensitivity reactions of at least moderate severity. A TEAE was defined as an AE that occurred from the first dose of post-randomization study drug administration through the end of the study.
Time frame: From first dose of study drug administration (Day 1) up to 28 days after the last dose administration, 197 days
Population: The Safety analysis set included all participants who received at least 1 dose of the study drug post-randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | Any TEAE | 34 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | TEAE leading to study treatment discontinuation | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | Treatment-emergent SAE | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | Treatment-emergent AESI | 2 Participants |
| PRV-015 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | TEAE leading to study treatment discontinuation | 1 Participants |
| PRV-015 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | Treatment-emergent SAE | 0 Participants |
| PRV-015 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | Treatment-emergent AESI | 1 Participants |
| PRV-015 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | Any TEAE | 34 Participants |
| PRV-015 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | Treatment-emergent SAE | 0 Participants |
| PRV-015 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | TEAE leading to study treatment discontinuation | 2 Participants |
| PRV-015 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | Treatment-emergent AESI | 1 Participants |
| PRV-015 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | Any TEAE | 36 Participants |
| PRV-015 600 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | Treatment-emergent AESI | 1 Participants |
| PRV-015 600 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | TEAE leading to study treatment discontinuation | 0 Participants |
| PRV-015 600 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | Any TEAE | 29 Participants |
| PRV-015 600 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events of Special Interest (AESIs) | Treatment-emergent SAE | 1 Participants |