Primary objective:To assess the efficacy of PRV-015 in attenuating the symptoms of celiac disease in adult patients with NRCD as measured by the Abdominal Symptoms domain of the Celiac Disease Patient- Reported Outcome (CeD PRO)…
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Endpoint:
• Absolute change from baseline through Week 24 in abdominal symptoms as
measured by the Abdominal Symptoms domain of the CeD PRO questionnaire
Estimand:
• The primary estimand is the difference in the overall mean values (averaged
across 24 weeks) of each of the 3 PRV-015 treatment groups compared with
placebo of the change from baseline in the Abdominal Symptoms domain of the CeD
PRO questionnaire in the target population, regardless of compliance to study
treatment or the occurrence of intercurrent events.
Secondary outcome
Secondary efficacy endpoints:
• Absolute change from baseline through Week 24 in the Diarrhea and Loose Stool
domain of the CeD PRO
• Absolute change from baseline through Week 24 in gastrointestinal (GI)
symptoms as assessed by the Total GI score (comprising the Abdominal Symptoms
domain, the Diarrhea and Loose Stool domain, and the Nausea item) of the CeD PRO
• Absolute change from baseline to Week 24 in small intestinal mucosal
inflammation, as measured by intraepithelial lymphocyte (IEL) density using
immunohistochemistry (IHC)
Safety endpoints:
• Adverse events (AEs): treatmentemergent adverse events (TEAEs), TEAEs leading
to treatment discontinuation, and treatment-emergent serious adverse events
(SAEs)
• Treatment-emergent adverse events of special interest (AESIs)
• Potentially clinically important (PCI) changes in clinical laboratory values
(hematology, chemistry, and urinalysis), vital signs (blood pressure [BP],
heart rate, temperature, respiratory rate), and weight
• Immunogenicity, as assessed by the presence of anti-PRV-015 antibodies
PK endpoint:
• Serum PRV-015 trough concentrations (Cmin)
Background summary
Celiac disease is a systemic autoimmune disease triggered by gluten consumption
in genetically susceptible individuals. Non-responsive celiac disease (NRCD)
can be defined as persistent symptoms, signs, or laboratory abnormalities
typical of celiac disease despite at least 6-12 months of treatment with a
gluten-free diet (GFD). PRV-015 (also known as AMG 714), a monoclonal antibody
that blocks interleukin 15 (IL-15), has been shown to reduce intestinal
inflammation and improve clinical symptoms induced by gluten consumption in
celiac disease. PRV-015 may be effective as an adjunctive treatment to a GFD in
NRCD patients.
Study objective
Primary objective:
To assess the efficacy of PRV-015 in attenuating the symptoms of celiac disease
in adult patients with NRCD as measured by the Abdominal Symptoms domain of the
Celiac Disease Patient- Reported Outcome (CeD PRO) questionnaire
Secondary objectives:
• To assess the effect of treatment with
PRV-015 on other measures of disease
activity
• To assess the safety, tolerability, and
pharmacokinetics (PK) of PRV-015
when administered to adult patients with
NRCD.
Study design
Protocol PRV-015-002b is a Phase 2b, randomized, double-blind,
placebo-controlled, parallel group study to evaluate the efficacy and safety of
PRV-015 in adult patients with NRCD who are on a GFD.
After signing informed consent form (ICF), subjects will undergo screening
assessments for the study in a screening period of up to 28 days before Visit
1. The screening assessments will include the collection of demographics,
medical history, and past record of the diagnosis of celiac disease if
available. Subjects should demonstrate 1) attempted adherence to a GFD,
confirmed by a lack of strong serological positivity (<2.0 x cutoff value for
positivity), and 2) exposure to gluten contamination by presenting with
detectable serology (above the lower limit of quantitation). After initial
screening, potentially eligible subjects will enter a single-blind, placebo
run-in period for 4 weeks, starting at Visit 1.
Intervention
After the single-blind placebo run-in phase, subjects will be randomized to one
of the 4 treatment
groups in a ratio of 1:1:1:1 as follows:
• PRV-015 100 mg q2w
• PRV-015 300 mg q2w
• PRV-015 600 mg q2w
• Placebo q2w
At each visit, each subject will receive 4 injections for a total volume of 6
mL
Study burden and risks
Risks which are associated with the study drug and procedures are described in
details in the main patient Information sheet and informed consent form. The
safety profile to date suggests that the risks associated with PRV-015 are mild
and transient, and predominantly injection site reactions.
Corporate Drive 55
Bridgewater NJ 08807
US
Corporate Drive 55
Bridgewater NJ 08807
US
Listed location countries
Age
Inclusion criteria
• Adult male or females, 18-70 years of age
• 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 known
celiac disease alleles (typically 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
• 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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-000649-16-NL |
| ClinicalTrials.gov | NCT04424927 |
| CCMO | NL76464.018.21 |