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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06798454




Registration number
NCT06798454
Ethics application status
Date submitted
8/10/2024
Date registered
29/01/2025

Titles & IDs
Public title
Single Ascending Dose Study to Evaluate Safety Tolerability, Pharmacokinetics, and Pharmacodynamics of PVT201 in Healthy Subjects and Patients (PBC/PSC)
Scientific title
A Phase 1, First-In-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PVT201 Following Randomized, Double-blind, Placebo-controlled Single Ascending Doses in Healthy Subjects and Patients (PBC/PSC)
Secondary ID [1] 0 0
PVT201_C1_001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Biliary Cholangitis (PBC) 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PVT201
Other interventions - Placebo

Experimental: PVT201 - PVT201 will be administered as a single IV dose. Planned doses are:

Cohort 1 Healthy Volunteers: 0.036 mg/kg Cohort 2 Healthy Volunteers: 0.15 mg/kg Cohort 3 Healthy Volunteers: 0.60 mg/kg Cohort 4 Healthy Volunteers: 1.8 mg/kg Final Cohort PBC/PSC Patients: the highest dose that was deemed safe and well tolerated in the Healthy Volunteer cohorts

Placebo comparator: Placebo (normal saline, 0.9% sodium chloride) - All Healthy Volunteer cohorts will be administered either PVT201 or placebo in a ratio of 2:1 PVT201:placebo. Patient receiving placebo will be administered an equivalent volume of normal saline as a single IV dose.

The PBC/PSC patients in the final cohort will not be administered placebo - all patients in this cohort will receive PVT201.


Treatment: Drugs: PVT201
Navacims are a novel class of nano-particle-based therapeutics being developed for the treatment of autoimmune diseases. A navacim consists of an iron oxide core surrounded by dextran that has been linked to multiple copies of a major histocompatibility complex Class II molecule and peptide. The peptide representing a disease-associated autoantigen and its paired MHC II molecule are specific to each autoimmune disease, and will be recognized by the T-cell antigen receptor.

PVT201 is a navacim that will be used to target human PDC-reactive effector T-cells in patients with primary biliary cholangitis (PBC), converting them to Type 1 regulatory cells.

IV delivery of navacims in nonclinical models of PBC induced immune tolerance and attenuation of disease pathology without impairing normal immunity to vaccines or viral and bacterial infections.

PVT201 will be administered intravenously.

Other interventions: Placebo
Participants randomized to placebo will be administered normal saline IV.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.
Timepoint [1] 0 0
To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)
Primary outcome [2] 0 0
To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.
Timepoint [2] 0 0
To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)
Primary outcome [3] 0 0
To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.
Timepoint [3] 0 0
To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)
Primary outcome [4] 0 0
To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.
Timepoint [4] 0 0
To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)
Primary outcome [5] 0 0
To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.
Timepoint [5] 0 0
To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)
Primary outcome [6] 0 0
To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.
Timepoint [6] 0 0
To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)
Primary outcome [7] 0 0
To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.
Timepoint [7] 0 0
To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)
Primary outcome [8] 0 0
To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.
Timepoint [8] 0 0
To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)
Primary outcome [9] 0 0
To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.
Timepoint [9] 0 0
To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)
Primary outcome [10] 0 0
To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.
Timepoint [10] 0 0
To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)
Primary outcome [11] 0 0
To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.
Timepoint [11] 0 0
To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)
Primary outcome [12] 0 0
To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.
Timepoint [12] 0 0
To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)
Secondary outcome [1] 0 0
To measure the pharmacokinetics (PK) of PVT201 in plasma following a single IV dose in healthy participants and in PBC/PSC patients.
Timepoint [1] 0 0
Day 1: pre-dose and t= 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr; Day 2 = 24 hr; Day 7
Secondary outcome [2] 0 0
To measure the pharmacokinetics (PK) of PVT201 in plasma following a single IV dose in healthy participants and in PBC/PSC patients.
Timepoint [2] 0 0
Day 1: pre-dose and t= 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr; Day 2 = 24 hr; Day 7
Secondary outcome [3] 0 0
To measure the pharmacokinetics (PK) of PVT201 in plasma following a single IV dose in healthy participants and in PBC/PSC patients.
Timepoint [3] 0 0
Day 1: pre-dose and t= 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr; Day 2 = 24 hr; Day 7
Secondary outcome [4] 0 0
To measure the pharmacokinetics (PK) of PVT201 in plasma following a single IV dose in healthy participants and in PBC/PSC patients.
Timepoint [4] 0 0
Day 1: pre-dose and t= 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr; Day 2 = 24 hr; Day 7
Secondary outcome [5] 0 0
To measure the pharmacokinetics (PK) of PVT201 in plasma following a single IV dose in healthy participants and in PBC/PSC patients.
Timepoint [5] 0 0
Day 1: pre-dose and t= 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr; Day 2 = 24 hr; Day 7
Secondary outcome [6] 0 0
To measure the pharmacokinetics (PK) of PVT201 in plasma following a single IV dose in healthy participants and in PBC/PSC patients.
Timepoint [6] 0 0
Day 1: pre-dose and t= 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr; Day 2 = 24 hr; Day 7
Secondary outcome [7] 0 0
To measure the pharmacokinetics (PK) of PVT201 in plasma following a single IV dose in healthy participants and in PBC/PSC patients.
Timepoint [7] 0 0
Day 1: pre-dose and t= 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr; Day 2 = 24 hr; Day 7

Eligibility
Key inclusion criteria
HEALTHY VOLUNTEER ELIGIBILITY CRITERIA



1. Healthy male or female, aged between 18 and 65 years, inclusive at Screening.
2. Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, with body weight = 50.0 kg and < 120.0 kg.
3. Carry the HLA DRB4*0101 or DRB4*0103 allele.
4. Participant is medically healthy (in the opinion of the Investigator), as determined by pre-study medical history and without CS abnormalities.
5. Female participants must be of non-child-bearing potential, or, if of child-bearing potential:

1. Must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test on Day -1.
2. Must agree not to donate ova or attempt to become pregnant from the time of signing consent until at least 30 days after the dose of study drug.
3. If not exclusively in a same-sex relationship or abstinent as a committed lifestyle, must agree to use adequate contraception established at Screening until at least 30 days after the dose of study drug.
6. Male participants must:

1. Agree not to donate sperm from the time of signing consent until at least 90 days after the dose of study drug.
2. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception from the time of signing consent until at least 90 days after the dose of study drug.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any active infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
2. History of hypersensitivity reaction, anaphylaxis or other CS reactions or known allergy to the study drug or its ingredients including but not limited to dextran.
3. History of any clinically significant disorder which, in the opinion of the Investigator would make implementation of the protocol or interpretation of study results difficult, or that would put the participant at risk by participating in the study.
4. Participant has undergone splenectomy or thymectomy.
5. Laboratory results at Screening that indicate inadequate renal function, with estimated creatinine clearance of < 60 mL/min/1.73m2.
6. Liver function test results elevated more than 1.5-fold above the upper limit of normal for GGT, ALP, AST or ALT.
7. Total bilirubin > 1.5-fold above the upper limit of normal.
8. Use of any prescription medication within 14 days prior to the dose of study drug and/or over-the-counter medication/vitamins/supplements/herbal/plant-derived medications within 7 days prior to the dose of study drug.
9. Concurrent enrollment in another clinical study, or participation in another clinical study within 30 days prior to Screening.
10. Positive alcohol breath test at Screening, upon admission to the clinic on Day -1.
11. Positive urine drugs of abuse test at Screening, upon admission to the clinic on Day -1.
12. Participant has a positive cotinine test upon admission to the clinic on Day -1.
13. Participant is breastfeeding/lactating or pregnant, or planning to breastfeed or become pregnant during the study.
14. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C (HepC) virus antibody, or human immunodeficiency (HIV) antibody tests.
15. Known substance abuse or medical, psychological, or social conditions that in the opinion of the study doctor would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

PBC/PSC PATIENT ELIGIBILITY CRITERIA

Inclusion Criteria:

1. Male or female, aged between 18 and 75 years, inclusive at Screening.
2. Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, with body weight = 50.0 kg and < 120.0 kg.
3. Carry the HLA DRB4*0101 or DRB4*0103 allele.
4. Participant is medically healthy (in the opinion of the Investigator), as determined by pre-study medical history and without CS abnormalities.
5. Male or female with a diagnosis of primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC).
6. For subjects on any medication used to treat the symptoms of PBC or PSC (examples: UDCA, OCA, seladelpar), subjects must be on a stable dose for a minimum of 3 months prior to Day 1 and expected to stay on treatment for duration of study participation OR must have been off treatment for at least 3 months prior to Day 1.
7. Subjects with inflammatory bowel disease (IBD) must have been on stable therapy > 3 months prior to Day 1.
8. Female participants must be of non-child-bearing potential, or, if of child-bearing potential:

1. Must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test on Day -1,
2. Must agree not to donate ova or attempt to become pregnant from the time of signing consent until at least 30 days after the dose of study drug,
3. If not exclusively in a same-sex relationship or abstinent as a committed lifestyle, must agree to use adequate contraception established at Screening until at least 30 days after the dose of study drug.
9. Male participants must:

1. Agree not to donate sperm from the time of signing consent until at least 90 days after the dose of study drug,
2. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception from the time of signing consent until at least 90 days after the dose of study drug.



1. Current or a history of hepatic decompensation events.
2. Subject is diagnosed with Gilbert's Syndrome.
3. Subjects who have previously undergone liver transplantation.
4. History of ileectomy, colostomy, colectomy, splenectomy, or thymectomy.
5. Any active infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
6. Co-existing liver or biliary diseases, such as choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis (NASH), acute infection of bile duct system or gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension), cirrhosis, hepatorenal syndrome, cholangiocarcinoma diagnosed or suspected liver cancers.
7. Presence of conditions that may cause non-hepatogenic ALP elevations (eg, Paget's disease) or conditions that may lead to a life expectancy of less than 2 years.
8. History of malignancy except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
9. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C (HepC) virus antibody, or human immunodeficiency (HIV) antibody tests.
10. Laboratory Screening Results:

1. AST >5 x ULN,
2. ALT >5 x ULN,
3. ALP > 10 x ULN,
4. Total bilirubin > 1.5 x ULN,
5. Albumin < 35 g/L,
6. Total white blood cells (WBC) <3000 cells/mm3,
7. Absolute neutrophil count (ANC) <1500 cells/mm3,
8. Platelet count <130,000/mm3, unless on stable anticoagulants at the discretion of the investigator,
9. Prothrombin time (international normalized ratio, INR) >1.3,
10. Serum creatinine >175 µmol/L or creatinine clearance <60 mL/min.
11. History of hypersensitivity reaction, anaphylaxis or other CS reactions or known allergy to the study drug or its ingredients including but not limited to dextran.
12. Positive alcohol breath test at Screening, upon admission to the clinic on Day -1.
13. Positive urine drugs of abuse test at Screening, upon admission to the clinic on Day -1.
14. Participant has a positive cotinine test at Screening, upon admission to the clinic on Day -1.
15. Participant is breastfeeding/lactating or pregnant, or planning to breastfeed or become pregnant during the study.
16. Immunosuppressant therapies including methotrexate, azathioprine, or long-tern systemic corticosteroids within 2 months prior to Day 1.
17. Treatment with any other investigational therapy or device within 6 weeks or within 5 half-lives, whichever is longer, prior to Day 1.
18. Known substance abuse or medical, psychological, or social conditions other than PBC or PSC, or prior therapy that in the opinion of the PI would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/10/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/02/2025
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
CMAX Clinical Research - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Parvus Therapeutics, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Avance Clinical Pty Ltd.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Senior Director, Clinical Operations
Address 0 0
Country 0 0
Phone 0 0
+1 949-378-0896
Fax 0 0
Email 0 0
sgrimberg@parvustx.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06798454