TH104 for the Treatment of Pruritus in Primary Biliary Cholangitis

NCT06733519 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: TH104-108
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

A phase 2a, multicenter, randomized, double-blind, placebo-controlled study of TH104 in primary biliary cholangitis (PBC) participants with moderate to severe pruritus.

Conditions

Pruritus; Primary Biliary Cholangitis

Outcome Measures

Primary Outcomes (1)

• The primary objective is to investigate the safety and tolerability of repeat doses of TH104

  Percentage of participants with treatment-related adverse events as coded by MedDRA.

  42 days

Secondary Outcomes (5)

• Difference in daily itch score between TH104 and placebo

  42 days

• Change in participants reported outcome for PBC-40 questionnaire

  42 days

• Change in participants reported outcome for 5-D itch questionnaire.

  42 days

• Change in participants reported outcome for EQ5D quality of life questionnaire

  42 days

• Change in Fatigue Severity Scale from baseline to the end of treatment.

  42 days

Study Arms (2)

Treatment

EXPERIMENTAL

Drug: Nalmefene

Control

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Nalmefene DRUG

Th-104 Nalmefene Mucoadhesive Buccal strip

Treatment

Placebo DRUG

Matching placebo to TH-104

Control

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women aged 18 to 75 years, inclusive, at the time of signing the informed consent form.
• Diagnosis of PBC, as demonstrated by the participant presenting with at least 2 of the following criteria at the Screening Visit:
• history of sustained increased alkaline phosphatase (ALP) levels first recognized at least 6 months prior to the Screening Visit
• positive antimitochondrial antibodies (AMA) titer (\>1:40 titer on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay \[ELISA\])
• PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive)
• liver biopsy consistent with PBC Note: Participants with compensated cirrhosis will be eligible for enrollment only after the DSMB reviewed the safety and tolerability of TH104 in the first 10 non-cirrhotic participants.
• Screening ALP value below 10 × upper limit of normal (ULN).
• Participants taking the following drugs may be enrolled to the study, as long as they are on stable doses for \> 12 weeks prior to the Screening Visit; Ursodeoxycholic acid (UDCA) Obeticholic acid Elafibranor Seladelpar Fibrates such as bezafibrate and fenofibrate Cholestyramine Antihistamines
• Symptoms of pruritus - rated as NRS \> 4 for worst daily score:
• At screening AND
• At least on 4 days during the 1-week baseline observation period.
• A woman is eligible to participate if she is not breast-feeding or pregnant, as confirmed by a negative serum human chorionic gonadotrophin (hCG) test or at least one of the following conditions applies:
• Non-reproductive potential defined as pre-menopausal with a documented tubal ligation or hysterectomy; or post-menopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 mIU/mL and estradiol \<40 pg/mL (\<147 pmol/L) is confirmatory\]. Women on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods along with either a second form of highly effective contraception or barrier protection (condoms with spermicide) if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment;
• Reproductive potential and agrees to follow one of the contraception options methods for the specified duration of time.
• For men participating in the study and having a female partner - birth control methods described above will have to be used throughout the study.

You may not qualify if:

• Screening total bilirubin \>2.0 x ULN.
• Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>4 x ULN.
• Screening serum creatinine \>2.5 mg/dL (221 µmol/L).
• History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites).
• History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus (HCV, HBV) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease, definite autoimmune hepatitis or biopsy-proven non-alcoholic steatohepatitis (NASH/MASH/MAFLD).
• Thyroid stimulating hormone (TSH) out of normal ranges.
• Administration of the following drugs at any time during the 3 months prior to the Screening Visit: colchicine, methotrexate, azathioprine, opioids, opioids antagonists, or systemic corticosteroids.
• Current or chronic history of inflammatory bowel disease, chronic diarrhea, Crohn's disease, or diarrhea related to malabsorption syndromes.
• Based on averaged corrected QT interval (QTc) values of triplicate electrocardiograms (ECGs) obtained at least 5 minutes apart: QTc ≥450 msec; or QTc ≥480 msec in participants with Bundle Branch Block.
• History of sensitivity to any of the study medications (or components thereof) or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
• History of regular alcohol consumption within 6 months of the Screening Visit defined as an average weekly intake of \>21 units for men or \>14 units for women. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• A positive screening drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids, and benzodiazepines.
• Where participation in the study would result in blood in blood sampling in excess of 500 mL within a 56-day period.
• Treatment with sertraline and/or rifampicin \< 4 weeks prior to the Screening Visit.
• Clinically significant abnormality of the buccal mucosa which could impact drug absorption.

Sponsors & Collaborators

• Tharimmune Inc: lead

MeSH Terms

Conditions

Pruritus; Liver Cirrhosis, Biliary

Interventions

nalmefene

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes

Central Study Contacts

Head of Clinical Operations at Tharimmmune Inc

CONTACT

908-955-3140; clinops@tharimmune.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2024
• First Posted: December 13, 2024
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: September 9, 2025

Record last verified: 2024-12