PruritusPhase 2NCT06733519
TH104 for the Treatment of Pruritus in Primary Biliary Cholangitis
A Phase 2 study testing Nalmefene in people with Pruritus and Primary Biliary Cholangitis, run by Tharimmune Inc.
Trial summary
A phase 2a, multicenter, randomized, double-blind, placebo-controlled study of TH104 in primary biliary cholangitis (PBC) participants with moderate to severe pruritus. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pruritus, Primary Biliary Cholangitis
- What is being tested?
- Nalmefene
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2026to 1 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Who cannot join
- 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.
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- 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.
- Participation in a clinical trial with an investigational product within 30 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer) before the first dosing in this study.
- Decompensated liver disease (encephalopathy, ascites, or Child Pugh score > 10 points). Participants with compensated cirrhosis will be eligible for enrollment after the DSMB reviewed the safety and tolerability of TH104 for the first 10 non-cirrhotic participants).
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Evaluation of TH104 for Moderate to Severe Pruritus in Primary Biliary Cholangitis: a Double-blind, Randomized, Placebo-controlled, Phase 2a Study
A phase 2a, multicenter, randomized, double-blind, placebo-controlled study of TH104 in primary biliary cholangitis (PBC) participants with moderate to severe pruritus.
Read the detailed description
Following written informed consent, participants with PBC and pruritus will be screened to establish study eligibility. Eligible participants will participate in a one-week observation period for baseline recording, to train participants in the use of electronic PRO tools, and establish baseline itch scores. Another eligibility assessment will be done at the end of this observation period (i.e., at baseline [Day 0]) to ensure that no changes in eligibility have occurred and to confirm that the participant remains eligible. At the baseline visit, participants will be randomized to receive placebo or TH104 treatment. Block randomization will be used, in a 1:2 ratio of placebo:TH104. Treatment will start with a 1-week dose escalation period in which participants will be escalated from 2 mg/day to 4 mg/day TH104 or matching placebo. This will be followed by 2 weeks of treatment with 8 mg and then 3 weeks of 16 mg of TH104 or matching placebo. Following the end of treatment, participants will enter a two-week follow-up period.
- Conditions
- Pruritus, Primary Biliary Cholangitis
- Being tested
- Nalmefene, Placebo
- Medical subject headings
- Pruritus, Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NalmefeneDrug
Th-104 Nalmefene Mucoadhesive Buccal strip
PlaceboDrug
Matching placebo to TH-104
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Not described Receives: Drug: Nalmefene |
| Control | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 42 days
Secondary outcomes (5)
Difference in daily itch score between TH104 and placebo
Measured: 42 days
Change in participants reported outcome for PBC-40 questionnaire
The PBC-40 is a disease specific questionnaire that assess PBC related symptoms . The six domains of PBC-40 relate to fatigue, emotional, social, and cognitive function, general symptoms, and itch
Measured: 42 days
Change in participants reported outcome for 5-D itch questionnaire.
The 5-D itch scale was developed as a brief but multidimensional questionnaire designed to be useful as an outcome measure in clinical trials. The five dimensions are degree, duration, direction, disability and distribution.
Measured: 42 days
Change in participants reported outcome for EQ5D quality of life questionnaire
EQ-5D assesses health status in terms of five dimensions of health.
Measured: 42 days
Change in Fatigue Severity Scale from baseline to the end of treatment.
The FSS questionnaire contains nine statements that rate the severity of fatigue symptoms
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2024
- Study start1 Jun 2026 (estimated)
- Primary completion1 Mar 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PruritusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tharimmune Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06733519
- Sponsor's protocol ID
- TH104-108
- Status last verified
- Dec 2024
- First submitted
- 3 Dec 2024
- Last updated
- 9 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of TH104 for Moderate to Severe Pruritus in Primary Biliary Cholangitis: a Double-blind, Randomized, Placebo-controlled, Phase 2a Study
- ClinicalTrials.gov ID
- NCT06733519
- Acronym / sponsor ID
- TH104-108
- Conditions
- Pruritus, Primary Biliary Cholangitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Tharimmune IncIndustry (pharma, biotech, devices)
- Study start
- 1 Jun 2026 (estimated)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 13 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A phase 2a, multicenter, randomized, double-blind, placebo-controlled study of TH104 in primary biliary cholangitis (PBC) participants with moderate to severe pruritus.
Detailed description
Following written informed consent, participants with PBC and pruritus will be screened to establish study eligibility. Eligible participants will participate in a one-week observation period for baseline recording, to train participants in the use of electronic PRO tools, and establish baseline itch scores. Another eligibility assessment will be done at the end of this observation period (i.e., at baseline [Day 0]) to ensure that no changes in eligibility have occurred and to confirm that the participant remains eligible. At the baseline visit, participants will be randomized to receive placebo or TH104 treatment. Block randomization will be used, in a 1:2 ratio of placebo:TH104. Treatment will start with a 1-week dose escalation period in which participants will be escalated from 2 mg/day to 4 mg/day TH104 or matching placebo. This will be followed by 2 weeks of treatment with 8 mg and then 3 weeks of 16 mg of TH104 or matching placebo. Following the end of treatment, participants will enter a two-week follow-up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Nalmefene |
| Control | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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:
- 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:
Key exclusion criteria (17 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NalmefeneTh-104 Nalmefene Mucoadhesive Buccal strip | Drug | Treatment |
| PlaceboMatching placebo to TH-104 | Drug | Control |
Primary outcome
The primary objective is to investigate the safety and tolerability of repeat doses of TH104
Time frame: 42 days
Percentage of participants with treatment-related adverse events as coded by MedDRA.
5 secondary outcomes
Difference in daily itch score between TH104 and placebo
Time frame: 42 days
Change in participants reported outcome for PBC-40 questionnaire
Time frame: 42 days
Change in participants reported outcome for 5-D itch questionnaire.
Time frame: 42 days
Change in participants reported outcome for EQ5D quality of life questionnaire
Time frame: 42 days
Change in Fatigue Severity Scale from baseline to the end of treatment.
Time frame: 42 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nalmefene in people with Pruritus and Primary Biliary Cholangitis, run by Tharimmune Inc.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Head of Clinical Operations at Tharimmmune Inc (908-955-3140, clinops@tharimmune.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective is to investigate the safety and tolerability of repeat doses of TH104 (time frame: 42 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2025; AzTrials last refreshed its copy on 8 Nov 2026.