Efficacy and Safety of ATTO-1310 in the Treatment of Participants With Chronic Pruritus of Unknown Origin

Phase 2Not Yet RecruitingNCT07833306

Attovia Therapeutics Inc300 enrolled

Overview

The goal of this clinical trial is to assess the efficacy and safety of ATTO-1310 in patients with chronic pruritus/itch of unknown origin. The main questions it aims to answer are: Does ATTO-1310 treatment alleviate symptoms of itch in participants with chronic pruritus/itch? What medical problems do participants have when taking ATTO-1310 for 24 weeks? Researchers will compare ATTO-1310 to a placebo (a look-alike substance that contains no drug). Participants will be dosed with ATTO-1310 or a placebo, visit the clinic for checkups and tests, and keep a diary of their symptoms.

This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of ATTO-1310 in adults with chronic pruritus/itch of unknown origin (CPUO). Participants with CPUO will receive one of three induction treatments (low dose ATTO-1310, high dose ATTO-1310, or placebo) for 12 weeks. Following induction, participants will be assessed for response to treatment. Response to the 12 week induction treatment will determine their treatment progression for the maintenance period. Responders will be re-randomized to one of 4 ATTO-1310 active treatment regimens (high or low dose combined with frequent or infrequent dosing). Non-responders and participants who received placebo during the induction period will be assigned to receive a high dose high frequency ATTO-1310 regimen for the maintenance period through 28 weeks. Participants will be followed for safety through week 36.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

300

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Aged 18 to 90 years with a body weight of 50 to 125 kg and body mass index (BMI) between 18.5 and 40 kg/m\^2. * History of chronic pruritus for at least 6 months that is considered of unknown origin (without a clear association to another condition or medication) as assessed by the Investigator. * Chronic pruritus must affect at least 2 of the following body areas: legs, arms, or trunk. * History of inadequate control of pruritus with at least 1 antihistamine within 6 months of Screening. * Patient Global Impression of Severity (PGI-S) of pruritus of "severe" at Screening. * Use of a stable dose of topical bland emollient twice daily for at least 2 weeks immediately before Day 1 * Weekly mean of daily WI-NRS ≥7 at Day 1 * Negative pregnancy test Exclusion Criteria: * Known condition, other than dry skin, that is considered by the Investigator to be the primary cause of chronic pruritus, including: Presence of a primary dermatologic condition associated with pruritic skin lesions, regional neuropathic pruritus with the exception of peripheral small fiber neuropathy, severe renal failure, hepatobiliary disease, recent infectious dermatoses, suspected somatoform pruritus, ongoing drug-induced pruritus, malignancy or hemopathy, uncontrolled endocrine disease, * Liver function tests (bilirubin, AST, ALT, alkaline phosphatase) \>2.5 times above the upper limit of normal * Estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m² * History of malignancy within 5 years of Screening * History of severe or uncontrolled asthma * History of known primary immunodeficiency, is considered immunocompromised, or has been treated for a parasitic infection in the past 6 months. * History of attempted suicide within the past 2 years. * History of hypersensitivity (including anaphylaxis) to a biologic medication, vaccine, an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody), or to any of the IP excipients * Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or is positive for HIV. * Active or untreated latent tuberculosis (TB) infection. * Any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics, or antifungals within 2 weeks before Day 1. * History of drug or alcohol abuse within 1 year of Screening

Outcomes

Primary Outcomes

≥4-point improvement from baseline in Worst Itch Numerical Rating Scale (WI-NRS) at Week 12 (WI-NRS4 response)

Participants achieved a response if their WI-NRS improved 4 or more points from baseline on a scale ranging from zero (no itch) to 10 (worst possible itch). The baseline is calculated as the average in the final week prior to Day 1. The WI-NRS4 response endpoint at Week 12 is calculated as the average of the daily WI-NRS during Week 12 visit relative to the baseline average WI-NRS.

Time frame: Baseline and Week 12

Secondary Outcomes

WI-NRS4 response at Week 4

Participants achieved a response if they had an improvement of at least 4 points on a scale ranging from 0 (no itch) to 10 (worst possible itch).

Time frame: Baseline and Week 4

≥5-point improvement from baseline in WI-NRS (WI-NRS5 response) at Week 4

Participants achieved a response if they scored a 5 or more point improvement from baseline on a scale ranging from 0 (no itch) to 10 (worst possible itch).

Time frame: Baseline and Week 4

≥5-point improvement from baseline in WI-NRS (WI-NRS5 response) at Week 12

Participants achieved a response if they scored a 5 or more point improvement from baseline on a scale ranging from 0 (no itch) to 10 (worst possible itch).

Time frame: Baseline and Week 12

WI-NRS <2 (WI-NRS<2 response) at Week 4

Participants achieved a response if their WI-NRS score was less than 2 at Week 4

Time frame: Week 4

WI-NRS <2 (WI-NRS<2 response) at Week 12

Participants achieved a response if their WI-NRS score was less than 2 at Week 4

Time frame: Week 12

Patient Global Impression of Severity (PGI-S) of pruritus of "none" or "mild" at Week 4

Participant's impression of severity of itching over the past 7 days on a 4-point Likert scale with the options of: none, mild, moderate, or severe.

Time frame: Week 4

Patient Global Impression of Severity (PGI-S) of pruritus of "none" or "mild" at Week 12

Participant's impression of severity of itching over the past 7 days on a 4-point Likert scale with the options of: none, mild, moderate, or severe.

Time frame: Week 12

Absolute change from baseline in weekly average WI-NRS at Week 4

WI-NRS score of zero is equivalent to "no itch" and 10 is equivalent to "worst possible itch". Positive change from baseline will indicate worsening of itch. Negative change from baseline will indicate improvement. No change from baseline will indicate no improvement.

Time frame: Baseline, Week 4

Absolute change from baseline in weekly average WI-NRS at Week 12

Time frame: Baseline, Week 12

Percent change from baseline in weekly average WI-NRS at Week 4

WI-NRS score of zero is equivalent to "no itch" and 10 is equivalent to "worst possible itch". Positive percent change from baseline will indicate worsening of itch. Negative Percent change from baseline will indicate improvement. No change from baseline will indicate no improvement.

Time frame: Baseline, Week 4

Percent change from baseline in weekly average WI-NRS at Week 12

Time frame: Baseline, Week1 12

Absolute change from baseline in weekly average itch-related sleep disruption NRS (iSD-NRS) at Week 4

iSD-NRS score of 0 is equivalent to "itching did not disrupt my sleep" and 10 indicates "complete disruption, I was unable to sleep because of itching." Positive change from baseline will indicate worsening of sleep disruption due to itch. Negative change from baseline will indicate improvement. No change from baseline will indicate no improvement.

Time frame: Baseline, Week 4

Absolute change from baseline in weekly average itch-related sleep disruption NRS (iSD-NRS) at Week 12

Time frame: Baseline, Week 12

Percent change from baseline in weekly average iSD-NRS at Week 4

iSD-NRS score of 0 is equivalent to "itching did not disrupt my sleep" and 10 indicates "complete disruption, I was unable to sleep because of itching." Positive percent change from baseline will indicate worsening of itch. Negative percent change from baseline will indicate improvement. No change from baseline will indicate no improvement.

Time frame: Baseline, Week 4

Percent change from baseline in weekly average iSD-NRS at Week 12

Time frame: Baseline, Week 12

WI-NRS4 response through Week 28

Participants achieved a response if they had a 4 or more point improvement in WI-NRS on a scale where zero is "no itch" and 10 is equivalent to "worst possible itch".

Time frame: Weekly through Week 28

Absolute change from baseline in weekly average WI-NRS through Week 28

Time frame: Baseline and weekly through week 28

Percent change from baseline in weekly average WI-NRS through Week 28

Time frame: Baseline and weekly through Week 28

Incidence and severity of treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) from baseline through end of study (EOS)

The analysis will describe the incidence of AEs and laboratory abnormalities from baseline through end of study. AEs will be coded according to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA). Their severity will be graded using the NCI CTCAE V6.0 or current version.

Time frame: Baseline through Day 253 (EOS)

Efficacy and Safety of ATTO-1310 in the Treatment of Participants With Chronic Pruritus of Unknown Origin

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts