A 16-Week Study of Pirenzepine or Placebo to Treat HIV-Associated Distal Sensory Polyneuropathy in Patients With HIV

NCT05005078 | Completed Phase 2 FDA Drug

• 1 other identifier: WST-PZP-004
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

This is a two-part study of the safety, tolerability, and efficacy of topically administered WST-057 for 16 weeks in subjects with HIV with sensory polyneuropathy.

Conditions

HIV Associated Polyneuropathy

Keywords

Neuropathy; HIV-DSP

Outcome Measures

Primary Outcomes (4)

• Incidence of Treatment Emergent Adverse Events as assessed by hematology and clinical pathology blood tests

  Safety will be assessed by observing changes in patients' blood tests when compared to normal lab values/ranges after once daily dosing of 1 dose level of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAEv4.0 will be reported.

  16 weeks

• Incidence of Treatment Emergent Adverse Events as assessed by vital signs (blood pressure (diastolic and systolic mmHg), heart rate (beats per minute), respiratory rate (breaths per minute).

  Safety will be assessed by observing changes in patients' blood tests when compared to normal lab values/ranges after once daily dosing of 1 dose level of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAEv4.0 will be reported.

  16 weeks

• Incidence of Treatment Emergent Adverse Events as assessed by ECG (measuring p wave, QRS complex, QT interval)

  Safety will be assessed by observing changes in patients' blood tests when compared to normal lab values/ranges after once daily dosing of 1 dose level of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAEv4.0 will be reported.

  16 weeks

• Incidence of Treatment Emergent Adverse Events as assessed by dermal assessment (Draize score 0.0-4.0) score of skin erythema, edema pruritus and dryness score) of the dosing area

  Safety will be assessed by observing changes in patients' blood tests when compared to normal lab values/ranges after once daily dosing of 1 dose level of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAEv4.0 will be reported.

  16 weeks

Secondary Outcomes (8)

• IENFD change from baseline for both treated and untreated skin

  16 weeks

• Visual Analogues Score (VAS) for pain assessment

  16 weeks

• Neuropathy Total Symptom Score-6 (NTSS-6)

  16 weeks

• Medical Outcomes Study HIV Health Survey (MOS-HIV)

  16 weeks

• Patient's Global Impression of Change (PGIC)

  16 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

WST-057 Matching placebo

Drug: Placebo

WST-057

EXPERIMENTAL

WST-057 topical solution

Drug: WST-057

Interventions

WST-057 DRUG

WST-057 topical solution

WST-057

Placebo DRUG

WST-057 Matching placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are eligible for the study if all the following criteria are met:
• HIV infection documented by serologic testing at screening; virally suppressed on ART.
• Male and female patients in the age range of 18 to 80 years (inclusive).
• Diagnosis of HIV-DSP determined by a neurological exam performed by qualified personnel and defined as one or more clinical signs (symmetrical, diminished distal vibration or dull/sharp sensation in feet or reduced ankle reflexes using HNRC CH40);
• Baseline IENF density \<5%ile (ankle) based on age- and sex-adjusted Lauria norms.
• Provide written informed consent prior to entering the study or undergoing any study procedures.
• Females should be either not of childbearing potential as a result of surgery or menopause (1 year after onset), or of childbearing potential and must be practicing a highly effective medically acceptable method of contraception, including abstinence; hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device or intrauterine system; or vasectomy (partner), for at least 1 month before the screening visit and for 1 month after the end of the last dose of study drug. If access or use of a highly effective medically acceptable method of contraception is not achievable, then a combination of barrier methods (e.g., male condom, female condom, cervical cap, diaphragm, contraceptive sponge) is acceptable. Eligible female subjects must also have a negative serum beta-human chorionic gonadotropin at the screening visit.
• Males must use an acceptable form of contraception (e.g., male condom with diaphragm, male condom with cervical cap, or male condom in association with spermicide).
• If diabetic, glycemic control has been optimized and has been stable for at least three months prior to randomization. Optimal glycemic control (by HgbA1C\<7; at discretion of PI) refers to the best possible diabetic control that an individual patient can attain with usual standards of care, which usually takes more than two months to establish.
• Participating subjects must be reliable, willing, and able to cooperate with all study procedures, including the following:
• Return for study visits on the required dates
• Be physically able to inspect calves, tops of ankles, and soles of feet for wounds, infections, or other anomalies, and be able to self-administer the investigational drug to calves and top surface of feet.
• Be able to accurately and reliably report symptoms (including treatment-emergent signs and symptoms).
• Take study drug as required by protocol.
• If diabetic, be on stable antidiabetic treatment (\> 2 months prior to screening) (oral or injectable antidiabetic therapy and/or lifestyle) that is not anticipated to change during the course of the study, except if medically required.

You may not qualify if:

• Current intoxication (BAC \> 0.08%) at the screening visit at the discretion of the investigator (breathalyzer analysis).
• Neuropathy due to exposure to current use/ chemotherapeutic agents or other neurotoxins; at the discretion of the investigator.
• Individuals with the onset of Type 2 diabetes mellitus before HIV infection.
• Uncontrolled or Insulin-dependent diabetes mellitus.
• Proliferative retinopathy or maculopathy requiring acute treatment.
• Requiring dialysis. Impaired liver function, defined as aspartate aminotransferase or alanineaminotransferase \> 3 times the upper limit of normal.
• Presence of clinically significant peripheral or autonomic neuropathy that is clearly of non HIVN origin.
• Active and/or systemic infections with hepatitis C (as per investigator judgement following serology results) or syphilis, or a history of severe infection during the 30 days prior to screening.
• Diagnosis and/or treatment of malignancy (except for basal cell or squamous cell skin cancer, in-situ carcinoma of the cervix, or in-situ prostate cancer) within the past 5 years.
• Clinically significant diagnosed gastric emptying abnormality (e.g., severe gastroparesis).
• Clinically significant - urinary retention confirmed by bladder ultrasound regardless of etiology.
• Uncontrolled glaucoma.
• Other clinically significant, active (over the past 12 months) disease of the cardiovascular, gastrointestinal, pulmonary, neurological, genitourinary, endocrine, rheumatologic or hematological system that, in the opinion of the Investigator, would compromise the subject's participation in the study, might confound the results of the study, or pose additional risk in administering the study drug.unstable/untreated clinically significant.
• New treatment with (\< 2 months) antioxidant supplements, vitamins, or drugs known to affect oxidative stress and such as Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine and Vitamin B12.
• Mental incapacity, unwillingness, or language barrier precluding adequate understanding of or cooperation with the study.

Sponsors & Collaborators

• WinSanTor, Inc: lead

Study Sites (2)

Palmtree Clinical Research

Palm Springs, California, 92262, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

Study Officials

• Angela Hansen

  WinSanTor, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part A: Open label, Part B: double-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2021
• First Posted: August 13, 2021
• Study Start: February 24, 2022
• Primary Completion: January 18, 2023
• Study Completion: January 24, 2023
• Last Updated: December 4, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)