HIV Associated Polyneuropathy
Conditions
Keywords
Neuropathy, HIV-DSP
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.
Detailed description
Phase A: Is an open-labeled feasibility investigation of the safety, tolerability, and limited efficacy in 14 subjects with HIV-associated distal sensory polyneuropathy (HIV-DSP) after topical daily dosing of WST-057 (4% pirenzepine free base monohydrate). Subjects will be stratified based on their baseline scores for pain/discomfort using the Visual Analog Scale (VAS). Subjects will attend visits at screening; Day 0 (baseline); Weeks 4, 8, and 16; and follow-up (Week 18). Phase B: Is a randomized outpatient, double-blind, placebo-controlled, single-site study of the safety, tolerability, and exploratory efficacy of topically administered WST-057 for 16 weeks in subjects with HIV-associated distal sensory polyneuropathy (HIV-DSP). Stratification of subjects based on baseline pain will be included based on the results of Part A. Subjects will attend visits at screening; Day 0 (baseline); Weeks 4, 8, and 16; and follow-up (Week 18). Approximately 60 subjects with HIV-DSP will be randomized to 1 of 2 treatment groups in a 3:2 ratio: WST-057 (4 mL) (n = 36 subjects) versus placebo control 4 mL (n = 24 subjects); with the assumption that a total of 50 subjects will complete the study. This study is designed with 4 periods in both study phases: screening, baseline/day 0, outpatient treatment, and safety follow-up.
Interventions
DRUGWST-057
WST-057 topical solution
DRUGPlacebo
WST-057 Matching placebo
Sponsors
WinSanTor, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part A: Open label, Part B: double-blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Patients are eligible for the study if all the following criteria are met: 1. HIV infection documented by serologic testing at screening; virally suppressed on ART. 2. Male and female patients in the age range of 18 to 80 years (inclusive). 3. 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); 4. Baseline IENF density \<5%ile (ankle) based on age- and sex-adjusted Lauria norms. 5. Provide written informed consent prior to entering the study or undergoing any study procedures. 6. 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. 7. 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). 8. 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. 9. 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. 10. 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. 11. Be on stable nonpharmacological pain/uncomfortable sensation treatment for at least 4 weeks prior to screening and remain on this stable treatment throughout the study (unless otherwise directed by a physician). Nonpharmacologic pain treatment includes the following: relaxation/hypnosis, physical or occupational therapy, counseling, etc. Episodic or periodic treatments, such as monthly injections for treatment of pain (e.g., local anesthetics) or trans electrical nerve stimulation will not be permitted. 12. Regular and stable use of pharmacological pain/uncomfortable sensation treatment (less than or equal to 30 mg morphine equivalent) for at least 8 weeks prior to screening. 13. General health status must be acceptable for participation in this 16-week clinical study, during screening per judgment of the Investigator. Any question regarding eligibility will be addressed with the medical monitor. 14. Fluency (oral and written) in the language in which the standardized tests will be administered (English or Spanish)
Exclusion criteria
Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent Adverse Events as assessed by hematology and clinical pathology blood tests | 16 weeks | 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. |
| 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). | 16 weeks | 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. |
| Incidence of Treatment Emergent Adverse Events as assessed by ECG (measuring p wave, QRS complex, QT interval) | 16 weeks | 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. |
| 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 | 16 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient's Global Impression of Change (PGIC) | 16 weeks | The PGIC scale will be used to assess patients' perception of changes following treatment (i.e., feeling better or feeling worse). The PGIC is a 7-point scale from much improved to much worse. The PGIC is commonly used in clinical studies assessing pain relief following treatment, due to its ease of administration and scoring and because it is a generic scale applicable to a wide variety of conditions and treatments including diabetic peripheral neuropathy |
| Quantitative Sensory Testing (QST) | 16 weeks | QST for vibration, warm and cold perception thresholds on both great toes will be assessed. A reduction in QST vibration threshold has shown to have high diagnostic value in subjects with HIV-associated neuropathies. |
| IENFD change from baseline for both treated and untreated skin | 16 weeks | Quantification of IENF density (IENFD) by skin biopsy: This measurement will provide the other co-secondary outcome measures for the study so that effects on both patient function and nerve structure are assessed. IENFD is the gold standard for measuring small fiber neuropathy. |
| Neuropathic Pain Scale-10 (NPS-10) | 16 weeks | The NPS-10 will be used to assess the effect of treatments impacting neuropathic pain. It is reported on 0-10 scale with 0 indicating no pain and 10 indicating the most pain imaginable. It is suggested that an NPS-10 score greater than 43 of 100 may indicate the presence of neuropathic conditions. |
| Utah Early Neuropathy Score (UENS) | 16 weeks | UENS is a simple, rapid, and reproducible test targeted to detect early sensory peripheral neuropathy. It includes motor examination, pin sensation, allodynia, hyperesthesia, large-fiber sensation, and deep tendon reflexes. The sensations are reported on 0-, 1-, or 2-point scoring for normal, reduced or absent vibration or reflexes. |
| Visual Analogues Score (VAS) for pain assessment | 16 weeks | Scores are based on self-reported measures of symptoms that are recorded with a single mark placed at one point along a horizontal line 100 mm in length that represents a continuum between the two ends of the scale-no pain on the left end of the scale and the worst imaginable pain on the right end of the scale. |
| Neuropathy Total Symptom Score-6 (NTSS-6) | 16 weeks | The NTSS-6 is a validated tool that assesses intensity and frequency of different pain modalities (aching, burning, prickling & lancinating pain, numbness and allodynia) in patients with neuropathy. Each sensation is reported on a 4-point scale from Not present to Severe. It shows good internal consistency, test-retest reliability, and construct validity. |
| Medical Outcomes Study HIV Health Survey (MOS-HIV) | 16 weeks | MOS-HIV is a brief, comprehensive health status measure that has been used extensively in studies of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). The 35-item questionnaire includes ten dimensions (health perceptions, pain, physical, role, social and cognitive functioning, mental health, energy, health distress and quality of life (QoL) and takes approximately 5 minutes to complete. Subscales are scored on a 0-100 scale (a higher score indicates better health) and physical and mental health summary scores can be generated. |
Countries
United States
Outcome results
None listed