The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of UTTR1147A in Participants With Neuropathic Non-Healing Diabetic Foot Ulcers

Study Overview
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Brief Summary
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This trial will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of repeat dosing of UTTR1147A in participants with neuropathic diabetic foot ulcers that do not respond adequately to standard wound care. Participants across multiple sites will be assigned to one of five cohorts (Cohort A, B, C, D, and E) based on the eligibility criteria and randomized to receive subcutaneous (SC) injections of either UTTR1147A or placebo over 12 weeks in addition to standard wound care.

Official Title
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A Phase Ib, Blinded, Randomized, Multicenter, Multiple-Ascending-Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of UTTR1147A Administered by Subcutaneous Injection in Patients With Non-Healing Neuropathic Diabetic Foot Ulcers

Conditions
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Neuropathic Diabetic Foot Ulcers

Intervention / Treatment
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* Drug: Placebo
* Drug: UTTR1147A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of Type 1 or Type 2 diabetes and confirmed peripheral neuropathy Have adequate circulation to the foot Have an ulcer area at screening up to 6 cm^2 Up to date on all age-appropriate cancer screenings per local standards Exclusion Criteria: Have current evidence of osteomyelitis, cellulitis, or evidence of systemic infection Have gangrene present on any part of the affected foot Known peripheral arterial disease requiring revascularization Have a glycated hemoglobin A1C level of greater than (>) 15% assessed at screening Are receiving oral or parenteral corticosteroids, immunosuppressive, or cytotoxic agents Have active malignancy or any history of a malignancy Use of oral antibiotics at the time of randomization for any reason in participants to be enrolled in Cohorts A, B, E, and any additional uninfected patient cohorts

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A - UTTR1147A, 0.8-6.0 cm^2, No Infection - Dose 1<br>Participants with 0.8-6.0 centimeters square (cm^2) index ulcer area at screening and no infection in index ulcer will receive UTTR1147A SC at Dose Level 1 for 12 weeks (a total of 4 doses). | Drug: UTTR1147A<br>* UTTR1147A will be administered SC.<br>* Other names: RO7021610;|
| Experimental: Cohort B - UTTR1147A, 0.8-6.0 cm^2, No Infection - Dose 2<br>Participants with 0.8-6.0 cm^2 index ulcer area at screening and no infection in index ulcer will receive UTTR1147A SC at Dose Level 2 for 12 weeks (a total of 4 doses). | Drug: UTTR1147A<br>* UTTR1147A will be administered SC.<br>* Other names: RO7021610;|
| Experimental: Cohort C - UTTR1147A, 0.8-6.0 cm^2, Mild Infection - Dose 2<br>Participants with 0.8-6.0 cm^2 index ulcer area at screening and mild infection in index ulcer will receive UTTR1147A SC at Dose Level 2 for 12 weeks (a total of 4 doses). | Drug: UTTR1147A<br>* UTTR1147A will be administered SC.<br>* Other names: RO7021610;|
| Experimental: Cohort D - UTTR1147A, 1.5-6.0 cm^2, Mild Infection - Dose 2<br>Participants with 1.5-6.0 cm^2 index ulcer area at screening and mild infection in index ulcer will receive UTTR1147A SC at Dose Level 2 for 12 weeks (a total of 4 doses). | Drug: UTTR1147A<br>* UTTR1147A will be administered SC.<br>* Other names: RO7021610;|
| Experimental: Cohort E - UTTR1147A, 0.8-6.0 cm^2, No infection - Dose 3<br>Participants with 0.8-6.0 cm^2 index ulcer area at screening and mild infection in index ulcer will receive UTTR1147A SC at Dose Level 3 for 12 weeks (a total of 4 doses). | Drug: UTTR1147A<br>* UTTR1147A will be administered SC.<br>* Other names: RO7021610;|
| Placebo Comparator: Placebo<br>Participants will receive UTTR1147A matching placebo SC in each cohort for 12 weeks (a total of 4 doses). | Drug: Placebo<br>* UTTR1147A matching placebo will be administered SC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events |  | Baseline up to Day 141 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Index Ulcer Surface Area at Weeks 6 and 12 |  | Baseline, Weeks 6 and 12 | 
| Percentage of Participants with Anti-Therapeutic (Anti-UTTR1147A) Antibodies |  | Day 1, 22, 64, 85, 99, early termination visit (up to Day 141) | 
| Serum Concentration of UTTR1147A |  | Pre-dose (0 h) on Days 1, 22, 43, and 64, on Days 4, 8, 71, 85, and 99, early termination (up to Day 141) |