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
Overview
- Phase
- Phase 1
- Intervention
- UTTR1147A
- Conditions
- Neuropathic Diabetic Foot Ulcers
- Sponsor
- Genentech, Inc.
- Enrollment
- 72
- Locations
- 32
- Primary Endpoint
- Percentage of Participants with Adverse Events
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Cohort A - UTTR1147A, 0.8-6.0 cm^2, No Infection - Dose 1
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).
Intervention: UTTR1147A
Cohort B - UTTR1147A, 0.8-6.0 cm^2, No Infection - Dose 2
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).
Intervention: UTTR1147A
Cohort C - UTTR1147A, 0.8-6.0 cm^2, Mild Infection - Dose 2
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).
Intervention: UTTR1147A
Cohort D - UTTR1147A, 1.5-6.0 cm^2, Mild Infection - Dose 2
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).
Intervention: UTTR1147A
Cohort E - UTTR1147A, 0.8-6.0 cm^2, No infection - Dose 3
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).
Intervention: UTTR1147A
Placebo
Participants will receive UTTR1147A matching placebo SC in each cohort for 12 weeks (a total of 4 doses).
Intervention: Placebo
Outcomes
Primary Outcomes
Percentage of Participants with Adverse Events
Time Frame: Baseline up to Day 141
Secondary Outcomes
- 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))