Safety and Efficacy of ALD518 for Reducing Oral Mucositis in Head and Neck Cancer Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of ALD518 in modifying the course of oral mucositis in subjects with head and neck cancer receiving concomitant chemotherapy and radiotherapy

Detailed Description
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This was a Phase 2, placebo-controlled, double-blind study in subjects newly diagnosed with head and neck cancer (who had not received previous treatment for oral mucositis) and who were receiving concomitant chemotherapy and radiotherapy. Subject eligibility, including tumor staging, was assessed during the screening period, which was to occur within 30 days prior to the initiation of radiation therapy. The radiation therapy treatment period was approximately 7 weeks, depending on the subject's prescribed radiation plan. Prior to the randomized portion of the trial, the first 7 subjects enrolled in the study entered a safety run-in evaluation and received a total of 2 doses of open-label clazakizumab 160 mg IV, 4 weeks apart (Day 0 and Week 4 of radiation); these subjects were not eligible for the randomized portion of the study. Subsequent to completion of the safety run-in, eligible subjects were randomized 1:1:1 to treatment with 2 doses of clazakizumab 160 mg, or clazakizumab 320 mg, or placebo, administered IV 3 weeks apart (Day 0 and Week 3 of radiation therapy). All subjects were to be followed for 4 weeks post last day of radiotherapy treatment for the primary efficacy and safety assessments and then for up to an additional 12 months of long-term follow-up.

Official Title
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A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of ALD518 in the Reduction of Oral Mucositis in Subjects With Head and Neck Cancer Receiving Concomitant Chemotherapy and Radiotherapy

Conditions
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Oral Mucositis

Intervention / Treatment
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* Biological: ALD518
* Drug: 0.9% saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have recently diagnosed (< than 6 months prior to screening visit date), pathologically confirmed, non-metastatic SCC of the oral cavity, oropharynx, hypopharynx or larynx that will be treated with CRT as first-line treatment; subjects with a history of surgical management (approximately 4-6 weeks before RT with sufficient time for post-surgical healing) are eligible Have a plan to receive a continuous course of conventional external beam irradiation delivered by intensity-modulated radiotherapy (IMRT) as single daily fractions of 2.0 to 2.2 Gy, with a cumulative radiation dose between 55 and 72 Gy. Have a plan to receive a standard cisplatin CT regimen administered tri-weekly (80 to 100 mg/m2, on Days 0, 21, and 42) or weekly (30 to 40 mg/m2) or a standard carboplatin regimen administered weekly (100 mg/m2) Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 CRP < 80 mg/L Have adequate hematopoietic, hepatic, and renal function at the screening visit Exclusion Criteria: Tumor of the lips, sinuses, salivary glands, nasopharynx or unknown primary tumor Metastatic disease (M1) Stage IV C Any prior history of head and neck cancer Prior radiation to the head and neck Have had a major surgical procedure, other than for HNC, or significant traumatic injury within 4 weeks prior to the initiation of RT; or anticipation of need for a major surgical procedure during the clinical trial Active infectious disease, excluding oral candidiasis Have OM at the screening visit Have a history of hypersensitivity to monoclonal antibody

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label ALD518<br> | Biological: ALD518<br>* IV<br>|
| Experimental: ALD518 Dose 1<br> | Biological: ALD518<br>* IV<br>|
| Experimental: ALD518 Dose 2<br> | Biological: ALD518<br>* IV<br>|
| Placebo Comparator: Placebo<br> | Drug: 0.9% saline<br>* IV Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities |  | Up to 15 months | 
| Number of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities |  | Up to 15 months | 
| Percent of Participants With All Grades of Oral Mucositis (OM) at a Radiation Dose of 55 Gy | Gray (Gy) is used as a unit of the radiation quantity absorbed dose that measures the energy deposited by ionizing radiation in a unit mass of matter being irradiated, and is used for measuring the delivered dose of ionizing radiation in applications such as radiotherapy. The 55 Gy ulcerative OM assessment is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in their cumulative dose of radiation being ≥ 55 Gy | Up to 12 weeks | 
| Number of Participants With All Grades of OM at a Radiation Dose of 55 Gy | The 55 Gy ulcerative OM assessment is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in their cumulative dose of radiation being ≥ 55 Gy | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy) | The ulcerative OM assessment at a specific cumulative radiation dose (35 Gy, 45 Gy, 55 Gy or 65 Gy) is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in the specific cumulative dose of radiation being ≥35 Gy, ≥45 Gy, ≥55 Gy or≥ 65 Gy | Up to 12 weeks | 
| Number of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy) | The ulcerative OM assessment at a specific cumulative radiation dose (35 Gy, 45 Gy, 55 Gy or 65 Gy) is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in the specific cumulative dose of radiation being ≥35 Gy, ≥45 Gy, ≥55 Gy or≥ 65 Gy | Up to 12 weeks | 
| Percent of Participants With Severe OM at Varying Cumulative Radiation Doses (Gy) | The severe OM assessment at a specific cumulative radiation dose (35 Gy, 45 Gy, 55 Gy or 65 Gy) is defined as the first severe OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in the specific cumulative dose of radiation being ≥35 Gy, ≥45 Gy, ≥55 Gy or≥ 65 Gy | Measured from onset of OM through Week 12 | 
| Number of Participants With Severe OM at Varying Cumulative Radiation Doses (Gy) | The severe OM assessment at a specific cumulative radiation dose (35 Gy, 45 Gy, 55 Gy or 65 Gy) is defined as the first severe OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in the specific cumulative dose of radiation being ≥35 Gy, ≥45 Gy, ≥55 Gy or≥ 65 Gy | Up to 12 weeks | 
| Duration of Ulcerative and Severe OM |  | Up to 12 weeks | 
| Time to Onset of Ulcerative and Severe OM |  | Up to 12 weeks | 
| ALD518 Plasma Concentration at Varying Weeks |  | Baseline and up to 12 weeks | 
| Oral Mucositis Daily Questionnaire (OMDQ) Overall Health Score at Varying Cumulative Radiation Doses (Gy) | Scored on a scale from 0 (worst possible overall health) to 10 (perfect overall health). Higher scores represent better overall health. | Baseline and up to 12 weeks | 
| Functional Assessment of Cancer Therapy - Head and Neck (FACT-HN) Questionnaire Overall Assessment Score at Varying Cumulative Radiation Doses (Gy) | The FACT-HN consists of 28 general + 11 head and neck specific items, each rated on a 0 (not at all) to 4 (very much) Likert type scale. The total score ranges from 0 to 148. Higher scores represent better quality of life. | Baseline and up to 12 weeks | 
| Functional Assessment of Chronic Illness Therapy - Fatigue Questionnaire (FACIT-F) Score at Varying Cumulative Radiation Doses (Gy) | The responses to the 13 items on the FACIT-F questionnaire are each measured on a 5-point Likert scale from 0 (not at all fatigued) to 4 (very much fatigued). The total score ranges from 0 to 52. Higher scores represent less fatigue. | Baseline and up to 12 weeks | 
| Mean Change From Baseline in C-reactive Protein (CRP) Values at Varying Weeks | The level of C-reactive protein (CRP), which can be measured in your blood, increases when there's inflammation in your body. | Baseline and up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral mucositis; head and neck cancer; chemotherapy; radiotherapy