Melanoma
Conditions
Brief summary
To evaluate the safety and tolerability of intradermal injections of IMM-101 (Heat-killed Mycobacterium obuense) in melanoma cancer patients.
Detailed description
The proposed study is a first-in-man, placebo-controlled, dose escalation trial to evaluate the safety and tolerability of three different doses of IMM-101 administered intradermally to melanoma patients. Additionally, the study aims to characterize local responses to this vaccine in order to delineate unexpected / unacceptable local reactions from those indicative of appropriate immunological response in this patient group.
Interventions
BIOLOGICALHeat killed whole cell M. obuense (IMM-101) 0.1 mg
Each patient will receive an intradermal placebo injection of borate buffered saline solution (day -3) to provide an intra patient placebo control. Patients who were willing and able to proceed with the study will receive an intradermal injection of a single dose level of IMM 101 on three subsequent occasions. Doses of IMM 101 were administered over a 4 week period on days 0, 14 and 28. Dose levels to be administered are 0.1 mg, 0.5 mg and 1.0 mg.
BIOLOGICALHeat-killed whole cell M.obuense (IMM-101) 0.5 mg
Each patient will receive an intradermal placebo injection of borate buffered saline solution (day -3) to provide an intra patient placebo control. Patients who were willing and able to proceed with the study will receive an intradermal injection of a single dose level of IMM 101 on three subsequent occasions. Doses of IMM 101 were administered over a 4 week period on days 0, 14 and 28.
BIOLOGICALHeat killed whole cell M.obuense (IMM-101) 1.0 mg
Each patient will receive an intradermal placebo injection of borate buffered saline solution (day -3) to provide an intra patient placebo control. Patients who were willing and able to proceed with the study will receive an intradermal injection of a single dose level of IMM 101 on three subsequent occasions. Doses of IMM 101 were administered over a 4 week period on days 0, 14 and 28.
Sponsors
HCA International Limited
Theradex
Immodulon Therapeutics Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* confirmed diagnosis of disease free stage III or stage IV melanoma (with or without metastases) or stable disease (if with metastases) and receiving no other treatment * willing to use effective contraception for the duration of the study * able to comply with the requirement to complete a diary card
Exclusion criteria
* Pregnant or lactating females * Major surgery within the 14 days preceding the screening visit * Suspicion of a previous infection with mycobacteria including previous tuberculosis (TB) prophylaxis * Treatment with another investigational medicinal product within the last 30 days prior to the screening visit * Previous treatment with M. vaccae * Exposure to Bacille Calmette Guérin vaccine (BCG) within the last 12 months * Concurrent uses of drugs likely to reduce inflammation at the local injection site or dampen/modulate the immune system * Depot injection of corticosteroids within 6 weeks of the screening visit or chronic systemic corticosteroids in the 2 weeks prior to the screening visit * Ongoing treatment with radiotherapy, cytotoxic chemotherapy or chemotherapy in the last 30 days prior to the screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 56 days | Safety and tolerability were measured with respect to: 1. Safety measurements 2. Local tolerability at the site of intradermal injection 3. Incidence of adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Administration Site Reactions | Day -3 to Day 56 | Local skin reactions are viewed as a normal and predicted reaction to exposure to a preparation of mycobacterial antigens. All patients experienced administration site reactions and all reactions were examined and characterised. However only those reported as adverse events are presented here. |
Countries
United Kingdom
Participant flow
Recruitment details
A total of 24 patients with melanoma entered the screening phase of this study between 10 March 2010 and 27 July 2010.
Pre-assignment details
Five patients were found to be ineligible and failed screening. These patients were withdrawn before receiving study medication.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 IMM-101 0.1 mg | 6 |
| Group 2 IMM-101 0.5 mg | 7 |
| Group 3 IMM-101 1.0 mg | 6 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Group 2 | Group 3 | Group 1 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 1 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 5 Participants | 11 Participants |
| Age Continuous | 56.1 years STANDARD_DEVIATION 20.2 | 56.3 years STANDARD_DEVIATION 18.8 | 47.3 years STANDARD_DEVIATION 17.3 | 53.4 years STANDARD_DEVIATION 18.3 |
| Region of Enrollment United Kingdom | 7 participants | 6 participants | 6 participants | 19 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 6 | 7 / 7 | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 | 1 / 7 | 0 / 6 |
Outcome results
Primary
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Safety and tolerability were measured with respect to: 1. Safety measurements 2. Local tolerability at the site of intradermal injection 3. Incidence of adverse events.
Time frame: 56 days
Population: All analyses were based on the safety population, which comprised of all patients who received at least one dose of IMP. Safety measurements and nature and incidence of adverse events were reported for the Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMM-101 0.1 mg | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 6 Participants |
| IMM-101 0.5 mg | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 7 Participants |
| IMM-101 1.0 mg | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 6 Participants |
Secondary
Administration Site Reactions
Local skin reactions are viewed as a normal and predicted reaction to exposure to a preparation of mycobacterial antigens. All patients experienced administration site reactions and all reactions were examined and characterised. However only those reported as adverse events are presented here.
Time frame: Day -3 to Day 56
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMM-101 0.1 mg | Administration Site Reactions | 1 Participants |
| IMM-101 0.5 mg | Administration Site Reactions | 3 Participants |
| IMM-101 1.0 mg | Administration Site Reactions | 5 Participants |