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HAL-MRE1 Subcutaneous Immunotherapy in Ragweed Allergic Patients First-in-human

Primary Purpose

Rhinitis, Allergic, Rhinoconjunctivitis, Allergic

Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
HAL-MRE1
Sponsored by
HAL Allergy
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rhinitis, Allergic focused on measuring Subcutaneous immunotherapy, Ragweed pollen, Allergic rhinitis/rhinoconjunctivitis, Safety, Tolerability

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Signed informed consent.
  2. Male or female subjects aged ≥18 and ≤65 years.
  3. Documented diagnosis of allergic rhinitis/rhinoconjunctivitis (ARC) to ragweed pollen. A documented diagnosis is a documented medical history of ARC symptoms that required treatment after ragweed pollen exposure. Subjects experienced allergy symptoms that required treatment during the previous 2 ragweed seasons, with or without concomitant asthma (asthma must be controlled).
  4. Positive nasal provocation test for ragweed pollen at screening or within the last 6 months.
  5. Positive skin prick test to ragweed allergen at screening or within the last 6 months.
  6. Positive serum specific IgE test for ragweed allergen (IgE level ≥0.7 U/mL).
  7. Forced expiratory volume >70 % or peak expiratory flow >80 % of predicted value.
  8. For asthmatic subjects: asthma control test (ACT) score ≥20.
  9. Subjects are capable and willing to maintain a log of adverse events and concomitant medication throughout the study, as well as to complete a diary 24 hours post investigational medical product injection.
  10. Negative pregnancy test at screening for females of childbearing potential.
  11. Females of childbearing age must be using an effective method of contraception to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of participation in the study. Contraceptive measures considered adequate are:

    1. hormonal contraceptives such as contraceptive pills, transdermal patches, intrauterine devices, intrauterine system implants, or vaginal rings (started at least 4 weeks prior to investigational medical product administration).
    2. double barrier methods e.g. condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent.
    3. sterilization (male or female).
    4. participants who are postmenopausal (12 consecutive months without a period) for at least 2 years.
    5. sexual abstinence or having no sexual relationship with a man.

Exclusion Criteria:

  1. History of anaphylaxis with cardio respiratory symptoms (food allergy, venom allergy, drugs or/and idiopathic reaction).
  2. Alcohol, drug or medication abuse in the past.
  3. Any clinically significant abnormal laboratory parameter at screening as per investigator's discretion.
  4. Clinically relevant sensitization to other allergens if clinical symptoms are expected during the study.
  5. Uncontrolled asthma.
  6. Participation in a clinical interventional study within the last 3 months (e.g. new investigational drug or biological), or plans to participate in another clinical trial during this study, or participation in an observational study (e.g. post marketing study) within the last 30 days unless the observational study aimed to investigate the intradermal test.
  7. Subjects who received immunotherapy for any specific allergen 3 years prior to screening or during the study period.
  8. Subjects who were ever treated with any ragweed allergen specific immunotherapy.
  9. Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs.
  10. Subjects undergoing any immunosuppressive treatment (including anti-IgE therapy) within the last 6 months prior to inclusion in the study as well as during the study.
  11. Active malignancies or any malignant disease during the 5 years prior to screening.
  12. Severe uncontrolled diseases that, in the opinion of the investigator, could increase the risk for subjects participating in the study, including but not limited to: any severe or unstable lung diseases; endocrine diseases; clinically significant renal or hepatic diseases, or hematological disorders; or severe ongoing symptomatic allergic diseases.
  13. Active or acute inflammation or infection of the target organs (nose, eyes) at screening.
  14. Diseases with a contra-indication for the use of adrenaline (e.g. hyperthyroidism, glaucoma).
  15. Lactation.
  16. Severe psychiatric, psychological, or neurological disorders.
  17. Subjects who have any direct working relationship with the (sub-) investigator or study site personnel or are first degree relatives or partners of the investigator or study site personnel or are employees of the sponsor.
  18. Known allergy or hypersensitivity to an excipient in the study drug or placebo.
  19. Subjects receiving the prohibited previous and concomitant medication.

Sites / Locations

  • Inflamax Research Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

HAL-MRE1 0 AUeq

HAL-MRE1 5,000 AUeq

HAL-MRE1 10,000 AUeq

HAL-MRE1 20,000 AUeq

Arm Description

15 subjects will receive placebo. Subjects will receive 7-9 incremental weekly injections. All doses will be subcutaneously injected in a double-blind fashion in the upper arm.

10 subjects will receive HAL-MRE1 5,000 AUeq. Subjects will receive 6-8 incremental weekly injections until reaching the maximum dose of 5,000 AUeq. Subsequently, 1 repeated maximum dose injection will be given 1 week later (total treatment period will be approximately 7-9 weeks). All doses will be subcutaneously injected in a double-blind fashion in the upper arm.

10 patients will receive HAL-MRE1 10,000 AUeq. Subjects will receive 6-8 incremental weekly injections until reaching the maximum dose of 10,000 AUeq. Subsequently, 1 repeated maximum dose injection will be given 1 week later (total treatment period will be approximately 7-9 weeks). All doses will be subcutaneously injected in a double-blind fashion in the upper arm.

10 patients will receive HAL-MRE1 20,000 AUeq. Subjects will receive 6-8 incremental weekly injections until reaching the maximum dose of 20,000 AUeq. Subsequently, 1 repeated maximum dose injection will be given 1 week later (total treatment period will be approximately 7-9 year). All doses will be subcutaneously injected in a double-blind fashion in the upper arm.

Outcomes

Primary Outcome Measures

Occurence of local and systemic reactions
Number, intensity and seriousness of early (within 30 mins from injection), delayed (within 30mins and 3 hours from injection) and late (from 3 hours to 24 hours after injection) local reactions (>8 cm wheal size swelling at injection site) as well as early, delayed and late systemic reactions.

Secondary Outcome Measures

Occurence of other local reactions
Number, intensity and seriousness of other local reactions like itching, pain and redness at injection site.
Occurrence of treatment emergent adverse events
Treatment emergent adverse events will be collected by reporting of adverse events and by clinical relevant changes in e.g. laboratory values, vital signs, physical exam, and lung function in plasma and urine
Number of subjects that reach maximum dose
The number of subjects in each cohort who reach the maximum dose is indicative of HAL-MRE1 tolerability.
Number of injections to reach maintenance dose
The number of injections that subjects in each cohort need to reach the maximum dose will provide an indication of HAL-MRE1 tolerability.
Immunoglobulin Levels
Short term pharmacodynamic effects of HAL-MRE1 will be measured by determining the change in serum levels of allergen specific immunoglobulins (IgE, IgG and IgG4) pre- and post-study treatment in the HAL-MRE versus placebo treated groups.
Change in wheal size after skin prick test
Exploratory efficacy data will be obtained by measuring the change in wheal size following skin prick test with ragweed extract pre- and post-treatment in the HAL-MRE1 versus placebo treated groups.

Full Information

First Posted
November 7, 2018
Last Updated
August 5, 2019
Sponsor
HAL Allergy
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1. Study Identification

Unique Protocol Identification Number
NCT03758456
Brief Title
HAL-MRE1 Subcutaneous Immunotherapy in Ragweed Allergic Patients First-in-human
Official Title
A Randomized, Double-blind, Placebo Controlled Study to Assess the Safety and Tolerability of HAL-MRE1 Subcutaneous Immunotherapy in Adult Subjects With Ragweed Induced Allergic Rhinitis/Rhinoconjunctivitis With or Without Asthma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
November 21, 2018 (Actual)
Primary Completion Date
May 17, 2019 (Actual)
Study Completion Date
May 17, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HAL Allergy

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The aim of this first-in-human phase I study is to assess the safety and tolerability of HAL-MRE1 subcutaneous immunotherapy in subjects suffering from ragweed pollen-induced allergic rhinitis/rhinoconjunctivitis with or without asthma. The study has 4 treatment groups: 1 placebo group and 3 groups treated with different doses of HAL-MRE1.
Detailed Description
A chemically modified, aluminum hydroxide adsorbed ragweed extract (HAL-MRE1) for subcutaneous administration was developed for the treatment of ragweed pollen-induced allergic rhinitis/rhinoconjunctivitis (ARC) with or without asthma. The aim of this first-in-human phase I study is to assess the safety and tolerability of HAL-MRE1 subcutaneous immunotherapy in subjects suffering from ragweed pollen-induced ARC with or without asthma. The study will consist of 3 staggered cohorts of 15 subjects each who are randomly assigned to the active or placebo group in a 2:1 manner using block randomization. A one month gap must be maintained between the end of the ragweed pollen peak season (2018) and subject randomization into the study. The study has seasonal constraints; subjects with concomitant tree and/or grass pollen allergies must complete study treatment before any allergy symptoms due to tree and/or grass pollen exposure develop or start study treatment after the symptoms caused by the tree and/or grass pollen exposure have disappeared.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rhinitis, Allergic, Rhinoconjunctivitis, Allergic
Keywords
Subcutaneous immunotherapy, Ragweed pollen, Allergic rhinitis/rhinoconjunctivitis, Safety, Tolerability

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HAL-MRE1 0 AUeq
Arm Type
Placebo Comparator
Arm Description
15 subjects will receive placebo. Subjects will receive 7-9 incremental weekly injections. All doses will be subcutaneously injected in a double-blind fashion in the upper arm.
Arm Title
HAL-MRE1 5,000 AUeq
Arm Type
Experimental
Arm Description
10 subjects will receive HAL-MRE1 5,000 AUeq. Subjects will receive 6-8 incremental weekly injections until reaching the maximum dose of 5,000 AUeq. Subsequently, 1 repeated maximum dose injection will be given 1 week later (total treatment period will be approximately 7-9 weeks). All doses will be subcutaneously injected in a double-blind fashion in the upper arm.
Arm Title
HAL-MRE1 10,000 AUeq
Arm Type
Experimental
Arm Description
10 patients will receive HAL-MRE1 10,000 AUeq. Subjects will receive 6-8 incremental weekly injections until reaching the maximum dose of 10,000 AUeq. Subsequently, 1 repeated maximum dose injection will be given 1 week later (total treatment period will be approximately 7-9 weeks). All doses will be subcutaneously injected in a double-blind fashion in the upper arm.
Arm Title
HAL-MRE1 20,000 AUeq
Arm Type
Experimental
Arm Description
10 patients will receive HAL-MRE1 20,000 AUeq. Subjects will receive 6-8 incremental weekly injections until reaching the maximum dose of 20,000 AUeq. Subsequently, 1 repeated maximum dose injection will be given 1 week later (total treatment period will be approximately 7-9 year). All doses will be subcutaneously injected in a double-blind fashion in the upper arm.
Intervention Type
Biological
Intervention Name(s)
HAL-MRE1
Intervention Description
HAL-MRE1 is a liquid suspension for subcutaneous administration containing aluminum hydroxide adsorbed modified allergens extracted from ragweed pollen.
Primary Outcome Measure Information:
Title
Occurence of local and systemic reactions
Description
Number, intensity and seriousness of early (within 30 mins from injection), delayed (within 30mins and 3 hours from injection) and late (from 3 hours to 24 hours after injection) local reactions (>8 cm wheal size swelling at injection site) as well as early, delayed and late systemic reactions.
Time Frame
Through study completion, approximately 10 weeks
Secondary Outcome Measure Information:
Title
Occurence of other local reactions
Description
Number, intensity and seriousness of other local reactions like itching, pain and redness at injection site.
Time Frame
Through study completion, approximately 10 weeks
Title
Occurrence of treatment emergent adverse events
Description
Treatment emergent adverse events will be collected by reporting of adverse events and by clinical relevant changes in e.g. laboratory values, vital signs, physical exam, and lung function in plasma and urine
Time Frame
Through study completion, approximately of 10 weeks
Title
Number of subjects that reach maximum dose
Description
The number of subjects in each cohort who reach the maximum dose is indicative of HAL-MRE1 tolerability.
Time Frame
Through study completion, approximately of 10 weeks
Title
Number of injections to reach maintenance dose
Description
The number of injections that subjects in each cohort need to reach the maximum dose will provide an indication of HAL-MRE1 tolerability.
Time Frame
Through study completion, approximately of 10 weeks
Title
Immunoglobulin Levels
Description
Short term pharmacodynamic effects of HAL-MRE1 will be measured by determining the change in serum levels of allergen specific immunoglobulins (IgE, IgG and IgG4) pre- and post-study treatment in the HAL-MRE versus placebo treated groups.
Time Frame
Pre-treatment and after the repeated maintenance dose visit (after 8 to 10 weeks)
Title
Change in wheal size after skin prick test
Description
Exploratory efficacy data will be obtained by measuring the change in wheal size following skin prick test with ragweed extract pre- and post-treatment in the HAL-MRE1 versus placebo treated groups.
Time Frame
Pre-treatment and after the repeated maintenance dose visit (after 8 to 10 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent. Male or female subjects aged ≥18 and ≤65 years. Documented diagnosis of allergic rhinitis/rhinoconjunctivitis (ARC) to ragweed pollen. A documented diagnosis is a documented medical history of ARC symptoms that required treatment after ragweed pollen exposure. Subjects experienced allergy symptoms that required treatment during the previous 2 ragweed seasons, with or without concomitant asthma (asthma must be controlled). Positive nasal provocation test for ragweed pollen at screening or within the last 6 months. Positive skin prick test to ragweed allergen at screening or within the last 6 months. Positive serum specific IgE test for ragweed allergen (IgE level ≥0.7 U/mL). Forced expiratory volume >70 % or peak expiratory flow >80 % of predicted value. For asthmatic subjects: asthma control test (ACT) score ≥20. Subjects are capable and willing to maintain a log of adverse events and concomitant medication throughout the study, as well as to complete a diary 24 hours post investigational medical product injection. Negative pregnancy test at screening for females of childbearing potential. Females of childbearing age must be using an effective method of contraception to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of participation in the study. Contraceptive measures considered adequate are: hormonal contraceptives such as contraceptive pills, transdermal patches, intrauterine devices, intrauterine system implants, or vaginal rings (started at least 4 weeks prior to investigational medical product administration). double barrier methods e.g. condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent. sterilization (male or female). participants who are postmenopausal (12 consecutive months without a period) for at least 2 years. sexual abstinence or having no sexual relationship with a man. Exclusion Criteria: History of anaphylaxis with cardio respiratory symptoms (food allergy, venom allergy, drugs or/and idiopathic reaction). Alcohol, drug or medication abuse in the past. Any clinically significant abnormal laboratory parameter at screening as per investigator's discretion. Clinically relevant sensitization to other allergens if clinical symptoms are expected during the study. Uncontrolled asthma. Participation in a clinical interventional study within the last 3 months (e.g. new investigational drug or biological), or plans to participate in another clinical trial during this study, or participation in an observational study (e.g. post marketing study) within the last 30 days unless the observational study aimed to investigate the intradermal test. Subjects who received immunotherapy for any specific allergen 3 years prior to screening or during the study period. Subjects who were ever treated with any ragweed allergen specific immunotherapy. Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs. Subjects undergoing any immunosuppressive treatment (including anti-IgE therapy) within the last 6 months prior to inclusion in the study as well as during the study. Active malignancies or any malignant disease during the 5 years prior to screening. Severe uncontrolled diseases that, in the opinion of the investigator, could increase the risk for subjects participating in the study, including but not limited to: any severe or unstable lung diseases; endocrine diseases; clinically significant renal or hepatic diseases, or hematological disorders; or severe ongoing symptomatic allergic diseases. Active or acute inflammation or infection of the target organs (nose, eyes) at screening. Diseases with a contra-indication for the use of adrenaline (e.g. hyperthyroidism, glaucoma). Lactation. Severe psychiatric, psychological, or neurological disorders. Subjects who have any direct working relationship with the (sub-) investigator or study site personnel or are first degree relatives or partners of the investigator or study site personnel or are employees of the sponsor. Known allergy or hypersensitivity to an excipient in the study drug or placebo. Subjects receiving the prohibited previous and concomitant medication.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Couroux, MD
Organizational Affiliation
Inflamax Research Ltd.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Inflamax Research Inc.
City
Mississauga
ZIP/Postal Code
ON L4W 1A4
Country
Canada

12. IPD Sharing Statement

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HAL-MRE1 Subcutaneous Immunotherapy in Ragweed Allergic Patients First-in-human

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