Study to Evaluate Safety and Tolerability of sc Immunotherapy With DM-101 in Adults With Birch Pollen Allergy

Study Overview
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Brief Summary
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Randomized, double-blind placebo-controlled phase I study to investigate the safety and tolerability of ascending doses of DM-101 in adult subjects with birch pollen allergy.

Detailed Description
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The study will be carried out in a single study site located in Finland.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Dose Escalation Study to Evaluate the Safety and Tolerability of Subcutaneous Immunotherapy With DM-101 in Adults With Birch Pollen Allergy

Conditions
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Birch Pollen Allergy

Intervention / Treatment
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* Biological: DM-101
* Biological: Placebo to match DM-101


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Males or females, aged 18 to 65 years Good general health A documented clinical history of birch pollen-induced allergic rhinitis or rhinoconjunctivitis with symptoms that interfere with daily activities or sleep and remain bothersome despite the use of relevant symptomatic medication, and have been present over, at least, 2 allergy seasons. Bet v 1 specific serum IgE ≥ 0.7 kU/L Positive SPT to birch pollen allergen, with a wheal diameter ≥ 5 mm Body weight ≥50 kg and body mass index (BMI) within the range 18-35 kg/m2. Key Exclusion Criteria: History or findings on physical examination of any significant disease or disorder which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, influence the results of the study or the subject's ability to participate in the study. Current diagnosis of asthma (other than seasonal during the birch pollen allergy season), requiring Global Initiative for Asthma (GINA) Step 2 or higher treatment, or asthma partially controlled or uncontrolled according to GINA classification in the 6 months before Screening. History of asthma deterioration that resulted in emergency treatment or hospitalisation in the 12 months before screening, or a life-threatening asthma attack at any time in the past. Forced Expiratory Volume in one second (FEV1) < 70% of predicted, regardless of asthma status at screening or baseline assessment at the first dosing visit. History of severe drug allergy, severe angioedema or systemic allergic reaction of Grade 3 or greater, according to the World Allergy Organization (WAO) scale, due to any cause.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 4 sequential study cohorts with ascending DM-101 doses. In each cohort two treatment arms: placebo and active drug
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DM-101 Single Dose<br>Participants received a single subcutaneous (SC) dose of DM-101 30 ng on Day 1 | Biological: DM-101<br>* DM-101 administered by subcutaneous (SC) injection<br>|
| Placebo Comparator: Placebo Single Dose<br>Participants received a single SC injection of placebo on Day 1 | Biological: Placebo to match DM-101<br>* Placebo to match DM-101 administered by SC injection<br>|
| Experimental: DM-101 Low Multiple Ascending Doses (MAD)<br>Participants received 5 biweekly administered SC doses of DM-101 as follows: 30 ng on Day 1,50 ng on Day 14, 100 ng on Day 28, 42, and 56. | Biological: DM-101<br>* DM-101 administered by subcutaneous (SC) injection<br>|
| Placebo Comparator: Placebo Low MAD<br>Participants received 5 biweekly administered SC injections of placebo on Day 1,14, 28, 42, and 56. | Biological: Placebo to match DM-101<br>* Placebo to match DM-101 administered by SC injection<br>|
| Experimental: DM-101 High MAD<br>Participants received 5 biweekly administered SC doses of DM-101 as follows: 30 ng on Day 1,50 ng on Day 14, 100 ng on Day 28, 200 ng (dose divided into two SC injections) on Day 42, and 300 ng (dose divided into three SC injections) on Day 56. | Biological: DM-101<br>* DM-101 administered by subcutaneous (SC) injection<br>|
| Placebo Comparator: Placebo High MAD<br>Participants received 5 biweekly administered SC injections of placebo as follows: single injection on Day 1, 14 and 28; two injections on Day 42; three injections on Day 56. | Biological: Placebo to match DM-101<br>* Placebo to match DM-101 administered by SC injection<br>|
| Experimental: DM-101 2-Day Ultra-Rush Dose Escalation<br>Participants received 9 SC doses of DM-101 as follows: 100, 250, 500, 1000, 2500, 5000, 10000 and 25000 ng during Day 1 and Day 2. | Biological: DM-101<br>* DM-101 administered by subcutaneous (SC) injection<br>|
| Placebo Comparator: Placebo 2-Day Ultra-Rush Dose Escalation<br>Participants received 9 SC injections of placebo during Day 1 and Day 2. | Biological: Placebo to match DM-101<br>* Placebo to match DM-101 administered by SC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Emergent Adverse Events | Number of All Treatment Emergent Adverse Events (TEAEs) in Subjects Receiving DM-101 Compared to Placebo | From the first dose until 28 days following the last dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and Severity of Systemic Allergic Reactions (SARs) in Subjects Receiving DM-101 Compared to Placebo | Severity of SARs are graded from Grade 1 to 5 (Grade 5 being fatal) as defined by WAO Subcutaneous Immunotherapy Systemic Reaction Grading System. | From the first dose until 28 days following the last dose. | 
| Number and Severity of Local Injection Site Reactions (LISRs) in Subjects Receiving DM-101 Compared to Placebo | Pain, tenderness, erythema/redness and induration/swelling at the injection site was assessed after each injection using a 4-point scale (Grade 1 = mild, Grade 4 = severe) as defined in the study protocol. | From the first dose until 28 days following the last dose. | 
| Subjects Reaching the Pre-defined DM-101 Dose | Proportion of subjects reaching the pre-defined, admissible dose in each DM-101 dosing group | From the first dose until 28 days following the last dose. |