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

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

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.

Study Overview

• Status: Completed
• Conditions: Birch Pollen Allergy
• Intervention / Treatment: Biological: DM-101; Biological: Placebo to match DM-101

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland
    • Clinical Research Services Turku

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DM-101 Single Dose; Participants received a single subcutaneous (SC) dose of DM-101 30 ng on Day 1	Biological: DM-101; DM-101 administered by subcutaneous (SC) injection
Placebo Comparator: Placebo Single Dose; Participants received a single SC injection of placebo on Day 1	Biological: Placebo to match DM-101; Placebo to match DM-101 administered by SC injection
Experimental: DM-101 Low Multiple Ascending Doses (MAD); 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; DM-101 administered by subcutaneous (SC) injection
Placebo Comparator: Placebo Low MAD; Participants received 5 biweekly administered SC injections of placebo on Day 1,14, 28, 42, and 56.	Biological: Placebo to match DM-101; Placebo to match DM-101 administered by SC injection
Experimental: DM-101 High MAD; 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; DM-101 administered by subcutaneous (SC) injection
Placebo Comparator: Placebo High MAD; 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; Placebo to match DM-101 administered by SC injection
Experimental: DM-101 2-Day Ultra-Rush Dose Escalation; 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; DM-101 administered by subcutaneous (SC) injection
Placebo Comparator: Placebo 2-Day Ultra-Rush Dose Escalation; Participants received 9 SC injections of placebo during Day 1 and Day 2.	Biological: Placebo to match DM-101; Placebo to match DM-101 administered by SC injection

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Desentum Oy
• Investigators: Study Director: Anna Nilson, Desentum Oy; Principal Investigator: Mika Scheinin, Clinical Research Services Turku

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2020
• Primary Completion (Actual): May 31, 2021
• Study Completion (Actual): May 31, 2021

Study Registration Dates

• First Submitted: February 10, 2020
• First Submitted That Met QC Criteria: February 10, 2020
• First Posted (Actual): February 12, 2020

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Nose Diseases; Rhinitis, Allergic; Rhinitis; Hypersensitivity; Rhinitis, Allergic, Seasonal
• Other Study ID Numbers: DM-101-C-001; 2019-001936-67 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: Anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to patient level data and related study documents. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants after Desentum has received marketing authorization from major health authorities (e.g., FDA, EMA), has the legal authority to share the data, and has made the study results publicly available.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No