Efficacy and Safety of SUBLIVAC Phleum for Immunotherapy of Grass Pollen-Allergy

NCT02556801 | Completed Phase 2 Results DMC

• 1 other identifier: SP/0047
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess safety, tolerability and demonstrate a dose response signal using Total Symptom Score (TSS), based on challenges with grass pollen in an Environmental Exposure Chamber (EEC), followed by estimation of the minimum effective dose of SUBLIVAC FIX Phleum (SP) after 10 months of treatment compared to placebo. The study has 4 treatment groups: 3 different doses of SP and placebo will be tested.

Conditions

Allergic Rhinitis; Allergic Rhinoconjunctivitis

Keywords

Sublingual immunotherapy; Dose range finding; Grass pollen; Allergic rhinitis/rhinoconjunctivitis; Immunogenicity

Outcome Measures

Primary Outcomes (1)

• Mean Total Symptom Score (TSS) After 10 Months of Treatment (Visit 6) Compared to Placebo

  The primary endpoint was the TSS after 10 months of treatment (at visit 6). The mean TSS at visit 6 was calculated as an average of all non-missing TSS scores between 1 and 6 hours after start of Environmental Exposure Chamber (EEC) challenge at visit 6. TSS was computed as the sum of individual scores for eight nasal and non-nasal symptoms (rhinorrhea, congestion, sneezing, itchiness, itchy/gritty eyes, tearing/watery eyes, red/burning eyes, and ear/palate itching). Each of eight symptoms was rated on a scale of 0-3 as follows: 0, none; 1, mild; 2, moderate; 3, severe. The range of TSS is from 0 to 24 units on a scale. The highest the score, the more severe symptoms a subject experiences. Negative change of TSS between baseline and visit 6 was expected (reduced symptoms), more negative change at visit 6 versus baseline represents better outcome of the study.

  10 months after treatment start (baseline - Visit 2)

Secondary Outcomes (8)

• Change From Baseline in Mean Total Symptom Score (TSS) After 10 Months of Treatment (Visit 6)

  10 months after treatment start compared to first day of treatment (TSS at baseline measured at Visit 2, before IMP administration)

• Change From Baseline in Mean Total Symptom Score (TSS) After 5 Months of Treatment (Visit 4)

  5 months after treatment start compared to first day of treatment (TSS at baseline measured at Visit 2, before IMP administration)

• Change From Baseline in Mean Total Nasal Symptom Score (TNSS) After 10 Months of Treatment (Visit 6)

  10 months after treatment start compared to first day of treatment (TSS at baseline measured at Visit 2, before IMP injection)

• Change From Baseline in Mean Total Nasal Symptom Score (TNSS) After 5 Months of Treatment (Visit 4)

  5 months after treatment start compared to first day of treatment (TSS at baseline measured at Visit 2, before IMP injection)

• Mean Combined Symptom and Medication Scores (CSMS) During the Grass Pollen Season.

  during the grass pollen season: estimated between 6 and 10 months after start of treatment at Visit 2

Other Outcomes (2)

• Number and Severity of Local Reactions

  Ongoing during 10 months treatment period

• Number and Severity of Systemic Reactions

  Ongoing during 10 months treatment period

Study Arms (4)

SUBLIVAC FIX Phleum Prat. 0 AUN/ml

PLACEBO COMPARATOR

42 subjects received placebo (SUBLIVAC FIX Phleum Pratense 0 AUN/ml) sublingually. Subjects will start with one drop and add one drop each consecutive day until the maintenance dose of 5 drops per day is reached. Next treatment at maintenance dose is continued during 10 months.

Biological: SUBLIVAC FIX Phleum Prat.

SUBLIVAC FIX Phleum Prat. 10,000 AUN/ml

EXPERIMENTAL

42 subjects received SUBLIVAC FIX Phleum Pratense 10,000 AUN/ml) sublingually. Subjects will start with one drop and add one drop each consecutive day until the maintenance dose of 5 drops per day is reached. Next treatment at maintenance dose is continued during 10 months.

Biological: SUBLIVAC FIX Phleum Prat.

SUBLIVAC FIX Phleum Prat. 40,000 AUN/ml

EXPERIMENTAL

40 subjects received SUBLIVAC FIX Phleum Pratense 40,000 AUN/ml sublingually. Subjects will start with one drop and add one drop each consecutive day until the maintenance dose of 5 drops per day is reached. Next treatment at maintenance dose is continued during 10 months.

Biological: SUBLIVAC FIX Phleum Prat.

SUBLIVAC FIX Phleum Prat. 80,000 AUN/ml

EXPERIMENTAL

40 subjects received SUBLIVAC FIX Phleum Pratense 80,000 AUN/ml sublingually. Subjects will start with one drop and add one drop each consecutive day until the maintenance dose of 5 drops per day is reached. Next treatment at maintenance dose is continued during 10 months.

Biological: SUBLIVAC FIX Phleum Prat.

Interventions

SUBLIVAC FIX Phleum Prat. BIOLOGICAL

sublingual daily administration

SUBLIVAC FIX Phleum Prat. 0 AUN/ml; SUBLIVAC FIX Phleum Prat. 10,000 AUN/ml; SUBLIVAC FIX Phleum Prat. 40,000 AUN/ml; SUBLIVAC FIX Phleum Prat. 80,000 AUN/ml

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who signed informed consent.
• Subjects aged ≥18 and ≤65 years at signing of informed consent.
• Subjects with at least two-year clinical history of allergic rhinitis/rhinoconjunctivitis to grass pollen, with or without concomitant asthma (asthma must be controlled).
• Subjects with a forced expiratory volume at one second (FEV1) \>70% of the predicted value as measured during screening or documented within 1 year of study start.
• Subjects with a positive skin prick test (SPT) (mean wheal diameter of at least 3 mm larger than the negative control; negative control should be \<2 mm, histamine control should be positive (mean wheal diameter of at least 3 mm larger than the negative control)) for grass pollen assessed during screening or a documented positive response obtained within 1 year before screening.
• Subjects with a grass pollen specific IgE greater than or equal to 0.7 kiloUnits (kU)/L assessed during screening or a documented positive result obtained within 1 year before screening.
• Subjects with a TSS of at least 10/24 during baseline EEC challenge (V2) in combination with a staff assessed score of at least 2/3 for two objective TSS symptoms (i.e. running nose, sneezing or red eyes), during the baseline EEC challenge.

You may not qualify if:

• Subjects with (expected) clinically relevant symptoms at the timing of the scheduled EEC assessments at Visit 2 and Visit 6 due to concomitant sensitization i.e. positive SPT (mean wheal diameter of at least 3 mm larger than the negative control) and a history of allergic response to the causative allergen, at the discretion of the investigator.
• Patients with grass pollen induced asthma.
• Subjects who cannot tolerate the Baseline Challenge in the EEC.
• Subjects who received immunotherapy (SCIT or SLIT) with grass pollen allergens within the past 5 years.
• (Ongoing) allergen-specific immunotherapy with any allergen(s) during the study period.
• Subjects with unsuccessful allergen-specific immunotherapy within the past 5 years (e.g., but not limited to, prematurely stopped immunotherapy due to non-compliance, AEs or lack of therapeutic effect), at the discretion of the investigator.
• Subjects suffering from severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs.
• Subjects suffering from active malignancies or any malignant disease (except for localized basal cell cancers of the skin as long as they have been adequately treated and no recurrence within 3 months of screening visit) during 5 years prior to screening.
• Subjects suffering from severe uncontrolled diseases that could increase the risk for participating in the study, including but not limited to: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or haematological disorders at the discretion of the Investigator.
• Subjects who have active inflammation or infection of the target organs (nose, eyes or lower airways) at Visit 1.
• Subjects suffering from diseases with a contraindication for the use of adrenaline (e.g. hyperthyroidism, glaucoma).
• Subjects receiving vaccination within one week before start of therapy or during the up-dosing phase.
• Subjects receiving treatment with systemic steroids within 4 weeks before visit 1 and/or during the study.
• Subjects receiving treatment with systemic or local β-blockers anytime during the study.
• Subjects who participated in a clinical study within the last 3 months (e.g. new investigational drug or biological) or within the last 30 days (e.g. bio-equivalent drug), at the discretion of the Investigator.

Sponsors & Collaborators

• HAL Allergy: lead

Study Sites (1)

Inflamax Research Inc.

Mississauga, ON L4W 1A4, Canada

Location

MeSH Terms

Conditions

Rhinitis, Allergic

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Andrey Larionov, MD, Head of Clinical Development
• Organization: HAL Allergy

alarionov@hal-allergy.com

+31881959189

Study Officials

• Peter Couroux, MD

  Inflamax

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2015
• First Posted: September 22, 2015
• Study Start: September 1, 2015
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: September 13, 2019
• Results First Posted: September 13, 2019

Record last verified: 2019-08

Locations

CA (1)