Dose Selection Study of Efficacy and Safety of Different Doses of Grass MATA MPL and Grass MATA Using mEECs™

NCT02582073 | Completed Phase 2 DMC

• 1 other identifier: GrassMATAMPL204
• Study Type: interventional
• Target: 265
• Locations: 1 country
• Sites: 1

Brief Summary

There is increasing evidence that the effectiveness of allergy immunotherapy to control symptoms of rhinoconjunctivitis is related to the cumulative dose of allergen or allergoid administered during a single regimen of subcutaneous (SC) injections or of sublingual administration. The current therapeutic dose regimen for Grass MATA MPL is a course of four injections of 300, 800, 2000 and 2000 SU (Standardized Units), administered at weekly intervals (cumulative dose 5100 SU). Two new cumulative doses of the Grass MATA MPL 10200 SU and 18200 SU are being developed to compare with the current dose. The study is designed to explore the benefit/risk of increasing the cumulative allergen dose of the Grass MATA MPL immunotherapy comparing these doses with the current dose of Grass MATA MPL, Grass MATA (without MPL) and placebo.

Conditions

Seasonal Allergic Rhinitis

Outcome Measures

Primary Outcomes (1)

• Post-treatment TSS

  The primary efficacy endpoint will be the mean average of the last three TSS measurements recorded in each of the four post-treatment Visits 12 15. TSS will be measured during the four post-treatment mEEC™ sessions conducted on consecutive days 12-15, and is defined as the sum of individual NSS (rhinorrhea, congestion, sneezing and itchiness) and NNSS (itchy/gritty eyes, tearing/watery eyes, red/burning eyes and ear/palate itching).

  21-28 days after the last injection

Secondary Outcomes (6)

• Frequency of local adverse events (AEs)

  A Local AE is located at the injection site of study medication, occurring within 24 hours after the injection.

• Frequency of systemic adverse events (AEs)

  24 hours following each injection

• Frequency of other AEs

  Up to 1 year following injections

• Frequency of AEs of special interest (AESI)

  Up to 1 year following injections

• Safety laboratory values

  Up to 12 weeks

Study Arms (6)

Placebo (0.5ml)

PLACEBO COMPARATOR

Six 0.5ml injections of placebo consisting of L-Tyrosine, Ph. Eur 2%

Biological: Placebo (0.5ml)

Placebo (1.0ml)

PLACEBO COMPARATOR

Six 1.0ml injections of placebo consisting of L-Tyrosine, Ph. Eur 2%

Biological: Placebo (1.0ml)

Grass MATA MPL (0.5ml) 5100SU

EXPERIMENTAL

Six 0.5 mL injections sequentially of placebo, placebo, 300, 800, 2000 and 2000 SU of Grass MATA with 50 µg/0.5 mL of MPL® adjuvant adsorbed to L tyrosine (2%) and 0.5% phenol (cumulative dose 5100SU).

Biological: Placebo (0.5ml); Biological: Grass MATA MPL (0.5ml) 5100SU

Grass MATA MPL (1.0ml) 10200SU

EXPERIMENTAL

Six 1.0 mL injections sequentially of placebo, placebo, 600, 1600, 4000 and 4000 SU of Grass MATA per 1.0 mL and 50 µg/1.0 mL of MPL® adjuvant adsorbed to L tyrosine (2%) and 0.5% phenol (cumulative dose 10200 SU).

Biological: Placebo (1.0ml); Biological: Grass MATA MPL (1.0ml) 10200SU

Grass MATA MPL (1.0ml) 18200SU

EXPERIMENTAL

Six 1.0 mL injections sequentially of placebo, 600, 1600, 4000, 4000, 4000 and 4000 SU of Grass MATA per 1.0 mL and 50 µg/1.0 mL of MPL® adjuvant adsorbed to L tyrosine (2%) and 0.5% phenol (cumulative dose 18200 SU).

Biological: Placebo (1.0ml); Biological: Grass MATA MPL (1.0ml) 18200SU

Grass MATA (0.5ml) 5100SU

ACTIVE COMPARATOR

Six 0.5ml injections sequentially of placebo, placebo, 300, 800, 2000 and 2000 SU of Grass MATA adsorbed to L tyrosine (2%) and 0.5% phenol (cumulative dose 5100SU).

Biological: Placebo (0.5ml); Biological: Grass MATA (0.5ml) 5100SU

Interventions

Placebo (0.5ml) BIOLOGICAL

Grass MATA (0.5ml) 5100SU; Grass MATA MPL (0.5ml) 5100SU; Placebo (0.5ml)

Placebo (1.0ml) BIOLOGICAL

Grass MATA MPL (1.0ml) 10200SU; Grass MATA MPL (1.0ml) 18200SU; Placebo (1.0ml)

Grass MATA MPL (0.5ml) 5100SU BIOLOGICAL

Grass MATA MPL (0.5ml) 5100SU

Grass MATA MPL (1.0ml) 10200SU BIOLOGICAL

Grass MATA MPL (1.0ml) 10200SU

Grass MATA MPL (1.0ml) 18200SU BIOLOGICAL

Grass MATA MPL (1.0ml) 18200SU

Grass MATA (0.5ml) 5100SU BIOLOGICAL

Grass MATA (0.5ml) 5100SU

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18 to 50 years inclusive
• Allergy to grass pollen allergen, defined by:
• A history of moderate to severe symptoms of seasonal allergic rhinitis and/or conjunctivitis due to grass pollen exposure that required repeated use of antihistamines, nasal steroids, and/or leukotriene modifiers for relief of symptoms, confirmed by the patient record if available.
• A positive skin prick test for grass pollen allergen (wheal (longest diameter) of ≥ 5 mm greater than the negative control after skin prick testing) at Visit 1.
• Specific IgE for grass pollen as documented by a specific IgE immunoassay, or equivalent test, with class ≥ 2 to grass pollen mix. Results from tests conducted under a generalized screening protocol within the past six months may be used and will not need to be repeated at V1 provided a copy of the test results is added to the source file.
• Positive skin prick test to histamine (wheal (longest diameter) ≥ 3 mm greater than the negative control)
• Negative skin prick test to the negative control (redness with wheal ≤ 2 mm is acceptable)
• For asthmatic patients: Forced expiratory volume (FEV) in 1 second (FEV1) ≥ 80% of National Health and Nutrition Examination Surveys (NHANES) predicted, with a FEV1/Forced Vital Capacity (FVC) ratio ≥ 70%
• Obtain the minimum qualifying symptom scores by the final pre treatment EEC visit to be enrolled into the study. Minimum qualifying TSS is at least 12 out of a possible 24 on at least one recording time, a TNSS score of at least 7 out of a possible 12 on at least one recording time, and a rhinorrhea score of at least 2 on at least two diary cards.
• Observe the drug washout times for antihistamines, steroids etc. as specified in the protocol prior to screening (Visit 1). The use of other medications will be permitted if they are not expected to interfere with the ability of the patient to participate in the study and provided they have been on a stable regimen (i.e., the same dosage and administration) for six weeks prior to screening
• Males or non pregnant, non lactating females who are:
• Post menopausal (defined as at least 12 months natural spontaneous amenorrhea or at least 6 weeks following surgical menopause, i.e. bilateral oophorectomy)
• Naturally or surgically sterile (hysterectomy; bilateral oophorectomy; bilateral tubal ligation with surgery at least 6 weeks prior to study initiation)
• Of childbearing potential - with negative urinary and serological pregnancy test and use at least one of the following contraception methods:
• i. Stable hormonal contraceptive for ≥ 90 days prior to Visit 1 and for at least 7 days after the final injection. If \< 90 days prior to the study, additional use of a double barrier method until 90 days reached is required.

You may not qualify if:

• In the presence of symptoms outside the grass pollen season coupled with a positive skin test to a perennial allergen, if as assessed by the Investigator the patient is unable to avoid the offending allergen.
• Concurrent disease that might complicate or interfere with investigation or evaluation of the study medications or the skin prick test result, such as:
• Nasal polyposis
• Any ocular disorder (other than allergic conjunctivitis) including presumed infectious ocular disease (bacterial, fungal, viral, etc.), which could interfere with the evaluation of the study medication
• Rhinitis medicamentosa
• Documented evidence of acute or significant chronic sinusitis or upper or lower respiratory tract infection within 30 days before Visit 2 as determined by the Investigator
• Asthma, with the exception of mild asthma as, to lessen confounding by asthma medications. Patients taking corticosteroids for asthma at doses higher than budesonide MDI 400µg once a day or equivalent, as defined by the current GINA guideline, will be excluded.
• Emergency room visit or admission for asthma in the 12 months prior to Visit 1 or history of a life-threatening asthma attack ever
• Presence of acute or subacute atopic dermatitis, chronic dermatitis, urticaria factitia, or urticaria due to physical/chemical influence
• Presence of secondary alterations at the affected organ (i.e., emphysema, and bronchiectasis )
• Current diagnosis of Type I diabetes. Patients with Type II diabetes will only be allowed to participate at the discretion of the Investigator
• Autoimmune disease (e.g., of liver, kidney, lung, thyroid, nervous system, rheumatoid diseases) sarcoidosis, or NI disease (e.g., optic neuritis, multiple sclerosis or other demyelinating disease, encephalitis or encephalomyelitis, myelitis/transverse myelitis, myasthenia gravis, Guillain Barré syndrome, unexplained transitory neurological events)
• History of cancer (excluding basal cell carcinoma) or concomitant illness (e.g., cardiovascular, pulmonary, metabolic, renal, hepatic, gastrointestinal, dermatologic, venereal, hematologic, neurologic, or psychiatric diseases or disorders) that, in the opinion of the Investigator, would pose a safety risk or compromise the interpretation of efficacy for this grass immunotherapy
• Use of oral, intramuscular, intravenous corticosteroids, or potent or super-potent topical corticosteroids, from 30 days prior to screening up to Visit 16
• Any systemic disorder that could interfere with the evaluation of the study medications

Sponsors & Collaborators

• Allergy Therapeutics: lead

Study Sites (1)

Inflamax Research Inc.

Neptune City, New Jersey, 07753, United States

Location

MeSH Terms

Conditions

Rhinitis, Allergic, Seasonal

Condition Hierarchy (Ancestors)

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

Study Officials

• Tim Higenbottam, DSc MD FRCP

  Allergy Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2015
• First Posted: October 21, 2015
• Study Start: November 7, 2015
• Primary Completion: May 5, 2016
• Study Completion: April 28, 2017
• Last Updated: January 29, 2021

Record last verified: 2021-01

Locations

US (1)