## Protocol Section
### Identification Module
**NCT ID:** NCT02975479

**Brief Title:** Intralymphatic Immunotherapy in Increasing Doses, Substudy

**Official Title:** Intralymphatic Immunotherapy in Increasing Doses up to 10 000 SQ-U - a Human Randomized Clinical Trial. Substudy.

#### Organization Study ID Info
**ID:** 2015-001259-63 substudy
#### Organization
**Class:** OTHER
**Full Name:** Karolinska Institutet
### Status Module
#### Completion Date
**Date:** 2022-06-20

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-06-24

**Type:** ACTUAL

**Last Update Submit Date:** 2022-06-22

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2022-06-20

**Type:** ACTUAL

#### Start Date
**Date:** 2016-05

**Status Verified Date:** 2020-10

#### Study First Post Date
**Date:** 2016-11-29
**Type:** ESTIMATED
**Study First Submit Date:** 2016-11-24
**Study First Submit QC Date:** 2016-11-28
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Skane University Hospital

**Class:** OTHER

**Name:** Karolinska University Hospital

#### Lead Sponsor

**Class:** OTHER

**Name:** Karolinska Institutet

#### Responsible Party

**Investigator Affiliation:** Karolinska Institutet

**Investigator Full Name:** Lars Olaf Cardell

**Investigator Title:** Professor, Head of Division, M.D.

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The study evaluates the safety and effect of intralymphatic allergen specific immunotherapy in increasing doses. Patients with allergy to grass or birch will be treated with three intralymphatic injections in an up-dosing protocol; 1000 SQ-U, 3000 SQ-U and 10 000 SQ-U, or placebo.

\*\*\*IMPORTANT INFORMATION!\*\*\* The up-dosing protocol is changed due to adverse events at 5000 SQ-U. One patient had general utricaria 15 minutes after injection (moderate reaction). One patient had a serious adverse event with anaphylactic reaction 6 minutes after intralymphatic injection. (1000 SQ-U and 3000 SQ-U have been given with no serious adverse events.) New regimen: 1000 SQ-U, 3000 SQ-U, 3000 SQ-U.

**Detailed Description:** 40 patients with seasonal allergic rhinitis will be recruited. Study subjects are randomized to intralymphatic injections with placebo or ALK Alutard 5-grasses or birch. Injections are given with 4-5 (-7) weeks interval.

### Conditions Module

**Conditions:**

- Rhinitis, Allergic, Seasonal

**Keywords:**

- Hay fever

- Pollen allergy

- Allergic rhinitis

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 40

**Type:** ESTIMATED

**Phases:**

- PHASE2

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** ALK Diluent, ATC-code V07AB. 3 injections with 4-7 weeks interval.

**Intervention Names:**

- Drug: ALK Diluent

**Label:** Intralymphatic placebo injections

**Type:** PLACEBO_COMPARATOR

#### Arm Group 2

**Description:** ATC-code V01AA02. 3 injections with 4-7 weeks interval in an up-dosing protocol; 1000 SQ-U, 3000 SQ-U, 10000 SQ-U.

\*\*\*IMPORTANT INFORMATION! The up-dosing protocol is changed due to an adverse event at the last injection. New regimen: 1000 SQ-U, 3000 SQ-U, 3000 SQ-U. \*\*\*

**Intervention Names:**

- Drug: ALK Alutard SQ 5-grasses or ALK Alutard Birch

**Label:** Intralymphatic active injections

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Intralymphatic placebo injections

**Name:** ALK Diluent

**Other Names:**

- 0,3% human albumin. ATC-code V07AB

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Intralymphatic active injections

**Description:** Depot formulation of relevant allergen adsorbed to aluminium hydroxide in a suspension.

**Name:** ALK Alutard SQ 5-grasses or ALK Alutard Birch

**Other Names:**

- Allergen, grass pollen. ATC-code V01AA02 or V01AA05

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale) and medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids).

**Measure:** Mean combined daily symptoms-and-medications-score

**Time Frame:** Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).

#### Secondary Outcomes

**Description:** Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale)

**Measure:** Mean total daily symptoms score

**Time Frame:** Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).

**Description:** Daily scoring of medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids).

**Measure:** Mean total daily medications score

**Time Frame:** Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).

**Description:** The study subjects will be intranasally challenged with allergen and symptom score questionnaires are filled out pre-provocation and 5, 10 and 30 min post-provocation.

**Measure:** Change in subjective allergic symptoms following nasal allergen provocation

**Time Frame:** Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.

**Description:** Juniper Rhinitis quality of life questionnaire (RQLQ) questionnaires

**Measure:** Effects on quality of life

**Time Frame:** During peak pollen season which will be up to 6 months after completed treatment.

**Description:** Skin prick test

**Measure:** Short term change of skin reactivity

**Time Frame:** Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.

**Measure:** S-IgE Grass or Birch

**Time Frame:** Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment

**Measure:** S-IgG4 Grass or Birch

**Time Frame:** Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment

**Measure:** Registration of adverse event

**Time Frame:** From the first injection to 30 days after the last injections has been given

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Seasonal allergic symptoms for birch and/or grass verified by skin prick test,
* Accepted informed consent

Exclusion Criteria:

* Pregnancy or nursing
* Autoimmune or collagen disease (known)
* Cardiovascular disease
* Perennial pulmonary disease
* Hepatic disease
* Renal disease
* Cancer
* Any medication with a possible side-effect of interfering with the immune response
* Previous immuno- or chemotherapy
* Chronic diseases
* Other upper airway disease (non-allergic sinusitis, nasal polyps, chronic obstructive and restrictive lung disease)
* Disease or conditions rendering the treatment of anaphylactic reactions difficult (symptomatic coronary heart diseases, severe arterial hypertension and treatment with β-blockers)
* Major metabolic disease
* Known or suspected allergy to the study product
* Alcohol or drug abuse
* Mental incapability of coping with the study
* Withdrawal of informed consent

**Maximum Age:** 55 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Lund

**Country:** Sweden

**Facility:** Allergic Unit at the Department of Oto-Rhino-Laryngology at Skåne University Hospital Lund

**Zip:** 221 85

**Location 2:**

**City:** Stockholm

**Country:** Sweden

**Facility:** ENT-department, Karolinska University Hospital Huddinge (ENT-department B51)

**Zip:** 141 86

#### Overall Officials

**Official 1:**

**Affiliation:** Karolinska Institutet

**Name:** Lars-Olaf Cardell, Professor

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** Hellkvist L, Hjalmarsson E, Weinfeld D, Dahl A, Karlsson A, Westman M, Lundkvist K, Winqvist O, Georen SK, Westin U, Cardell LO. High-dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase. Allergy. 2022 Mar;77(3):883-896. doi: 10.1111/all.15042. Epub 2021 Aug 29.

**PMID:** 34379802

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000012141

- Term: Respiratory Tract Infections

- ID: D000007239

- Term: Infections

- ID: D000009668

- Term: Nose Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000010038

- Term: Otorhinolaryngologic Diseases

- ID: D000012130

- Term: Respiratory Hypersensitivity

- ID: D000006969

- Term: Hypersensitivity, Immediate

- ID: D000006967

- Term: Hypersensitivity

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC01

- Name: Infections

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC09

- Name: Ear, Nose, and Throat Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC26

- Name: Wounds and Injuries

### Condition Browse Module - Browse Leaves

- ID: M10018

- Name: Hypersensitivity

- Relevance: LOW

- As Found: Unknown

- ID: M15049

- Name: Rhinitis

- Relevance: HIGH

- As Found: Rhinitis

- ID: M30545

- Name: Rhinitis, Allergic

- Relevance: HIGH

- As Found: Rhinitis, Allergic

- ID: M2454

- Name: Hyperthermia

- Relevance: LOW

- As Found: Unknown

- ID: M8464

- Name: Fever

- Relevance: LOW

- As Found: Unknown

- ID: M9345

- Name: Rhinitis, Allergic, Seasonal

- Relevance: HIGH

- As Found: Rhinitis, Allergic, Seasonal

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14978

- Name: Respiratory Tract Infections

- Relevance: LOW

- As Found: Unknown

- ID: M12604

- Name: Nose Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12961

- Name: Otorhinolaryngologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14967

- Name: Respiratory Hypersensitivity

- Relevance: LOW

- As Found: Unknown

- ID: M10020

- Name: Hypersensitivity, Immediate

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000012220

- Term: Rhinitis

- ID: D000065631

- Term: Rhinitis, Allergic

- ID: D000006255

- Term: Rhinitis, Allergic, Seasonal

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Gast

- Name: Gastrointestinal Agents

### Intervention Browse Module - Browse Leaves

- ID: M2853

- Name: Immunomodulating Agents

- Relevance: LOW

- As Found: Unknown

- ID: M3877

- Name: Aluminum Hydroxide

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
