Pivotal, Randomized, Open-Label, 3-Period Crossover Study to Assess the Efficacy and Safety of AM-301 on Allergic Symptoms During House Dust Mite Challenge in an Exposure Chamber in Study Participants With Perennial Allergic Rhinitis
Phase: NA
Conditions: Perennial Allergic Rhinitis, Rhinitis, Allergic
Sponsor: Altamira Medica Ltd.

CLINICAL STUDY 
PROTOCOL 
   C2D01121/ AM-301-CL-21-02  
                      Altamira Medica AG 
  
 
Cliantha Research    
CONFIDENTIAL 
Page 14 of 58 
     Version: Final 2.0  
Date: 27-SEP-2021 
 
4. 
STUDY SUMMARY 
Study Title 
 
A Pivotal, Randomized, Open-Label, 3-Period Crossover Study to Assess the Efficacy 
and Safety of AM-301 during House Dust Mite Challenge in an Environmental Exposure 
Chamber in Study participants with Perennial Allergic Rhinitis 
Protocol Number 
Sponsor Study Number: AM-301-CL-21-02 
Cliantha Research Study Number: C2D01121 
Study Phase 
 Pivotal Confirmatory Clinical Investigation 
Study Objectives 
Primary Objective 
To compare the efficacy of AM-301 Device between treated and non-treated subjects in 
the treatment of perennial allergic rhinitis (PAR) when evaluated in House Dust Mite 
(HDM) allergic study participants in an Environmental Exposure Chamber (EEC). 
Secondary Objective 
To compare the efficacy of AM-301 device between single and double applications per 
nostril of Altamira AM-301 Device in the treatment of perennial allergic rhinitis (PAR) 
when evaluated in House Dust Mite (HDM) allergic study participants in an 
Environmental Exposure Chamber (EEC). 
Study Endpoints 
Primary Efficacy Endpoint:  
Changes from baseline in TNSS at each post-dose assessment time points (0 to 3 hours) 
at Visit 3, Visit 4 and Visit 5 
Secondary Efficacy Endpoints:  
• 
Difference of TNSS at individual timepoints during house dust mite challenge in the 
EEC (0-180 min) between single and double application of AM-301 and no 
treatment.  
• 
Change from baseline in individual NSS at Visit 3, Visit 4 and Visit 5 
• 
Patient reported Global rating for efficacy at single application and double 
application of AM-301 during EEC treatment visits. 
• 
Investigator reported Global rating for efficacy for single and double application of 
AM-301 during EEC treatment visits. 
Safety endpoints: 
• 
Occurrence and severity of Adverse Events (AEs) and Serious Adverse Events 
(SAEs). 
• 
Patient reported Global rating for tolerability at single application and double 
application of AM-301 during EEC treatment visits. 
Investigator reported Global rating for tolerability for single and double application of 
AM-301 during EEC treatment visits. 
Study Design 
 
Randomized, open label, 3-Period crossover trial. The clinical trial will consist of 5 visits, 
followed by a follow-up telephone call.  The total period of the trial will be approximately 
65 days.  
The 5 visits will be as follows: 
• 
Visit 1- Screening visit 
• 
Visit 2- EEC Screening Visit 
• 
Visit 3- Treatment Visit 

CLINICAL STUDY 
PROTOCOL 
   C2D01121/ AM-301-CL-21-02  
                      Altamira Medica AG 
  
 
Cliantha Research    
CONFIDENTIAL 
Page 15 of 58 
     Version: Final 2.0  
Date: 27-SEP-2021 
 
• 
Visit 4- Treatment Visit 
• 
Visit 5- Treatment Visit 
• 
Follow-up telephone call 
 
Study 
Products 
and 
Study 
Sequence 
Study Product: AM-301 Nasal Spray 
Treatment groups will be as follows: 
A: One Spray of AM-301 per nostril 
B: Two Sprays of AM-301 per nostril (with different spray angles) 
C: No treatment 
The study will consist of 6 study sequences: 
• 
Sequence 1 (n = 6): ABC 
• 
Sequence 2 (n = 6): BCA 
• 
Sequence 3 (n = 6): CAB 
• 
Sequence 4 (n = 6): ACB 
• 
Sequence 5 (n = 6): BAC 
• 
Sequence 6 (n = 6): CBA 
Study population 
Approximately 36 males and non-pregnant females, 18-65 years of age inclusive, with a 
History of Perennial Allergic Rhinitis (PAR) due to house dust mites. 
Route of 
Administration 
Intranasal 
Confinement 
Study participants will remain confined to the clinic for approximately  4-5 hours during 
each screening and treatment EEC visits. 
Study Conduct 
The clinical trial will consist of 5 clinic visits; (1 medical screening, 1 EEC screening visit 
3 EEC treatment visits).   
Medical Screening Visit 1 (Day-28 to -1)  
At Visit 1, eligible study participants will first sign the informed consent document, 
complete all screening procedures, including inclusion and exclusion criteria and safety 
labs, and move on to Visit 2 if eligible for EEC screening. 
 
EEC Screening Visit 2 (Day 1) 
At Visit 2, eligible study participants will have a nasal exam performed by the 
Investigator. Study participants will then enter the EEC for a total of 3 hours. Study 
participants will record their symptoms every 20 ± 5 minutes throughout the 3-hour EEC 
session. 
Treatment Visit 3 (Day 8 + 2), Visit 4 (Day 15 + 2) and Visit 5 (Day 22+ 2) 
Eligible study participants will return for Visit 3 after at least 7 days after visit 2. Study 
Participants will be randomized at Visit 3. 
Subsequently study participants will return to the clinic for Visit 4 at least 7 days after 
Visit 3 and for Visit 5 at least 7 days after Visit 4. 
Treatment will occur on site performed by trained clinical staff. Study participants will 
enter the EEC on these visits following administration, but no later than 10 minutes after 

CLINICAL STUDY 
PROTOCOL 
   C2D01121/ AM-301-CL-21-02  
                      Altamira Medica AG 
  
 
Cliantha Research    
CONFIDENTIAL 
Page 16 of 58 
     Version: Final 2.0  
Date: 27-SEP-2021 
 
treatment administration and will record their symptoms every 20 minutes throughout 
the 3-hour EEC session. 
Following the assessments at Visit 5, this will conclude the study. AE’s will also be 
recorded throughout each visit . 
Follow-Up Telephone Call 
Follow-up Telephone call will be done after approximately 7 + 2 days of completion of 
Visit 5. 
The following assessment will be conducted: 
• 
Subjects will be asked for any occurrence of adverse events after last treatment 
administration.  
• 
Subjects will be asked if they have taken any concomitant medications since 
last treatment administration.  
Inclusion Criteria 
1. Study participants must be willing and able to give their signed and dated written 
informed consent to participate in the study prior to commencing any study-related 
activities  
2. Male and female study participants aged 18-65 years at the time of Informed consent 
and medical screening will be included in the study. Women will be considered for 
inclusion if they are 
• 
Not pregnant, as confirmed by pregnancy test at visit 1, not nursing and not 
planning to become pregnant over the duration of the study. 
• 
Of non-child bearing potential (i.e. physiologically incapable of becoming 
pregnant, including any female who is post-menopausal, surgically sterile 
with documented proof of hysterectomy or tubal ligation or bilateral 
oophorectomy or meets clinical criteria for menopause and has been 
amenorrhoeic for more than 1 year prior to the screening visit). 
• 
WOCBP must use effective methods of birth control starting at least 1 month 
prior to the Screening Visit 1 and until 72 hours after the last study 
procedure, such as total abstinence, hormonal or non-hormonal intrauterine 
device, a double-barrier method (Condom and diaphragm/cervical with 
spermicide (foam, cream, gel, sponge)), oral, transdermal, injected or 
implanted hormonal contraceptive. A sterile sexual partner is not considered 
an adequate form of birth control.  
3. Body mass index between 18.0 and 32.0 kg/m2 inclusive. 
4. History of perennial allergic rhinitis to house dust mite for more than 1 year. 
5. Positive Skin Prick Test (SPT) for Dermatophagoides pteronyssinus (der p) allergen 
at screening or within 12 months prior to the screening visit. Test will not be repeated 
if they have been performed at Cliantha Research in previous 12 months.  
6. Spirometry will be performed at Screening. Study participants must have an 
acceptable spirometry assessment showing FEV1 that is ≥80% of the predicted GLI-
2012 value and a Tiffeneau ratio (FEV1/FVC ratio [FEV1%]) of ≥0.7 performed as 
per American Thoracic Society (ATS) standards to be eligible for the study.  
7. Adequate level of rhinitis symptoms in a house dust mite challenge, defined as a 
change in TNSS of at least 4 units over pre-EEC TNSS on at least two time points 
within the 3-hour screening house dust mite challenge (Visit 2). 

CLINICAL STUDY 
PROTOCOL 
   C2D01121/ AM-301-CL-21-02  
                      Altamira Medica AG 
  
 
Cliantha Research    
CONFIDENTIAL 
Page 17 of 58 
     Version: Final 2.0  
Date: 27-SEP-2021 
 
8. Total Nasal Symptom Score (TNSS) of ≤ 4 prior to entering the house dust mite 
chamber at screening EEC Visit 2.  
9. Smokers need to be able to refrain from smoking six hours before the allergen 
challenge during all EEC visits  
10. Agree to abide by the study restrictions and return for the required assessments and 
must be willing to comply with study procedures and study protocol. 
Exclusion Criteria 
 
1. Any clinically relevant abnormal findings in physical examination, clinical chemistry, 
hematology, urinalysis, vital signs, lung function at screening visit, which, in the 
opinion of the investigator, may either put the subject at risk because of participation 
in the study or may influence the results of the study, or the subject’s ability to 
participate in the study. 
2. Use of any medication considered to have an influence on the outcome of the study 
during the EEC session, at the discretion of the Investigator and/or designee. 
3. Recent nasal ulcers, mucosal erosion, nasal surgery, or nasal trauma, that might 
interfere with study results as determined by the Investigator and/or designee. 
4. Past or present concomitant medical conditions, which as judged by the investigator, 
may affect the outcome of this study. These diseases include, but are not limited to, 
cardiovascular disease, malignancy, hepatic disease, renal disease, hematological 
disease, neurological disease, endocrine disease or pulmonary disease (including 
but not confined to chronic bronchitis, emphysema, tuberculosis, bronchiectasis or 
cystic fibrosis). 
5. Allergen-specific Immunotherapy (SIT) within 2 years prior to the study. 
6. Any upper respiratory tract infection (including rhinitis and sinusitis) in the last 14 
days before entering the study Visit 1. 
7. Asthmatics will be excluded from the study.  
8. Conditions or factors, which would make the subject unlikely to be able to stay in the 
EEC for 3 hours. 
9. Any medical condition or concomitant medication that makes the use of adrenalin 
less effective (e.g. use of local and systemic beta-blockers, ACE inhibitors). 
10. Known sensitivity to the constituents of AM-301 like Propylene glycol or Mannitol. 
11. Treatment with antipsychotic medications with antihistaminic effect (e.g. 
chlorpromazine, levomepromazine, clozapine, olanzapine, tioridazine). 
12. Participation in another clinical trial 30 days prior to enrollment.  
13. History of drug or alcohol abuse within the last two years. 
14. Risk of non-compliance with study procedures. 
15. Suspected inability to understand the protocol requirements, instructions and study-
related restrictions, the nature, scope, and possible consequences of the study. 
16. History of an acute infection four weeks prior to Visit 1. 
17. Study participants with severe septum deviation or other structural nasal 
abnormalities that prevent the intranasal administration of a medical device.