ATX-GD-59 in Patients With Graves Disease Not Treated With Anti-thyroid Therapy

• Sponsor: Apitope International NV (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02973802
• Collaborator: Quintiles, Inc. (Industry), European Commission (Other)
• Enrollment: 12
• Locations: 8
• Arm: 1
• Actual Duration (Months): 17.4
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Phase 1 study to assess the safety and biological activity of ATX-GD-59 in patients with Graves Disease not currently treated with anti-thyroid therapy. This will be an open label dose titration involving injections on 10 occasions, each two weeks apart. After dosing is complete there will be a 12 week follow up period. Blood samples will be drawn throughout the study to monitor safety and the body's response to the injections. Thyroid function will be measured throughout the trial to monitor Graves disease progression.

Condition or Disease	Intervention/Treatment	Phase
Graves Disease	Biological: ATX-GD-59	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Proof of Principle Study of ATX-GD-59 in Male and Female Subjects With Graves' Disease Not Currently Treated With Anti-thyroid Therapy: An Open Label Study, With an Upward Titration Over Five Dose Levels Administered by Intradermal Injection
• Actual Study Start Date: Sep 1, 2016
• Actual Primary Completion Date: Feb 14, 2018
• Actual Study Completion Date: Feb 14, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ATX-GD-59 treatment An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 will be administered two weeks apart by intradermal injection.	Biological: ATX-GD-59; Disease specific immune modulating treatment for Graves Disease

Outcome Measures

Primary Outcome Measures

1. Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. [22 weeks]

   An adverse event (AE) was defined as any untoward medical occurrence in a subject administered study drug that did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, disease or outcome of death temporally associated with the use of study drug, whether or not considered causally related to the study drug. Treatment emergent adverse events (TEAEs) were any AE that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of study drug. Relationship, as indicated by the Investigator, was classified as 'not related', 'possibly related', 'probably related' or 'definitely related' (increasing severity of relationship). A drug related AE was defined as an AE with a relationship to study drug of 'possibly related', 'probably related' or 'definitely related' or with a missing or unknown relationship to study drug

Secondary Outcome Measures

1. Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by TSHR-binding Inhibitory Immunoglobulin (TBII) [Weeks 18, 22 and 30]

   TSHR-binding inhibitory immunoglobulin (TBII) are autoantibodies directed against the TSH receptor. TBII is used clinically for the differential diagnosis and management of Graves' Disease.

2. Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Stimulatory TSHR Antibodies (TSAb) [Weeks 18, 22 and 30]

   Stimulatory TSHR antibodies (TSAb) assays were measured using cell-based methods described by Leschik et al. TSAb activity is measured by calculating percentage specimen-to-reference ratio (%SRR).

3. Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Blocking TSHR Antibodies (TBAb) [Weeks 18, 22 and 30]

   Blocking TSHR antibodies (TBAb) assays were measured using cell-based methods described by Leschik et al. TBAb activity is measured by calculating percentage inhibition.

4. Change in Serum Free Triiodothyronine (fT3) From Baseline to Week 22. [Weeks 18, 22 and 30]

   Serum fT3 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT3 value at study day 1.

5. Change in Serum Free Thyroxine (T4) From Baseline to Week 22. [Weeks 18, 22 and 30]

   Serum fT4 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.

6. Change in Serum Thyroid Stimulating Hormone (TSH) From Baseline to Week 22. [Weeks 18, 22 and 30]

   Serum TSH was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.

7. Change From Baseline in Peripheral Blood Mononuclear Cell (PBMC) T Cell Activity [weeks 0, 18 and 22]

8. Change From Baseline in IL-10 mRNA Expression in PBMCs [weeks 0, 18 and 22]

9. Change From Baseline in Biomarker Signature of PBMC Cells [weeks 0, 18 and 22]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. A diagnosis of Graves' disease as assessed by a physician from clinical and laboratory findings and not receiving anti-thyroid therapy.

2. Quantifiable levels of TSHR antibodies.

3. Raised levels of free T3 and/or free T4 (not exceeding 15 pmol/L and 35 pmol/L respectively) including undetectable levels of thyroid stimulating hormone.

4. HLA-DRB115, HLA DRB103 and or HLA DRB1*04 positive.

5. Age 18 - 65 years inclusive at the time of informed consent.

6. The subject must be willing and able to give written informed consent and must be willing to comply with protocol assessments/procedures.

7. Male subjects must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control for the duration of the study until at least 90 days after the last dose of ATX-GD-59.

8. Female subjects of child bearing potential must: - neither be pregnant nor breast-feeding, nor attempting to conceive, and - use a highly effective method of contraception as defined below, throughout the entire duration of the study and for at least 90 days after the last dose of ATX-GD-59. A serum pregnancy test will be performed at the screening visit in women of child bearing potential. Thereafter urine pregnancy tests will be performed. A positive result will exclude the woman from the study immediately. A highly effective method of contraception is defined as those which result in a low failure rate when used consistently and correctly such as implants, injectable, combined oral contraceptives, some Intrauterine Devices (IUDs), unless post-menopausal or surgically sterilized. Barrier forms of contraception are considered appropriate when used in combination with one of the above methods.

Exclusion Criteria:

1. Subjects who are pregnant or breastfeeding and/or subjects in the post-partum period.

2. A known history of, or hypersensitivity reactions that in the opinion of the investigator would exclude the subjects' participation in the study.

3. Treatment with any Anti-Thyroid Drugs eg carbimazole within the previous 3 months prior to Study Day 1.

4. Previous treatment with radioiodine or (partial or complete) thyroidectomy.

5. Signs of moderate or severe orbitopathy including optic nerve compression requiring steroids and/or a clinical activity score >3.

6. Large and compressive goitres causing localised symptoms such as difficulty swallowing or breathing.

7. Treatment with steroids (administered via the oral and/or parenteral routes) or adrenocorticotropic hormone with the exception of inhaled steroids within the three months prior to Study Day 1.

8. Symptoms and signs of thyroid storm such as confusion, pyrexia with no other cause than hyperthyroidism.

9. Significant cardiac disease and/or atrial fibrillation that would require urgent treatment of thyrotoxicosis.

10. Prior treatment with biological or peptide-based therapeutics including rituximab.

11. Prior use of disease related T cell vaccine or peptide-tolerising agent to treat Graves' disease.

12. Detectable levels of antibodies in plasma specific for any of the peptides within ATX-GD-59 at the screening visit.

13. A history of significant drug allergies.

14. The use of any investigational drug, or participation in any Clinical Trial within three months prior to Study Day 1.

15. Treatment with any cytokine or anti-cytokine therapy within three months prior to Study Day 1.

16. Inadequate liver function, defined by a total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase > 3 times the upper limit of the normal values at Screening visit. 17. Subject with any significant medical illness or psychiatric condition that in the opinion of the Investigator, would preclude participation in the study or impair the ability to give informed consent; any other clinically apparent autoimmune disease.

17. Clinically significant illness, as determined by the investigator, within 4 weeks prior to the first dose (Study Day 1) of ATX-GD-59.

18. Known history of active or chronic infectious disease or any disease which compromises immune function (e.g. HIV+, HTLV-1, Lyme disease, Latent or active TB, Hepatitis).

19. Major surgery in previous four weeks before screening visit. 21. Known osteoporosis or metabolic bone disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Queen Elizabeth Hospital	Birmingham		United Kingdom
2	University Hospital of Wales	Cardiff		United Kingdom
3	Royal Devon and Exeter Hospital	Exeter		United Kingdom
4	St James's University Hospital	Leeds		United Kingdom	LS9 7TF
5	Hammersmith Hospital	London		United Kingdom	W12 0HS
6	Kings College Hospital	London		United Kingdom
7	The Christie	Manchester		United Kingdom
8	Royal Victoria Infirmary	Newcastle		United Kingdom

Sponsors and Collaborators

• Apitope International NV
• Quintiles, Inc.
• European Commission

Investigators

• Principal Investigator: Simon HS Pearce, Royal Victoria Infirmary

Study Documents (Full-Text)

• Study Protocol - Jan 6, 2017
• Statistical Analysis Plan - Feb 28, 2018

More Information

Publications

None provided.

• Responsible Party: Apitope International NV
• ClinicalTrials.gov Identifier: NCT02973802
• Other Study ID Numbers: ATX-GD-59-001
• First Posted: Nov 25, 2016
• Last Update Posted: Jun 14, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Apitope International NV: Graves Disease; Phase 1
• Additional relevant MeSH terms: Graves Disease

Study Results

Participant Flow

Recruitment Details	This study enrolled patients diagnosed with Graves Disease from 8 hospital clinics located in the UK. The last patient enrolled completed dosing in February 2018.
Pre-assignment Detail	28 subjects were screened for the study, of which 12 were eligible, and commenced treatment with ATX-GD-59.

Arm/Group Title	ATX-GD-59 Treatment
Arm/Group Description	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Period Title: Overall Study
STARTED	12
COMPLETED	10
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	ATX-GD-59 Treatment
Arm/Group Description	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.7 (9.69)
Sex: Female, Male (Count of Participants)
Female	11 91.7%
Male	1 8.3%
Race/Ethnicity, Customized (Count of Participants)
White	11 91.7%
Asian	1 8.3%

Outcome Measures

1. Primary Outcome

Title	Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline.
Description	An adverse event (AE) was defined as any untoward medical occurrence in a subject administered study drug that did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, disease or outcome of death temporally associated with the use of study drug, whether or not considered causally related to the study drug. Treatment emergent adverse events (TEAEs) were any AE that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of study drug. Relationship, as indicated by the Investigator, was classified as 'not related', 'possibly related', 'probably related' or 'definitely related' (increasing severity of relationship). A drug related AE was defined as an AE with a relationship to study drug of 'possibly related', 'probably related' or 'definitely related' or with a missing or unknown relationship to study drug
Time Frame	22 weeks

Outcome Measure Data

Analysis Population Description

The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria. The Safety population was denoted as the 'Intention-to-treat population' for the summarisation of safety endpoints.

Arm/Group Title	ATX-GD-59 Treatment
Arm/Group Description	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Measure Participants	12
Total Adverse Events	311
Mild Adverse Events	293
Moderate Adverse Events	18
Severe Adverse Events	0
Drug Related Adverse Events	180
Total Serious Adverse Events	3
Drug Related Serious Events	1
Adverse Events leading to death	0
Adverse Events leading to early study withdrawal	0
Events leading to dose interruption or suspension	0
Treatment emergent injection related reaction	153

2. Secondary Outcome

Title	Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by TSHR-binding Inhibitory Immunoglobulin (TBII)
Description	TSHR-binding inhibitory immunoglobulin (TBII) are autoantibodies directed against the TSH receptor. TBII is used clinically for the differential diagnosis and management of Graves' Disease.
Time Frame	Weeks 18, 22 and 30

Outcome Measure Data

Analysis Population Description

The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.

Arm/Group Title	ATX-GD-59 Treatment
Arm/Group Description	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Measure Participants	12
Change from baseline at week 18	-0.7737 (1.55475)
Change from baseline at week 22	-0.6602 (1.35220)
Change from baseline at week 30	-0.8971 (1.67639)

3. Secondary Outcome

Title	Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Stimulatory TSHR Antibodies (TSAb)
Description	Stimulatory TSHR antibodies (TSAb) assays were measured using cell-based methods described by Leschik et al. TSAb activity is measured by calculating percentage specimen-to-reference ratio (%SRR).
Time Frame	Weeks 18, 22 and 30

Outcome Measure Data

Analysis Population Description

The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.

Arm/Group Title	ATX-GD-59 Treatment
Arm/Group Description	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Measure Participants	12
Change from baseline at week 18	-92.7 (145.73)
Change from baseline at week 22	-54.0 (118.94)
Change from baseline at week 30	-39.3 (125.36)

4. Secondary Outcome

Title	Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Blocking TSHR Antibodies (TBAb)
Description	Blocking TSHR antibodies (TBAb) assays were measured using cell-based methods described by Leschik et al. TBAb activity is measured by calculating percentage inhibition.
Time Frame	Weeks 18, 22 and 30

Outcome Measure Data

Analysis Population Description

The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.

Arm/Group Title	ATX-GD-59 Treatment
Arm/Group Description	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Measure Participants	12
Change from baseline at week 18	12.9 (46.50)
Change from baseline at week 22	7.0 (55.54)
Change from baseline at week 30	-0.1 (60.49)

5. Secondary Outcome

Title	Change in Serum Free Triiodothyronine (fT3) From Baseline to Week 22.
Description	Serum fT3 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT3 value at study day 1.
Time Frame	Weeks 18, 22 and 30

Outcome Measure Data

Analysis Population Description

The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.

Arm/Group Title	ATX-GD-59 Treatment
Arm/Group Description	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Measure Participants	12
Change from baseline at week 18	-11.75 (26.513)
Change from baseline at week 22	-14.19 (25.549)
Change from baseline at week 30	-15.79 (27.367)

6. Secondary Outcome

Title	Change in Serum Free Thyroxine (T4) From Baseline to Week 22.
Description	Serum fT4 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.
Time Frame	Weeks 18, 22 and 30

Outcome Measure Data

Analysis Population Description

The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.

Arm/Group Title	ATX-GD-59 Treatment
Arm/Group Description	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Measure Participants	12
Change from baseline at week 18	-9.80 (24.622)
Change from baseline at week 22	-14.54 (20.011)
Change from baseline at week 30	-9.24 (27.368)

7. Secondary Outcome

Title	Change in Serum Thyroid Stimulating Hormone (TSH) From Baseline to Week 22.
Description	Serum TSH was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.
Time Frame	Weeks 18, 22 and 30

Outcome Measure Data

Analysis Population Description

The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol

Arm/Group Title	ATX-GD-59 Treatment
Arm/Group Description	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Measure Participants	12
Change from baseline at week 18	0.267 (0.8028)
Change from baseline at week 22	0.309 (0.8398)
Change from baseline at week 30	0.473 (1.1915)

8. Secondary Outcome

Title	Change From Baseline in Peripheral Blood Mononuclear Cell (PBMC) T Cell Activity
Time Frame	weeks 0, 18 and 22

Outcome Measure Data

Analysis Population Description

No clear treatment effects could be determined possibly due to technical issues with the preparation and assay of the PBMCs. In addition, the 2 week post dose time point of blood sampling, meant that the induced Treg cells or cytokine changes were no longer detectable in peripheral blood.

Arm/Group Title	ATX-GD-59 Treatment
Arm/Group Description	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Measure Participants	0

9. Secondary Outcome

Title	Change From Baseline in IL-10 mRNA Expression in PBMCs
Time Frame	weeks 0, 18 and 22

Outcome Measure Data

Analysis Population Description

No clear treatment effects could be determined possibly due to technical issues with the preparation and assay of the PBMCs. In addition, the 2 week post dose time point of blood sampling, meant that the induced Treg cells or cytokine changes were no longer detectable in peripheral blood.

Arm/Group Title	ATX-GD-59 Treatment
Arm/Group Description	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Measure Participants	0

10. Secondary Outcome

Title	Change From Baseline in Biomarker Signature of PBMC Cells
Time Frame	weeks 0, 18 and 22

Outcome Measure Data

Analysis Population Description

No clear treatment effects could be determined possibly due to technical issues with the preparation and assay of the PBMCs. In addition, the 2 week post dose time point of blood sampling, meant that the induced Treg cells or cytokine changes were no longer detectable in peripheral blood.

Arm/Group Title	ATX-GD-59 Treatment
Arm/Group Description	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection. ATX-GD-59: Disease specific immune modulating treatment for Graves Disease
Measure Participants	0

Adverse Events

Time Frame	Adverse events were recorded from screening through to the final follow up visit at week 30.
Adverse Event Reporting Description	Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.
Arm/Group Title	Treatment Emergent Adverse Events		Non Treatment Emergent Adverse Events
Arm/Group Description	Treatment emergent adverse events were any adverse events that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of ATX-GD-59		Any non-treatment emergent adverse events.
All Cause Mortality
	Treatment Emergent Adverse Events		Non Treatment Emergent Adverse Events
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Treatment Emergent Adverse Events		Non Treatment Emergent Adverse Events
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		0/12 (0%)
Cardiac disorders
Paroxysmal Atrial Fibrillationion	1/12 (8.3%)	1	0/12 (0%)	0
Gastrointestinal disorders
Mild Nausea	1/12 (8.3%)	1	0/12 (0%)	0
Vomiting	1/12 (8.3%)	1	0/12 (0%)	0
General disorders
Non-Cardiac Chest Pain	1/12 (8.3%)	1	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	Treatment Emergent Adverse Events		Non Treatment Emergent Adverse Events
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		4/12 (33.3%)
Cardiac disorders
Palpitations	2/12 (16.7%)	2	1/12 (8.3%)	1
Angina pectoris	1/12 (8.3%)	1	0/12 (0%)	0
Atrial fibulation	1/12 (8.3%)	1	0/12 (0%)	0
Atrioventricular block first degree	1/12 (8.3%)	1	0/12 (0%)	0
Tachycardia	1/12 (8.3%)	4	0/12 (0%)	0
Eye disorders
Eyelid oedema	1/12 (8.3%)	1	0/12 (0%)	0
Ocular hyperaemia	1/12 (8.3%)	1	0/12 (0%)	0
Gastrointestinal disorders
Diarrhoea	3/12 (25%)	4	0/12 (0%)	0
Vomiting	3/12 (25%)	10	0/12 (0%)	0
Nausea	2/12 (16.7%)	13	0/12 (0%)	0
Abdominal pain lower	1/12 (8.3%)	1	0/12 (0%)	0
Abdominal tenderness	1/12 (8.3%)	2	0/12 (0%)	0
Haematochezia	1/12 (8.3%)	1	0/12 (0%)	0
Toothache	1/12 (8.3%)	1	0/12 (0%)	0
General disorders
Injection site erythema	10/12 (83.3%)	61	0/12 (0%)	0
Injection site swelling	8/12 (66.7%)	46	0/12 (0%)	0
Injection site pain	6/12 (50%)	27	0/12 (0%)	0
Injection site pruritus	3/12 (25%)	7	0/12 (0%)	0
Injection site rash	2/12 (16.7%)	2	0/12 (0%)	0
Injection site urticaria	2/12 (16.7%)	9	0/12 (0%)	0
Pyrexia	2/12 (16.7%)	12	0/12 (0%)	0
Asthenia	1/12 (8.3%)	1	0/12 (0%)	0
Fatigue	1/12 (8.3%)	1	0/12 (0%)	0
Feeling hot	1/12 (8.3%)	3	0/12 (0%)	0
Injection site discomfort	1/12 (8.3%)	1	0/12 (0%)	0
Malaise	1/12 (8.3%)	2	0/12 (0%)	0
Non-cardiac chest pain	1/12 (8.3%)	9	0/12 (0%)	0
Oedema	1/12 (8.3%)	1	0/12 (0%)	0
Peripheral swelling	1/12 (8.3%)	1	0/12 (0%)	0
Suprapubic Pain	1/12 (8.3%)	1	0/12 (0%)	0
Thirst	1/12 (8.3%)	1	0/12 (0%)	0
Hepatobiliary disorders
Hepatic steatosis	1/12 (8.3%)	1	0/12 (0%)	0
Immune system disorders
Seasonal allergy	1/12 (8.3%)	1	0/12 (0%)	0
Infections and infestations
Urinary tract infection	2/12 (16.7%)	2	1/12 (8.3%)	1
Nasopharyngitis	1/12 (8.3%)	1	1/12 (8.3%)	1
Onychomycosis	1/12 (8.3%)	1	0/12 (0%)	0
Oral herpes	1/12 (8.3%)	1	0/12 (0%)	0
Rhinitis	1/12 (8.3%)	2	0/12 (0%)	0
Upper respiratory tract infection	1/12 (8.3%)	1	1/12 (8.3%)	1
Urinary tract infection bacterial	1/12 (8.3%)	1	0/12 (0%)	0
Vulvovaginal candidiasis	1/12 (8.3%)	1	0/12 (0%)	0
Injury, poisoning and procedural complications
Injection related reaction	1/12 (8.3%)	1	0/12 (0%)	0
Procedural pain	1/12 (8.3%)	1	0/12 (0%)	0
Wrist fracture	1/12 (8.3%)	1	0/12 (0%)	0
Investigations
Blood uric acid increased	1/12 (8.3%)	1	0/12 (0%)	0
Eosinophil count increased	1/12 (8.3%)	1	0/12 (0%)	0
Lymph node palpable	1/12 (8.3%)	1	0/12 (0%)	0
Respiratory rate increased	1/12 (8.3%)	1	0/12 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	1/12 (8.3%)	1	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/12 (16.7%)	2	0/12 (0%)	0
Back pain	2/12 (16.7%)	2	0/12 (0%)	0
Myalgia	2/12 (16.7%)	2	0/12 (0%)	0
Bone pain	1/12 (8.3%)	1	0/12 (0%)	0
Muscle twitching	1/12 (8.3%)	1	0/12 (0%)	0
Musculoskeletal pain	1/12 (8.3%)	2	0/12 (0%)	0
Osteoporosis	1/12 (8.3%)	1	0/12 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of skin	1/12 (8.3%)	1	0/12 (0%)	0
Nervous system disorders
Dizziness	4/12 (33.3%)	19	0/12 (0%)	0
Headache	3/12 (25%)	10	0/12 (0%)	0
Dysgeusia	1/12 (8.3%)	1	0/12 (0%)	0
Migraine	1/12 (8.3%)	1	0/12 (0%)	0
Paraesthesia	1/12 (8.3%)	1	0/12 (0%)	0
Possible Loss of Consciousness	0/12 (0%)	0	1/12 (8.3%)	1
Psychiatric disorders
Anxiety	1/12 (8.3%)	1	0/12 (0%)	0
Depression	1/12 (8.3%)	1	0/12 (0%)	0
Renal and urinary disorders
Dysuria	1/12 (8.3%)	1	0/12 (0%)	0
Reproductive system and breast disorders
Pelvic discomfort	1/12 (8.3%)	1	0/12 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	4/12 (33.3%)	7	1/12 (8.3%)	1
Oropharyngeal pain	3/12 (25%)	4	2/12 (16.7%)	2
Dyspnoea	1/12 (8.3%)	4	0/12 (0%)	0
Pleuritic pain	1/12 (8.3%)	1	0/12 (0%)	0
Productive cough	1/12 (8.3%)	2	0/12 (0%)	0
Throat irritation	1/12 (8.3%)	1	0/12 (0%)	0
Throat tightness	1/12 (8.3%)	1	0/12 (0%)	0
Increased bronchial secretion	0/12 (0%)	0	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
Dermal cyst	1/12 (8.3%)	1	0/12 (0%)	0
Erythema	1/12 (8.3%)	2	0/12 (0%)	0
Rash	1/12 (8.3%)	1	0/12 (0%)	0
Vascular disorders
Hot flush	1/12 (8.3%)	1	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.