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Pro
duct
ion
Pre
-Clinic
al
Clinic
al Tri
al
Dr Setayesh Sadeghi, BCPS
Medical Department Manager at Arta Pharmed
Pro
duct
ion
Pre
-Clinic
al
Clinic
al Tri
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Small, Non-enveloped, Double-stranded DNA virus
Capsid Protein, L1
Papilloguard®
Pro
duct
ion
Pre
-Clinic
al
Clinic
al Tri
al
Papilloguard®
Baculovirus-Insect expression system
Small, Non-enveloped, Double-stranded DNA virus
Trichoplusia ni
Pro
duct
ion
Pre
-Clinic
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Clinic
al Tri
al
Virus-like particles (VLPs) adjuvanted by
MPL and aluminum hydroxide
Small, Non-enveloped, Double-stranded DNA virus
Baculovirus-Insect expression system
Papilloguard®
Pro
duct
ion
Pre
-Clinic
al
Clinic
al Tri
al
0.5 mL Suspension (20 µg L1 HPV16 & L1 HPV18)
Virus-like particles (VLPs) adjuvanted by
MPL and aluminum hydroxide
Small, Non-enveloped, Double-stranded DNA virus
Baculovirus-Insect expression system
Papilloguard®
Pro
duct
ion
Pre
-Clinic
al
Clinic
al Tri
al
GENERAL CHARACTERISTICSNO. PARAMETER TESTED METHOD
1 Appearance Visual observation
2 Mass variation EP 2.9.40
3 pH pH metry EP (2.2.3)
4 extractable volume EP 2.9.17
5 aluminum content EP 2.5.13
6 MPL content Thin Layer Chromatography (TLC)
7
completeness of adsorption to
aluminium component – unbound
MPL
Unbound MPL content by TLC
8
completeness of adsorption to
aluminium component – unbound
HPV-16/18 L1 VLP
Unbound Protein Content by
Lowry
IDENTITY AND PURITY
10 identity (HPV-16 L1 VLP)Indirect ELISA with inhibited
antibody
11 identity (HPV-18 L1 VLP)Indirect ELISA with inhibited
antibody
SAFETY
12 Sterility EP (2.6.1)
ASSAY/ POTENCY
13 Potency ELISA/ in-vivo ED50
Quality Control
Papilloguard®
Pro
duct
ion
Pre
-Clinic
al
Clinic
al Tri
al
NOYAN Biopharma
Papilloguard®
Pro
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ion
Pre
-Clinic
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Clinic
al Tri
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Toxicity Test
❖ No death or any other behavioral or
physical damage
❖ Histopathological observation
Skin Irritation
Test
Not Irritant for skin
Papilloguard®
Pro
duct
ion
Pre
-Clinic
al
Clinic
al Tri
al
Clinical Trial Authorization
1. Protocol
2. CRF
3. PI CV
4. GCP
5. GMP
6. EC
7. IB (Invitro, Preclinical)
8. COI
9. IRCT
10. Contract
Pro
duct
ion
Pre
-Clinic
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Pro
duct
ion
Pre
-Clinic
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Clinic
al Tri
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First CT for Vaccine in Iran
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ion
Pre
-Clinic
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Clinic
al Tri
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Clinical Trial Authorization (CTA)
Papilloguard®
Pro
duct
ion
Pre
-Clinic
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Clinic
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N: 504
Were screened
Eligibility criteria
N: 108 N: 109• All women
• Mean Age: 21.40 ± 2.95 years
•All women
•Mean Age: 21.38 ± 2.97 years
Study StartedN: 218
Were enrolled
0.5 mL vaccine
Papilloguard®
Pro
duct
ion
Pre
-Clinic
al
Clinic
al Tri
al
Day 0 Day 30 Day 90 Day 180 Day 210
Visit 1 Visit 2 Visit 3 Visit 4 Visit 5
Primary Outcome: GMT Ratio
Secondary Outcome: Seroconversion
Papilloguard®
Pro
duct
ion
Pre
-Clinic
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Clinic
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𝐻1:𝐺𝑀𝑇𝑇𝑒𝑠𝑡 (𝑃𝑎𝑝𝑖𝑙𝑙𝑜𝑔𝑢𝑎𝑟𝑑)
𝐺𝑀𝑇𝐶𝑜𝑛𝑡𝑟𝑜𝑙 (𝐶𝑒𝑟𝑣𝑎𝑟𝑖𝑥)> 0.5
Non-Inferiority Margin with accordance to WHO recommendations outlined in section C.2.3.2.
-5
-3
-1
1
3
5
7
9
11
13
15
17
19
21
0 1 2 3 4 5 6 7 8
Rel
ativ
e P
ote
ncy
Month
Lower Limit GMT HPV-16
GMT Cervarix LL GMT Papilloguard LL
-5
-3
-1
1
3
5
7
9
11
13
15
17
19
21
0 1 2 3 4 5 6 7 8
Rel
ativ
e P
ote
ncy
Month
Lower Limit GMT HPV-18
GMT Cervarix LL GMT Papilloguard LL
Primary Outcome (GMT Ratio)Papilloguard®
Pro
duct
ion
Pre
-Clinic
al
Clinic
al Tri
al
Group
HPV 18 HPV 16
Relative Potency
Lower Limit of
Confidence
Interval
Relative Potency
Lower Limit of
Confidence
IntervalGMT Ratio
(Papilloguard
/Cervarix)
0.91 0.93 0.66 0.65
Efficacy Result > 0.5
Primary Outcome (GMT Ratio)
Papilloguard®
Pro
duct
ion
Pre
-Clinic
al
Clinic
al Tri
alHPV 18
Post Injectionn + -
Cervarix 92 91 1Papilloguard 92 92 0
HPV 16Post Injection
n + -Cervarix 92 91 1
Papilloguard 92 89 3
Secondary Outcome (Seroconversion)
Papilloguard®
> 93% Seropositive
Pro
duct
ion
Pre
-Clinic
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Clinic
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Day 0 Day 30 Day 90 Day 180 Day 210
Visit 1 Visit 2 Visit 3 Visit 4 Visit 5
Primary Outcome: GMT
Secondary Outcome: Seroconversion
Safety Outcome
(Solicited & Unsolicited AEs)
Pro
duct
ion
Pre
-Clinic
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Clinic
al Tri
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Cervarix % (n) Papilloguard % (n) PV
Injection 1 2 3 1 2 3 1 2 3
N 108 101 94 109 101 95 - - -
Discomfort
at Injection
Site
72.55 (74)
54.90 (56)
59.95 (56)
78.22 (79)
52.58 (51)
55.32 (52)
0.35 0.74 0.61
Fever11.76 (12)
6.86 (7)
10.53 (10)
9.90 (10)
5.15 (5) 6.38 (6) 0.67 0.61 0.31
Arthralgia9.80 (10)
4.90 (5)
8.42 (8)
4.95 (5)
4.12 (4) 2.13 (2) 0.19 0.79 0.05
Fatigue19.61 (20)
15.69 (16)
12.63 (12)
18.81 (19)
7.22 (7) 5.32 (5) 0.88 0.06 0.08
GI
Symptoms
9.80 (10)
10.78 (11)
9.47 (9)
5.94 (6)
1.03 (1) 5.32 (5) 0.31 0.00 0.28
Headache14.71 (15)
11.76 (12)
13.68 (13)
7.92 (8)
4.12 (4) 3.19 (3) 0.55 0.05 0.01
Myalgia23.53 (24)
15.69 (16)
14.74 (14)
18.81 (19)
6.19 (6) 5.32 (5) 0.41 0.03 0.03
Rash 0.98 (1)0.00 (0)
0.00 (0)
0.00 (0)
1.03 (1) 2.13 (2) 0.32 0.97 0.15
Pimple 0.00 (0)0.00 (0)
0.00 (0)
0.00 (0)
00.00 (0)
1.06 (1) - - 0.13
Solicited Adverse EventsPapilloguard®
TH ANK Y OUFOR Y OUR ATTENTION
Papilloguard®
Special thanks to Dr. Afshani
Medical department supervisor