Medical Department Manager at Arta Pharmed

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Dr Setayesh Sadeghi, BCPS

Medical Department Manager at Arta Pharmed

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Small, Non-enveloped, Double-stranded DNA virus

Capsid Protein, L1

Papilloguard®

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Papilloguard®

Baculovirus-Insect expression system

Small, Non-enveloped, Double-stranded DNA virus

Trichoplusia ni

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Virus-like particles (VLPs) adjuvanted by

MPL and aluminum hydroxide

Small, Non-enveloped, Double-stranded DNA virus

Baculovirus-Insect expression system

Papilloguard®

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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

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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

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NOYAN Biopharma

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Toxicity Test

❖ No death or any other behavioral or

physical damage

❖ Histopathological observation

Skin Irritation

Test

Not Irritant for skin

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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

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First CT for Vaccine in Iran

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Clinical Trial Authorization (CTA)

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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

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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 Ratio

Secondary Outcome: Seroconversion

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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

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5

7

9

11

13

15

17

19

21

0 1 2 3 4 5 6 7 8

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Lower Limit GMT HPV-16

GMT Cervarix LL GMT Papilloguard LL

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1

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7

9

11

13

15

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19

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0 1 2 3 4 5 6 7 8

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Lower Limit GMT HPV-18

GMT Cervarix LL GMT Papilloguard LL

Primary Outcome (GMT Ratio)Papilloguard®

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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)

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Post Injectionn + -

Cervarix 92 91 1Papilloguard 92 92 0

HPV 16Post Injection

n + -Cervarix 92 91 1

Papilloguard 92 89 3

Secondary Outcome (Seroconversion)

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> 93% Seropositive

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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)

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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