Trial Outcomes & Findings for Safety and Immunogenicity of a Cell Derived Subunit Trivalent Nonadjuvanted Influenza Study Vaccine in Adults Aged 18 Years and Above (NCT NCT01880697)

NCT ID: NCT01880697

Last Updated: 2017-02-23

Results Overview

Immunogenicity was assessed in terms of percentages of subjects in both age groups with SRH areas ≥25mm2 against each of the three vaccine strains, three weeks after receiving one dose of TIVc. The related European (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm2 is \>70% for adults aged 18 to ≤60 years and \>60% for subjects aged ≥61 years.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 126 participants
• Primary outcome timeframe: Day 22 (vaccination is on day 1)
• Results posted on: 2017-02-23

Participant Flow

Participant milestones

Measure	TIVc (≥18 to ≤ 60 Years) Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	TIVc (≥ 61 Years) Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere
Overall Study STARTED	63	63
Overall Study COMPLETED	63	62
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Immunogenicity of a Cell Derived Subunit Trivalent Nonadjuvanted Influenza Study Vaccine in Adults Aged 18 Years and Above

Baseline characteristics by cohort

Measure	TIVc (≥18 to ≤ 60 Years) n=63 Participants Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	TIVc (≥ 61 Years) n=63 Participants Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	Total n=126 Participants Total of all reporting groups
Age, Continuous	39.3 years STANDARD_DEVIATION 10.7 • n=5 Participants	68.3 years STANDARD_DEVIATION 4.8 • n=7 Participants	53.8 years STANDARD_DEVIATION 16.7 • n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	33 Participants n=7 Participants	71 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	30 Participants n=7 Participants	55 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 22 (vaccination is on day 1)

Population: Analysis was done on the per-protocol population i.e all subjects who have received study vaccination and provided immunogenicity data both at baseline and after vaccination; did not withdraw informed consent and did not have RT-PCR confirmed influenza during the study.

Immunogenicity was assessed in terms of percentages of subjects in both age groups with SRH areas ≥25mm2 against each of the three vaccine strains, three weeks after receiving one dose of TIVc.

The related European (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm2 is >70% for adults aged 18 to ≤60 years and >60% for subjects aged ≥61 years.

Outcome measures

Measure	TIVc (≥18 to ≤ 60 Years) n=62 Participants Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	TIVc (≥ 61 Years) n=61 Participants Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere
Percentage of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc Day 1/baseline (H1N1 strain)	66 Percentages of Subjects Interval 53.0 to 78.0	41 Percentages of Subjects Interval 29.0 to 54.0
Percentage of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc Day 22 (H1N1 strain)	98 Percentages of Subjects Interval 91.0 to 100.0	84 Percentages of Subjects Interval 72.0 to 92.0
Percentage of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc Day 1/baseline (H3N2 strain)	44 Percentages of Subjects Interval 31.0 to 57.0	39 Percentages of Subjects Interval 27.0 to 53.0
Percentage of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc Day 22 (H3N2 strain)	92 Percentages of Subjects Interval 82.0 to 97.0	77 Percentages of Subjects Interval 65.0 to 87.0
Percentage of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc Day 1/baseline (B strain)	68 Percentages of Subjects Interval 55.0 to 79.0	77 Percentages of Subjects Interval 65.0 to 87.0
Percentage of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc Day 22 (B strain)	98 Percentages of Subjects Interval 91.0 to 100.0	98 Percentages of Subjects Interval 91.0 to 100.0

PRIMARY outcome

Timeframe: Day 22 (vaccination is on day 1)

Population: Analysis was done on the per-protocol population.

Immunogenicity was assessed in terms of percentages of subjects in both age groups achieving seroconversion or significant increase by SRH area against each of the three vaccine strains ,three weeks after receiving one dose of TIVc.

Seroconversion is defined as percentage of subjects with a pre-vaccination SRH area ≤4mm2 achieving a post-vaccination SRH area ≥25 mm2. Significant increase is defined as percentage of subjects with a pre-vaccination SRH area >4mm2 achieving at least 50% increase in post-vaccination SRH area.

The related European (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving post vaccination SRH areas ≥ 25mm2 is >40% for adults aged 18 to ≤60 years and >30% for subjects aged ≥61 years.

Outcome measures

Measure	TIVc (≥18 to ≤ 60 Years) n=62 Participants Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	TIVc (≥ 61 Years) n=61 Participants Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere
Percentages of Subjects With Seroconversion or Significant Increase in SRH Area, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc H1N1	68 Percentages of Subjects Interval 55.0 to 79.0	56 Percentages of Subjects Interval 42.0 to 68.0
Percentages of Subjects With Seroconversion or Significant Increase in SRH Area, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc H3N2	65 Percentages of Subjects Interval 51.0 to 76.0	46 Percentages of Subjects Interval 33.0 to 59.0
Percentages of Subjects With Seroconversion or Significant Increase in SRH Area, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc B	58 Percentages of Subjects Interval 45.0 to 70.0	39 Percentages of Subjects Interval 27.0 to 53.0

PRIMARY outcome

Timeframe: Day 22/day 1

Population: Analysis was done on the per-protocol population.

The antibody responses were evaluated in terms of GMRs of post vaccination GMAs to pre vaccination GMAs against each of the three vaccine strains, three weeks after receiving one dose of TIVc The related European (CHMP) criterion for the assessment of immunogenicity is met if the GMR day 22/day 1 is >2.5 for adults aged 18 to ≤60 years and > 2.0 in for subjects aged ≥61 years.

Outcome measures

Measure	TIVc (≥18 to ≤ 60 Years) n=62 Participants Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	TIVc (≥ 61 Years) n=61 Participants Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere
Geometric Mean Ratio of Post Vaccination Versus Pre Vaccination Geometric Mean Areas (GMAs), After One Dose of TIVc H1N1	2.89 Ratio Interval 2.16 to 3.86	3.14 Ratio Interval 2.29 to 4.31
Geometric Mean Ratio of Post Vaccination Versus Pre Vaccination Geometric Mean Areas (GMAs), After One Dose of TIVc H3N2	2.52 Ratio Interval 2.03 to 3.12	2.05 Ratio Interval 1.67 to 2.53
Geometric Mean Ratio of Post Vaccination Versus Pre Vaccination Geometric Mean Areas (GMAs), After One Dose of TIVc B	1.82 Ratio Interval 1.54 to 2.16	1.5 Ratio Interval 1.28 to 1.76

PRIMARY outcome

Timeframe: Day 22 (vaccination is on day 1)

Population: Analysis was done on the per-protocol population.

Immunogenicity was assessed in terms of percentages of subjects in both age groups with HI titers ≥40, against each of the three vaccine strains, three weeks after receiving one dose of TIVc.

The related European (CHMP) criterion for the assessment of immunogenicity is met if the percentage of subjects achieving HI titers ≥ 40 is >70% for adults aged 18 to ≤60 years and >60% for subjects aged ≥61 years.

Outcome measures

Measure	TIVc (≥18 to ≤ 60 Years) n=62 Participants Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	TIVc (≥ 61 Years) n=61 Participants Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere
Percentage of Subjects With Haemagglutination Inhibition (HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc Day 1/baseline (H1N1 strain)	68 Percentages of Subjects Interval 55.0 to 79.0	66 Percentages of Subjects Interval 52.0 to 77.0
Percentage of Subjects With Haemagglutination Inhibition (HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc Day 22 (H1N1 strain)	100 Percentages of Subjects Interval 94.0 to 100.0	97 Percentages of Subjects Interval 89.0 to 100.0
Percentage of Subjects With Haemagglutination Inhibition (HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc Day 1/baseline (H3N2 strain)	89 Percentages of Subjects Interval 78.0 to 95.0	87 Percentages of Subjects Interval 76.0 to 94.0
Percentage of Subjects With Haemagglutination Inhibition (HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc Day 22 (H3N2 strain)	97 Percentages of Subjects Interval 89.0 to 100.0	95 Percentages of Subjects Interval 86.0 to 99.0
Percentage of Subjects With Haemagglutination Inhibition (HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc Day 1/baseline (B strain)	58 Percentages of Subjects Interval 45.0 to 70.0	46 Percentages of Subjects Interval 33.0 to 59.0
Percentage of Subjects With Haemagglutination Inhibition (HI) Titers ≥40, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc Day 22 (B strain)	94 Percentages of Subjects Interval 84.0 to 98.0	80 Percentages of Subjects Interval 68.0 to 89.0

PRIMARY outcome

Timeframe: Day 22 (vaccination is on day 1)

Population: Analysis was done on the per-protocol population.

Immunogenicity was assessed in terms of percentages of subjects in both age groups achieving seroconversion or significant increase in HI antibody titers after receiving one dose of TIVc.

Seroconversion is defined as percentage of subjects with a pre-vaccination HI titer <10 to a post-vaccination titer ≥40. Significant increase is defined as percentage of subjects with a pre-vaccination HI titer >10 to at least a 4-fold increase in post-vaccination HI antibody titers.

The related European (CHMP) criterion for the assessment of immunogenicity is met if >40 % for adults aged 18 to ≤60 years and >30% for subjects aged ≥61 years achieve seroconversion or significant increase in post-vaccination HI titers.

Outcome measures

Measure	TIVc (≥18 to ≤ 60 Years) n=62 Participants Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	TIVc (≥ 61 Years) n=61 Participants Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere
Percentages of Subjects With Seroconversion or Significant Increase in HI Antibody Titers After Receiving One Dose of TIVc H1N1	63 Percentages of Subjects Interval 50.0 to 75.0	43 Percentages of Subjects Interval 30.0 to 56.0
Percentages of Subjects With Seroconversion or Significant Increase in HI Antibody Titers After Receiving One Dose of TIVc H3N2	47 Percentages of Subjects Interval 34.0 to 60.0	26 Percentages of Subjects Interval 16.0 to 39.0
Percentages of Subjects With Seroconversion or Significant Increase in HI Antibody Titers After Receiving One Dose of TIVc B	48 Percentages of Subjects Interval 35.0 to 61.0	28 Percentages of Subjects Interval 17.0 to 41.0

PRIMARY outcome

Timeframe: Day 22/day 1

Population: Analysis was done on the per-protocol population.

The antibody responses following one dose of TIVc were evaluated in terms of GMRs of post vaccination against pre vaccination geometric mean HI titers against each of the three vaccine strains, three weeks after receiving one dose of TIVc.

The related European (CHMP) criterion for the assessment of immunogenicity is met if the GMR day 22/day 1 is >2.5 for adults aged 18 to ≤60 years and > 2.0 for subjects aged ≥61 years.

Outcome measures

Measure	TIVc (≥18 to ≤ 60 Years) n=62 Participants Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	TIVc (≥ 61 Years) n=61 Participants Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere
Geometric Mean Ratio of Post Vaccination Versus Pre Vaccination HI Antibody Titers, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc H1N1	8.8 Ratio Interval 5.66 to 14.0	3.61 Ratio Interval 2.61 to 5.01
Geometric Mean Ratio of Post Vaccination Versus Pre Vaccination HI Antibody Titers, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc H3N2	3.52 Ratio Interval 2.4 to 5.15	2.22 Ratio Interval 1.63 to 3.01
Geometric Mean Ratio of Post Vaccination Versus Pre Vaccination HI Antibody Titers, Against Each of Three Vaccine Strains After Receiving One Dose of TIVc B	3.31 Ratio Interval 2.45 to 4.47	2.4 Ratio Interval 1.81 to 3.17

PRIMARY outcome

Timeframe: Day 1 to Day 4 post-vaccination

Population: Analysis was done on the solicited safety set population i.e all subjects who have post-vaccination AE or reactogenicity records.

The number of adult and elderly subjects reporting solicited local and systemic adverse events and other solicited adverse events after receiving one dose of TIVc are reported.

Outcome measures

Measure	TIVc (≥18 to ≤ 60 Years) n=63 Participants Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	TIVc (≥ 61 Years) n=63 Participants Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Any local	32 Subjects	18 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Injection site induration	5 Subjects	1 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Injection site erythema	1 Subjects	1 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Injection site ecchymosis	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Injection site pain	31 Subjects	18 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Any systemic	17 Subjects	8 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Chills/shivering	1 Subjects	1 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Malaise	3 Subjects	2 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Myalgia	1 Subjects	1 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Arthralgia	3 Subjects	3 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Headache	11 Subjects	6 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Fatigue	10 Subjects	2 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Fever	1 Subjects	0 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Prophylactic use of analgesics/antipyretics	2 Subjects	0 Subjects
Number of Subjects Reporting Solicited Adverse Events After Receiving One Dose of TIVc Therapeutic use of analgesics/antipyretics	2 Subjects	1 Subjects

PRIMARY outcome

Timeframe: Day 1 through Day 22 post-vaccination

Population: Analysis was done on the unsolicited safety set population i.e all subjects who have post-vaccination AE or reactogenicity records.

The number of subjects in both age groups reporting any unsolicited AEs (between Day 1 to 4), serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal (throughout the study period), after receiving one dose of TIVc is reported.

Outcome measures

Measure	TIVc (≥18 to ≤ 60 Years) n=63 Participants Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	TIVc (≥ 61 Years) n=63 Participants Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc Any AEs	6 Subjects	4 Subjects
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc At least possibly related AEs	2 Subjects	0 Subjects
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc Serious AEs	1 Subjects	0 Subjects
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc At least possibly related SAEs	0 Subjects	0 Subjects
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc Medically attended AEs	4 Subjects	3 Subjects
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc AEs leading to discontinuation	0 Subjects	0 Subjects
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc Death	0 Subjects	0 Subjects

Adverse Events

TIVc (≥18 to ≤ 60 Years)

Serious events: 1 serious events

Other events: 36 other events

Deaths: 0 deaths

TIVc (≥ 61 Years)

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	TIVc (≥18 to ≤ 60 Years) n=63 participants at risk Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	TIVc (≥ 61 Years) n=63 participants at risk Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere
Infections and infestations Tooth infection	1.6% 1/63 • All solicited AEs and unsolicited AEs collected from Day 1 to Day 4; serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal collected from Day 1 to Day 22.	0.00% 0/63 • All solicited AEs and unsolicited AEs collected from Day 1 to Day 4; serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal collected from Day 1 to Day 22.

Other adverse events

Measure	TIVc (≥18 to ≤ 60 Years) n=63 participants at risk Adult subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere	TIVc (≥ 61 Years) n=63 participants at risk Elderly subjects received one dose of the cell-derived trivalent, surface antigen inactivated subunit influenza virus vaccine (TIVc) formulation 2013/2014 Northern Hemisphere
Nervous system disorders Headache	17.5% 11/63 • All solicited AEs and unsolicited AEs collected from Day 1 to Day 4; serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal collected from Day 1 to Day 22.	9.5% 6/63 • All solicited AEs and unsolicited AEs collected from Day 1 to Day 4; serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal collected from Day 1 to Day 22.
General disorders Fatigue	15.9% 10/63 • All solicited AEs and unsolicited AEs collected from Day 1 to Day 4; serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal collected from Day 1 to Day 22.	3.2% 2/63 • All solicited AEs and unsolicited AEs collected from Day 1 to Day 4; serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal collected from Day 1 to Day 22.
General disorders Injection site induration	6.3% 4/63 • All solicited AEs and unsolicited AEs collected from Day 1 to Day 4; serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal collected from Day 1 to Day 22.	1.6% 1/63 • All solicited AEs and unsolicited AEs collected from Day 1 to Day 4; serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal collected from Day 1 to Day 22.
General disorders Injection site pain	50.8% 32/63 • All solicited AEs and unsolicited AEs collected from Day 1 to Day 4; serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal collected from Day 1 to Day 22.	28.6% 18/63 • All solicited AEs and unsolicited AEs collected from Day 1 to Day 4; serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal collected from Day 1 to Day 22.

Additional Information

Posting Director

Novartis Vaccines and Diagnostics

Email: RegistryContactVaccinesUS@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60