Growth Hormone (GH) DeficiencyGeNeSISNCT01088412

Observational Study of Somatropin Treatment in Children

An observational study of Growth Hormone (GH) Deficiency and Short Stature Homeobox Containing Gene (SHOX) Deficiency, run by Eli Lilly and Company.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

GeNeSIS is an open-label, multinational, multicenter, observational study to evaluate the safety and effectiveness of Humatrope treatment. GeNeSIS is a modular program that includes: Core study: Evaluating the safety and effectiveness of Humatrope in the observational setting Genetic Analysis Sub-study: Investigating… Read more about this study

Who is it for?: Ages 1 day and older
Conditions the study is for: Growth Hormone (GH) Deficiency, Short Stature Homeobox Containing Gene (SHOX) Deficiency, SHOX Deficiency-related Disorder
What is being tested?: Somatropin (recombinant deoxyribonucleic acid [rDNA] origin)
How many people: 22,845 participants
Where: No sites listed yet
Study dates: Apr 1999to Sep 2015
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 day and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Study population: Clinics and private practices

Who may be able to join

All participants participating in GeNeSIS must be enrolled in the core study. Participants for whom written consent to release information is provided may enter the core study if they meet any of the following inclusion guidelines:
Treatment with Humatrope for improvement of growth.
No treatment with somatropin in participants with a history of neoplasia or in those with any SHOX deficiency-related disorder.

Who cannot join

Participants with closed epiphyses are not eligible for GeNeSIS entry. However, participants may remain in the study if epiphyseal closure occurs during study participation.

About this study

Official title: The Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS)

GeNeSIS is an open-label, multinational, multicenter, observational study to evaluate the safety and effectiveness of Humatrope treatment.

GeNeSIS is a modular program that includes:

Core study: Evaluating the safety and effectiveness of Humatrope in the observational setting
Genetic Analysis Sub-study: Investigating the genetic defects underlying growth hormone (GH) deficiency and non-GH-deficient growth disorders
Growth Prediction Sub-study: Working to validate and refine specific models to accurately predict growth response to GH
Short Stature Homeobox containing gene (SHOX) Deficiency Sub-study: Elucidating the clinical, endocrine and radiological features of participants with SHOX deficiency due to loss of, or mutation in the SHOX gene (including participants with Turner syndrome)
Neoplasia Sub-study: To characterize the natural history of neoplastic disease, especially in relation to recurrence/progression of primary neoplasia or development of secondary neoplasia in children with a history of neoplasia

Conditions: Growth Hormone (GH) Deficiency, Short Stature Homeobox Containing Gene (SHOX) Deficiency, SHOX Deficiency-related Disorder, Non-GH-deficient Growth Disorders
Being tested: Somatropin (recombinant deoxyribonucleic acid [rDNA] origin)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Somatropin (recombinant deoxyribonucleic acid [rDNA] origin)Drug
Also called Humatrope, LY137998
Dose, frequency and duration at discretion of attending physician.

Study groups in NCT01088412
Study group	Role	What they receive
Treated		Participants treated with somatropin for improvement of growth Receives: Drug: Somatropin (recombinant deoxyribonucleic acid [rDNA] origin)
Untreated		Untreated participants with presence or history of neoplastic disease evaluated for endocrine or growth disorder or with any SHOX deficiency related disorder

What is being measured

The primary outcome is the main question the study is designed to answer.

Type 2 Diabetes Mellitus in GH-treated Participants
Measured: Year 15
Primary Malignancies in Participant Without Previous Cancer History
Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated.
Measured: Year 15
Final Height (FH) Gain by Diagnostic Group
The standard deviation score (SDS) reports the number of standard deviations from the mean for age and sex for an individual measurement (normal range is -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated.
Measured: Baseline through Year 15

Secondary outcomes (6)

Percentage of Participants With Defects in Genes Associated With Pituitary Development
Percentage of participants with genetic defects associated with pituitary development. Genes included but were not limited to GH1, Growth hormone releasing hormone receptor (GHRHR), Homeobox gene expressed in embryonic stem cells (HESX1), LIM homeobox 3 (LHX3), POU domain, class 1, transcription factor 1 (POU1F1), and Prophet of Pit1 (PROP1).
Measured: Baseline through Year 15
Predicted First Year Height Gain Versus Actual First Year Height Gain
The value for predicted and observed is of limited bearing, it is how each participant's predicted versus observed height gain compare and this is best estimated by the R-squared. An estimation parameter would not be a correct format for the R2 data. R2 can take value between 0 and 1 with values closer to 0 representing a poor fit while values closer to 1 representing a perfect fit
Measured: Baseline through Year 15
Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency
Measured: Baseline, Year 15
Percentage of Participants With Recurrent Neoplasms and Second Neoplasms in Childhood Cancer Survivors
Percentage of participants with recurrence/progression of primary neoplastic disease and/or development of secondary neoplasms in childhood cancer survivors.
Measured: Baseline through Year 15
Percentage of Participants With De Novo Neoplasms
Percentage of participants with the development of de novo neoplastic disease with no history of prior neoplasia.
Measured: Baseline through Year 15
Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses
Measured: Baseline through Year 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 1999Sep 2015

First posted17 Mar 2010 (estimated)
Study startApr 1999
Primary completionSep 2015
Study completionSep 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Growth Hormone (GH) DeficiencyStudies of the same condition, open and under way.
More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 22,845 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01088412
Sponsor's protocol ID: 2712
Other IDs: B9R-EW-GDFC
Acronym: GeNeSIS
Status last verified: Jul 2018
First submitted: 25 Feb 2010
Last updated: 13 May 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Child CJ, Zimmermann AG, Chrousos GP, Cummings E, Deal CL, Hasegawa T, Jia N, Lawrence S, Linglart A, Loche S, Maghnie M, Perez Sanchez J, Polak M, Predieri B, Richter-Unruh A, Rosenfeld RG, Yeste D, Yorifuji T, Blum WF. Safety Outcomes During Pediatric GH Therapy: Final Results From the Prospective GeNeSIS Observational Program. J Clin Endocrinol Metab. 2019 Feb 1;104(2):379-389. doi: 10.1210/jc.2018-01189.
PubMed 30219920
Deal C, Kirsch S, Chanoine JP, Lawrence S, Cummings E, Rosolowsky ET, Marks SD, Jia N, Child CJ; GeNeSIS National Board on behalf of the GeNeSIS Canada Investigators. Growth hormone treatment of Canadian children: results from the GeNeSIS phase IV prospective observational study. CMAJ Open. 2018 Sep 10;6(3):E372-E383. doi: 10.9778/cmajo.20180020. Print 2018 Jul-Sep.
PubMed 30201821
Quigley CA, Child CJ, Zimmermann AG, Rosenfeld RG, Robison LL, Blum WF. Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders: Data From the Genetics and Neuroendocrinology of Short Stature International Study. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3195-3205. doi: 10.1210/jc.2017-00214.
PubMed 28575299
Blum WF, Deal C, Zimmermann AG, Shavrikova EP, Child CJ, Quigley CA, Drop SL, Cutler GB Jr, Rosenfeld RG. Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with idiopathic isolated GH deficiency. Eur J Endocrinol. 2013 Nov 22;170(1):13-21. doi: 10.1530/EJE-13-0643. Print 2014 Jan.
PubMed 24088548
Deal C, Hasselmann C, Pfaffle RW, Zimmermann AG, Quigley CA, Child CJ, Shavrikova EP, Cutler GB Jr, Blum WF. Associations between pituitary imaging abnormalities and clinical and biochemical phenotypes in children with congenital growth hormone deficiency: data from an international observational study. Horm Res Paediatr. 2013;79(5):283-92. doi: 10.1159/000350829. Epub 2013 May 16.
PubMed 23689058
Child CJ, Zimmermann AG, Scott RS, Cutler GB Jr, Battelino T, Blum WF; GeNeSIS International Advisory Board. Prevalence and incidence of diabetes mellitus in GH-treated children and adolescents: analysis from the GeNeSIS observational research program. J Clin Endocrinol Metab. 2011 Jun;96(6):E1025-34. doi: 10.1210/jc.2010-3023. Epub 2011 Apr 13.
PubMed 21490076

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 3
Phase 3 Study of LUM-201 in Children With Growth Hormone Deficiency
Growth Hormone Deficiency (GHD)
Not yet recruitingObservational study
The AgRP and GH/IGF-1 Axis in Children
Growth Hormone Deficiency
RecruitingPhase 4
Effects of GH and Lirglutide on AgRP
Healthy, Growth Hormone Deficiency

All Growth Hormone (GH) Deficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 13 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS)
ClinicalTrials.gov ID: NCT01088412
Acronym / sponsor ID: GeNeSIS / 2712
Conditions: Growth Hormone (GH) Deficiency, Short Stature Homeobox Containing Gene (SHOX) Deficiency, SHOX Deficiency-related Disorder, Non-GH-deficient Growth Disorders
Study type: Observational
Recruitment status: Completed
Enrolment: 22,845 participants (actual)
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Study start: Apr 1999
Primary completion: Sep 2015 (actual)
Study completion: Sep 2015 (actual)
First posted: 17 Mar 2010 (estimated)
Results: Posted 13 May 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

GeNeSIS is an open-label, multinational, multicenter, observational study to evaluate the safety and effectiveness of Humatrope treatment.

GeNeSIS is a modular program that includes:

Core study: Evaluating the safety and effectiveness of Humatrope in the observational setting
Genetic Analysis Sub-study: Investigating the genetic defects underlying growth hormone (GH) deficiency and non-GH-deficient growth disorders
Growth Prediction Sub-study: Working to validate and refine specific models to accurately predict growth response to GH
Short Stature Homeobox containing gene (SHOX) Deficiency Sub-study: Elucidating the clinical, endocrine and radiological features of participants with SHOX deficiency due to loss of, or mutation in the SHOX gene (including participants with Turner syndrome)
Neoplasia Sub-study: To characterize the natural history of neoplastic disease, especially in relation to recurrence/progression of primary neoplasia or development of secondary neoplasia in children with a history of neoplasia

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 2

Arm	Type	Receives
Treated	–	Drug: Somatropin (recombinant deoxyribonucleic acid [rDNA] origin)Participants treated with somatropin for improvement of growth
Untreated	–	–Untreated participants with presence or history of neoplastic disease evaluated for endocrine or growth disorder or with any SHOX deficiency related disorder

Who may qualify

Ages: 1 day and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult
Study population: Clinics and private practices

Key inclusion criteria (3 listed)

All participants participating in GeNeSIS must be enrolled in the core study. Participants for whom written consent to release information is provided may enter the core study if they meet any of the following inclusion guidelines:
Treatment with Humatrope for improvement of growth.
No treatment with somatropin in participants with a history of neoplasia or in those with any SHOX deficiency-related disorder.

Key exclusion criteria (1 listed)

Participants with closed epiphyses are not eligible for GeNeSIS entry. However, participants may remain in the study if epiphyseal closure occurs during study participation.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Somatropin (recombinant deoxyribonucleic acid [rDNA] origin)Also: Humatrope, LY137998Dose, frequency and duration at discretion of attending physician.	Drug	Treated

Primary outcome

Type 2 Diabetes Mellitus in GH-treated Participants
Time frame: Year 15
Primary Malignancies in Participant Without Previous Cancer History
Time frame: Year 15
Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated.
Final Height (FH) Gain by Diagnostic Group
Time frame: Baseline through Year 15
The standard deviation score (SDS) reports the number of standard deviations from the mean for age and sex for an individual measurement (normal range is -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated.

6 secondary outcomes

Percentage of Participants With Defects in Genes Associated With Pituitary Development
Time frame: Baseline through Year 15
Predicted First Year Height Gain Versus Actual First Year Height Gain
Time frame: Baseline through Year 15
Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency
Time frame: Baseline, Year 15
Percentage of Participants With Recurrent Neoplasms and Second Neoplasms in Childhood Cancer Survivors
Time frame: Baseline through Year 15
Percentage of Participants With De Novo Neoplasms
Time frame: Baseline through Year 15
Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses
Time frame: Baseline through Year 15

Results and safety

Results posted to the registry on 13 May 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treated	22,311	4,294
Untreated	457	21
FG002	77	5

Primary outcome: Type 2 Diabetes Mellitus in GH-treated Participants

Time frame: Year 15. Number. Unit: Incident Cases

Measure	Treated n = 21448
Ages 0 to 9	1
Ages 10 to 14	9
Ages 15 to 19	8

Treated: Standardized Incidence Ratio: 3.77 (95% CI 2.24 to 5.96)

Population analysed: All treated participants with available age and calculable follow-up time. The treated participants were not compared with untreated but with rates from general population registries. The untreated participants predominantly contained neoplasm or SHOX deficient diagnoses, therefore had significant baseline differences from treated participants.

Primary outcome: Primary Malignancies in Participant Without Previous Cancer History

Time frame: Year 15. Number. Unit: Incident Cases

Measure	Treated n = 20146
Value	14

Treated: Standardized Incidence Ratio: 0.71 (95% CI 0.39 to 1.20)

Population analysed: All treated participants with available age, gender, and at least one follow-up excluding participants with previous cancer cases. Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated.

Primary outcome: Final Height (FH) Gain by Diagnostic Group

Time frame: Baseline through Year 15. Mean (Standard Deviation). Unit: standard deviation score

Measure	Treated n = 5075
All Baseline Height	-2.42 (1.01)
All Final Height	-1.18 (1.12)
All Final Height Gain	1.24 (1.08)
GHD Baseline Height	-2.35 (1.04)
GHD Final Height	-0.96 (1.12)
GHD Final Height Gain	1.39 (1.14)
TS Baseline Height	-2.65 (.089)
TS Final Height	-1.70 (0.94)

Population analysed: All treated participants who reached final height (at least 1: closed epiphyses, height velocity \<2 centimeters per year, or last bone age \>14 years \[girls\] or \>16 years \[boys\]) with baseline height SDS and final height available. Data was not provided for untreated and unknown treatment groups, and could not be calculated.

6 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0.2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treated	547 of 21,177 (2.6%)	6,180 of 21,177 (29.2%)	Not reported
Untreated	14 of 306 (4.6%)	126 of 306 (41.2%)	Not reported
EG002	0 of 40 (0%)	0 of 40 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30219920Child CJ, Zimmermann AG, Chrousos GP, Cummings E, Deal CL, Hasegawa T, Jia N, Lawrence S, Linglart A, Loche S, Maghnie M, Perez Sanchez J, Polak M, Predieri B, Richter-Unruh A, Rosenfeld RG, Yeste D, Yorifuji T, Blum WF. Safety Outcomes During Pediatric GH Therapy: Final Results From the Prospective GeNeSIS Observational Program. J Clin Endocrinol Metab. 2019 Feb 1;104(2):379-389. doi: 10.1210/jc.2018-01189.
Derived from this study: PubMed 30201821Deal C, Kirsch S, Chanoine JP, Lawrence S, Cummings E, Rosolowsky ET, Marks SD, Jia N, Child CJ; GeNeSIS National Board on behalf of the GeNeSIS Canada Investigators. Growth hormone treatment of Canadian children: results from the GeNeSIS phase IV prospective observational study. CMAJ Open. 2018 Sep 10;6(3):E372-E383. doi: 10.9778/cmajo.20180020. Print 2018 Jul-Sep.
Derived from this study: PubMed 28575299Quigley CA, Child CJ, Zimmermann AG, Rosenfeld RG, Robison LL, Blum WF. Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders: Data From the Genetics and Neuroendocrinology of Short Stature International Study. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3195-3205. doi: 10.1210/jc.2017-00214.
Derived from this study: PubMed 24088548Blum WF, Deal C, Zimmermann AG, Shavrikova EP, Child CJ, Quigley CA, Drop SL, Cutler GB Jr, Rosenfeld RG. Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with idiopathic isolated GH deficiency. Eur J Endocrinol. 2013 Nov 22;170(1):13-21. doi: 10.1530/EJE-13-0643. Print 2014 Jan.
Derived from this study: PubMed 23689058Deal C, Hasselmann C, Pfaffle RW, Zimmermann AG, Quigley CA, Child CJ, Shavrikova EP, Cutler GB Jr, Blum WF. Associations between pituitary imaging abnormalities and clinical and biochemical phenotypes in children with congenital growth hormone deficiency: data from an international observational study. Horm Res Paediatr. 2013;79(5):283-92. doi: 10.1159/000350829. Epub 2013 May 16.
Derived from this study: PubMed 21490076Child CJ, Zimmermann AG, Scott RS, Cutler GB Jr, Battelino T, Blum WF; GeNeSIS International Advisory Board. Prevalence and incidence of diabetes mellitus in GH-treated children and adolescents: analysis from the GeNeSIS observational research program. J Clin Endocrinol Metab. 2011 Jun;96(6):E1025-34. doi: 10.1210/jc.2010-3023. Epub 2011 Apr 13.

Related trials for Growth Hormone (GH) Deficiency

RecruitingPhase 3
Phase 3 Study of LUM-201 in Children With Growth Hormone Deficiency
Growth Hormone Deficiency (GHD)
Not yet recruitingObservational study
The AgRP and GH/IGF-1 Axis in Children
Growth Hormone Deficiency
RecruitingPhase 4
Effects of GH and Lirglutide on AgRP
Healthy, Growth Hormone Deficiency

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) study director

Eli Lilly and Company

Questions about this trial

What is this clinical trial studying?

An observational study of Growth Hormone (GH) Deficiency and Short Stature Homeobox Containing Gene (SHOX) Deficiency, run by Eli Lilly and Company.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 May 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Type 2 Diabetes Mellitus in GH-treated Participants (time frame: Year 15). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01088412, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2019.

Trial summary

Key requirements

Who may be able to join

Who cannot join

About this study

What participants receive

What is being measured

Timeline

Resources

More details

Publications

Study at a glance

Clinical summary

Study design

Who may qualify

Key inclusion criteria (3 listed)

Key exclusion criteria (1 listed)

Interventions

Primary outcome

Results and safety

Participant flow

Primary outcome: Type 2 Diabetes Mellitus in GH-treated Participants

Primary outcome: Primary Malignancies in Participant Without Previous Cancer History

Primary outcome: Final Height (FH) Gain by Diagnostic Group

Adverse events

Research links

Related trials for Growth Hormone (GH) Deficiency

Phase 3 Study of LUM-201 in Children With Growth Hormone Deficiency

The AgRP and GH/IGF-1 Axis in Children

Effects of GH and Lirglutide on AgRP

Referral and contact

Questions about this trial

Participant flow

Primary outcome: Type 2 Diabetes Mellitus in GH-treated Participants

Primary outcome: Primary Malignancies in Participant Without Previous Cancer History

Primary outcome: Final Height (FH) Gain by Diagnostic Group

Adverse events