Study to Evaluate Imetelstat (GRN163L) in Subjects With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

Sponsor

Geron Corporation (Industry)

Overall Status

Recruiting

CT.gov ID

NCT02598661

Collaborator

(none)

278

Enrollment

136

Locations

Arms

94.6

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of imetelstat in transfusion dependent participants with low or intermediate-1 risk myelodysplastic syndrome (MDS) that is relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment in Part 1 of the study and to compare the efficacy, in terms of red blood cell (RBC) transfusion independence (TI), of imetelstat to placebo in transfusion dependent participants with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment in Part 2 of the study.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Drug: Imetelstat Drug: Placebo	Phase 2/Phase 3

Detailed Description

This is a Phase 2/3, multicenter study of imetelstat that consists of 2 parts and approximately 270 participants may be enrolled.

Part 1 is an open-label, single-arm design to assess the efficacy and safety of imetelstat. Approximately 55 participants were enrolled in Part 1, including the expansion cohort, and be followed-up for safety, hematologic improvement and reduction in transfusion requirement.

Part 2 is a double-blind, randomized design to compare the efficacy of imetelstat with placebo. In the main study in Part 2, 178 participants were enrolled and randomized in a 2:1 ratio to receive either imetelstat or placebo, respectively.

In a separate Ventricular Repolarization substudy of Part 2, approximately 45 participants will be enrolled and randomized 2:1 to receive either imetelstat or placebo. If after a minimum of 2 treatment cycles in the Ventricular Repolarization substudy, a participant has no significant change to pRBC transfusion burden or evidence of clinical benefit per Investigator, after discussion with the Sponsor the participant may be unblinded. If the participant was on placebo treatment, he/she may be permitted to start treatment with imetelstat.

Each part of the study will consist of 3 phases: a Screening phase (up to 28 days); a treatment phase; and a post-treatment follow-up phase which will continue until death, lost to follow-up, withdrawal of consent, or the End of the Study (whichever occurs first). The End of the Study is defined as 2 years after the study entry of the last participant in the main study of Part 2 or anytime the sponsor terminates the study, whichever comes first.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

278 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects With IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) That is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment

Actual Study Start Date :

Nov 24, 2015

Anticipated Primary Completion Date :

Jan 15, 2023

Anticipated Study Completion Date :

Oct 13, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Imetelstat Imetelstat will be administered at a starting dose of 7.5 milligram per kilogram (mg/kg) given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.	Drug: Imetelstat Intravenous injection. Other Names: GRN163L
Experimental: Part 2 (Main Study): Imetelstat Imetelstat will be administered at a starting dose of 7.5 mg/kg given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.	Drug: Imetelstat Intravenous injection. Other Names: GRN163L
Placebo Comparator: Part 2 (Main Study): Placebo Matching Placebo to Imetelstat will be administered.	Drug: Placebo Matching Placebo to Imetelstat will be administered.
Experimental: Part 2 (Ventricular Repolarization Substudy): Imetelstat Imetelstat will be administered at a starting dose of 7.5 mg/kg given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.	Drug: Imetelstat Intravenous injection. Other Names: GRN163L
Placebo Comparator: Part 2 (Ventricular Repolarization Substudy): Placebo Matching Placebo to Imetelstat will be administered.	Drug: Placebo Matching Placebo to Imetelstat will be administered.

Outcome Measures

Primary Outcome Measures

Part 1 and Part 2 (Main Study): Percentage of Participants Without any Red Blood Cell (RBC) Transfusion During any Consecutive 8-Week Period [Approximately 12 months]

Secondary Outcome Measures

Number of Participants with Adverse Events (AEs) [During study (approximately 2 years)]
Percentage of Participants Without any RBC Transfusion During any Consecutive 24-Week Period [During study (approximately 2 years)]
Time to the 8-Week RBC Transfusion Independence (TI) [During study (approximately 2 years)]
Duration of RBC TI [During study (approximately 2 years)]
Percentage of Participants with Hematologic Improvement [During study (approximately 2 years)]
Percentage of Participants with Complete Remission (CR) or Partial Remission (PR) as Per International Working Group (IWG) Response Criteria 2006 [During study (approximately 2 years)]
Overall Survival [During study (approximately 2 years)]
Progression Free Survival (PFS) [During study (approximately 2 years)]
Progression free survival will be assessed as the time interval from study Day 1 to the first date of disease progression or death from any cause, whichever occurs first. As per IWG criteria disease progression is defined as: at least one of the following: at least 50 percent (%) decrement from maximum response levels in granulocytes or platelets; reduction in hemoglobin by greater than or equal to (>=) 1.5 gram per deciliter (g/dL); transfusion dependence.
Time to Progression to Acute Myeloid Leukemia [During study (approximately 2 years)]
Amount of RBC Transfusions [During study (approximately 2 years)]
Relative Change in RBC Transfusions [During study (approximately 2 years)]
Percentage of Participants Receiving any Myeloid Growth Factors [During study (approximately 2 years)]
Maximum Observed Plasma Concentration (Cmax) [During study (approximately 2 years)]
Area Under the Drug Concentration-Plasma Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) [During study (approximately 2 years)]
Percentage of Participants with Antibodies to Imetelstat [During study (approximately 2 years)]
Part 2 (Main Study): Medical Resource Utilization Data [During study (approximately 2 years)]
Part 2 (Main Study): Assessment of Functional Assessment of Cancer Therapy-Anemia-Related Effects (FACT-An) [During study (approximately 2 years)]
The Functional Assessment of Cancer Therapy Anemia (FACT-An), is included in order to provide an assessment of the subject's functional status, well-being, and symptoms over time.
Part 2 (Main Study): Assessment of EuroQol 5 Dimension Questionnaire (EQ-5D-5L) [During study (approximately 2 years)]
The EQ-5D-5L is a generic measure of health status. EQ-5D-5L is a 5 item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Part 2 (Main Study): Assessment of Quality of Life in Myelodysplasia Scale (QUALMS) [During study (approximately 2 years)]
The QUALMS is a 38-item measure that assesses health-related quality of life for patients with MDS. Thirty-three items are used to calculate the total score, as well as the 14 item physical burden (QUALMS-P), 3-item benefit-finding (QUALMS-BF), and 11-item emotional burden (QUALMS-E) subscales.
Part 2 (Main Study): Assessment of Participant Global Impression of Change (PGIC) [During study (approximately 2 years)]
The Participant Global Impression of Change (PGIC) is a single-item questionnaire designed to provide an overall assessment of treatment from the participant's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of "very much improved" or "much improved".
Part 2 (Ventricular Repolarization Substudy): Change in QT Interval by Fridericia's Correction Method [Baseline and Day 1]
Change from baseline in QTc interval by Fridericia's correction method (ΔQTcF) will be assessed in participants in the Ventricular Repolarization substudy.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Man or woman greater than or equal to (>=) 18 years of age
Diagnosis of myelodysplastic syndrome (MDS) according to World Health Organization (WHO) criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to Cycle 1 Day 1 (C1D1) (Part 1) or randomization [Part 2 (Main Study)]. In Part 2 (Ventricular Repolarization Substudy), diagnosis of MDS or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) according to WHO criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to C1D1
International Prognostic Scoring System (IPSS) low Risk or intermediate-1 risk MDS
Red blood cell (RBC) transfusion dependent, defined as requiring at least 4 RBC units transfused over an 8-week period during the 16 weeks prior to Study Entry; pre-transfusion hemoglobin (Hb) should be less than or equal to 9.0 gram per deciliter (g/dL) to count towards the 4 units total
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

Participant has known allergies, hypersensitivity, or intolerance to imetelstat or its excipients
Participant has received an investigational drug or used an invasive investigational medical device within 30 days prior to Study Entry or is currently enrolled in an investigational study
Prior treatment with imetelstat
Have received corticosteroids greater than (>) 30 milligram per day (mg/day) prednisone or equivalent, or growth factor treatment within 4 weeks prior to study entry
Has received an erythropoiesis-stimulating agent (ESA) or any chemotherapy, immunomodulatory, or immunosuppressive therapy within 4 weeks prior to study entry (8 weeks for long-acting ESAs)
Part 2 (Main Study): a) Prior treatment with a hypomethylating agent (example [eg], azacitidine, decitabine); b) Prior treatment with lenalidomide

Additional Exclusion Criteria for Part 2 (Ventricular Repolarization Substudy)

Concurrent therapy with medications known to prolong the QT interval and have been associated with Torsade de pointes arrythmia (TdP)
Cardiac function abnormalities on screening ECG as follows:
Resting heart rate outside of 50 to 100 beats per minute
QTcF >470 millisecond (msec) determined by central assessment based on the average value of a triplicate set of ECGs
Diagnosed or suspected congenital long QT syndrome
Family history of sudden unexpected death from cardiac-related causes if indicative of a pathogenic mutation of cardiac ion channels
Family history of congenital long QT syndrome
History of Mobitz II second degree or third degree heart block
Implantable pacemaker or automatic implantable cardioverter defibrillator
Complete bundle branch block or ventricular conduction delay (QRS >119 msec)
Chronic or persistent atrial arrhythmia including atrial fibrillation and atrial flutter
History or presence of clinically relevant heart rhythm disturbances including atrial, junctional, re-entry, and ventricular tachycardia
Unusual T-wave morphology (i.e., bifid T-wave) likely to interfere with QT measurements
History or evidence for any of the following: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (example, pulmonary embolism, cerebrovascular accident including transient ischemic attacks) within 12 months prior to Cycle 1 Day 1, New York Heart Association (NYHA) Class II to IV heart disease
Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] ≥160 mmHg or diastolic BP ≥100 mmHg). Participants with a history of hypertension are permitted, provided that BP is controlled to within these limits by anti-hypertensive treatment
Any skin condition likely to interfere with electrocardiographic electrode placement or adhesion
History of thoracic surgery likely to cause abnormality of the electrical conduction through thoracic tissues

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Comprehensive Cancer Center	Birmingham	Alabama	United States	35294
2	Acrc/Arizona Clinical Research, Inc.	Tucson	Arizona	United States	85715
3	CBCC Global Research, Inc.	Bakersfield	California	United States	93309
4	UCLA Ronald Regan Medical Center	Los Angeles	California	United States	90095
5	Yale-New Haven Hospital (YNHH) - Smilow Cancer Hospital	New Haven	Connecticut	United States	06510-3220
6	BRCR Medical Center	Plantation	Florida	United States	33326
7	University of South Florida (USF) - H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
8	University of Chicago	Chicago	Illinois	United States	60637-1426
9	Franciscan Health	Indianapolis	Indiana	United States	46237-8601
10	St. Agnes Healthcare, Inc	Baltimore	Maryland	United States	21229-5201
11	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
12	Mayo Clinic Rochester	Rochester	Minnesota	United States	55902
13	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
14	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131
15	Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects	New York	New York	United States	10029
16	Columbia Presbyterian	New York	New York	United States	10032
17	Columbia University Medical Center	New York	New York	United States	10032
18	Weill Cornell Medical College-New York Presbyterian Hospital	New York	New York	United States	10065
19	Cleveland Clinic Taussig Cancer	Cleveland	Ohio	United States	44195
20	The Ohio State Comprehensive Cancer Center	Columbus	Ohio	United States	43210
21	Prairie lakes Healthcare system, Inc	Watertown	South Dakota	United States	57201
22	Tennessee Oncology at Centennial Medical Center	Nashville	Tennessee	United States	37203
23	Vanderbilt University Medical - Hematology-Oncology	Nashville	Tennessee	United States	37232-6307
24	Texas Oncology/Methodist Charlton Cancer Center	Dallas	Texas	United States	75237
25	Simmons Comprehensive Cancer Center	Dallas	Texas	United States	75390
26	Fred Hutchinson Cancer Research Center (FHCRC)	Seattle	Washington	United States	98109-1024
27	GZA Ziekenhuizen - Campus Sint	Wilrijk	Antwerpen	Belgium	2610
28	UZ Gent	Ghent	Oost-Vlaanderen	Belgium	9000
29	AZ Sint-Jan Burgge-Oostende	Brugge	West-Vlaanderen	Belgium	8000
30	Az Groeninge	Kortrijk	West-Vlaanderen	Belgium	8500
31	ZNA Middelheim	Antwerpen		Belgium	2020
32	ZNA Stuyvenberg Antwerpen	Antwerpen		Belgium	2610
33	AZ Klina	Brasschaat		Belgium	2930
34	Algemeen Ziekenhuis Sint-Jan	Brugge		Belgium	8000
35	Universitair Ziekenhuis Gent	Gent		Belgium	9000
36	UZ Leuven - Campus Gasthuisberg	Leuven		Belgium	3000
37	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
38	University of Alberta Hospital - Hematology Research	Edmonton	Alberta	Canada	T6G 2R3
39	The Ottawa Hospital	Ottawa	Ontario	Canada	K1G 8L6
40	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
41	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2L7
42	Jewish General Hospital	Montréal	Quebec	Canada	H3T 1E2
43	Fakultni nemocnice Brno	Brno	Brno-město	Czechia	625 00
44	FN Hradec Kralove	Hradec Králové		Czechia	50005
45	FN Kralovske Vinohrady	Praha 10		Czechia	100 34
46	Vseobecna fakultni nemocnice v Praze	Praha 2		Czechia	128 08
47	Hopital de l'Archet	Nice	Alpes-Maritimes	France	6202
48	CHU Tours	Tours	Centre	France	37044
49	CHU de Limoges, Hopital Dupuytren	Limoges	Haute-Vienne	France	87042
50	CHU de Grenoble - Hôpital Albe	La Tronche	Isère	France	38700
51	CHRU Nancy Brabois	Vandœuvre-lès-Nancy	Meurthe-et-Moselle	France	54511
52	CH Le Mans - HAEMATOLOGY	Le Mans	Sarthe	France	72037
53	Hopital Paul Brousse - Aphp Hôpitaux Universitaires Paris Su	Villejuif	Val-de-Marne	France	94804
54	CHU de Poitiers	Poitiers	Vienne	France	86021
55	Centre Hospitalier Universitai	Angers		France	49100
56	CHRU de Lille - Hopital Claude Huriez - Maladies du Sang	Lille		France	59037
57	CHU - HÃ´pital Saint Louis - H	Paris	Île-de-France	France	75010
58	University Hospital Freiburg	Freiburg	Baden-Württemberg	Germany	79106
59	Fachärztliche Gemeinschaftspraxis mit Schwerpunkt	Dresden	Sachsen	Germany	1307
60	University Hospital Leipzig	Leipzig	Sachsen	Germany	4107
61	Studienzentrum für Hämatologie, Onkologie,Diabetologie, Endoskopie und Fußambulanz	Aschaffenburg		Germany	63739
62	University Hospital Bonn	Bonn		Germany	53127
63	Universitatsklinikum Carl Gustav Carcus Dresden	Dresden		Germany	01307
64	Universitätsklinikum Düsseldorf	Duesseldorf		Germany	40225
65	Johannes Gutenberg Universität	Mainz		Germany	55131
66	Kaplan Medical Center	Reẖovot	Hagalil Saint	Israel	7610001
67	The Edith Wolfson Medical Center	H̱olon	HaMerkaz	Israel	58100
68	Meir Medical Center	Kfar Saba	HaMerkaz	Israel	44281
69	Ha'Emek Medical Center	Afula	HaZafon	Israel	1834111
70	Tel Aviv Sourasky Medical Center	Tel Aviv	Tel-Aviv	Israel	49372
71	The Chaim Sheba Medical Center	Tel HaShomer	Tel-Aviv	Israel	5265601
72	Carmel MC	Haifa		Israel	3436212
73	Hadassah Medical Organization	Jerusalem		Israel	9112001
74	Rabin Medical Center, Beilinson Hospital	Petah Tikva		Israel	4941492
75	A.O. Ospedale Niguarda Ca' Granda	Milano	Lombardia	Italy	20162
76	Istituto Clinico Humanitas Rozzano, IRCCS	Rozzano	Milano	Italy	20089
77	Irccs Crob	Rionero In Vulture	Potenza	Italy	85028
78	AOU Ospedali Riuniti Umberto I G.M. Lancisi G. Salesi	Ancona		Italy	60020
79	Policlinico Sant'Orsola Malpighi	Bologna		Italy	40138
80	Azienda Ospedaliera Universitaria Careggi di Firenze	Firenze		Italy	50134
81	IRCCS Policlinico San Matteo	Pavia		Italy	27100
82	A.O. Ospedali Riuniti Marche Nord Presidio Ospedaliero S. Salvatore di Pesaro-Stabilim. di Muraglia	Pesaro		Italy	61122
83	Grande Ospedale Metropolitano 'Bianchi-Melacrino-Morelli' Reggio Calabria	Reggio Calabria		Italy	89124
84	A.O. Universitaria Policlinico Tor Vergata	Roma		Italy	00133
85	AO S. Andrea, Università degli Studi di Roma La Sapienza	Roma		Italy	189
86	Ospedale di Circolo, PO Varese	Varese		Italy	21100
87	Gachon University Gil Medical Center - oncology	Incheon	Incheon Gwang'yeogsi	Korea, Republic of	21565
88	Pusan National University Hospital - Hematology and Oncology	Seogu	Incheon	Korea, Republic of	42941
89	Seoul National University Hospital	Seoul	Seoul Teugbyeolsi	Korea, Republic of	03080
90	Chonnam National University Hwasun Hospital	Hwasun	South Jeolla	Korea, Republic of	58128
91	Asan Medical Center	Seoul		Korea, Republic of	05505
92	Samsung Medical Center	Seoul		Korea, Republic of	06351
93	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
94	Severance Hospital, Yonsei Uni	Seoul		Korea, Republic of	3722
95	Radboud Umcn	Nijmegen	Gelderland	Netherlands	6525 GA
96	Meander Medisch Centrum	Amersfoort		Netherlands	3813 TZ
97	VU Medisch Centrum	Amsterdam		Netherlands	1081 HV
98	Universitair Medisch Centrum Groningen	Groningen		Netherlands	9713 GZ
99	Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego	Wrocław	Dolnoslaskie	Poland	50-367
100	Centrum Medyczne Pratia Poznan	Skorzewo	Kościerzyna	Poland	60-185
101	Wojewódzki Szpital Specjalistyczny sp.z o.o.	Słupsk	Pomorskie	Poland	76-200
102	SPZOZ MSWiA z Warminsko - Mazurskim Centrum Onkologii	Olsztyn	Warminsko-mazurskie	Poland	10-228
103	Ars Medical sp. z o.o.	Piła	Wielkopolskie Województwo	Poland	64-920
104	Clinics of Samarskiy GMU	Samara	Volga	Russian Federation	443079
105	Emergency Hospital of Dzerzhinsk	Dzerzhinsk		Russian Federation	606019
106	City Clinical Hospital	Moscow		Russian Federation	129301
107	Nizhniy Novgorod Region Clinical Hospital	Nizhny Novgorod		Russian Federation	603126
108	Ryazan Regional Clinical Hospital	Ryazan		Russian Federation	390039
109	FGU-Russian Research Institut	Saint Petersburg		Russian Federation	191024
110	Oncologic Dispensary No.2	Sochi		Russian Federation	354057
111	H.U.Pta.del Mar	Cadiz	Cádiz	Spain	11009
112	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid	Spain	28222
113	Hospital de Cruces	Baracaldo	Vizcaya	Spain	48903
114	Hosp. Univ. Germans Trias I Pujol	Badalona		Spain	08916
115	Hosp. Univ. Vall D Hebron	Barcelona		Spain	08035
116	Hosp. Clinic I Provincial de Barcelona	Barcelona		Spain	08036
117	Hosp. Gral. Univ. Gregorio Maranon	Madrid		Spain	28007
118	Hosp. Univ. La Paz	Madrid		Spain	28046
119	Hosp. Clinico Univ. de Salamanca	Salamanca		Spain	37007
120	Hospital Universitario Nuestra Señora de Valme	Sevilla		Spain	41014
121	Hospital Universitario Doctor	Valencia		Spain	46017
122	Hospital Universitari i Politecnic La Fe	Valencia		Spain	46026
123	University Hospital in Basel	Basel	Basel-Stadt (de)	Switzerland	4031
124	Kantonsspital St. Gallen - Onkologie/Hämatologie	Saint Gallen	Sankt Gallen	Switzerland	9007
125	Inselspital - Universitätsspital Bern	Bern		Switzerland	3010
126	Universitaetsspital Zuerich	Zuerich		Switzerland	8091
127	Ankara University Medical Faculty - Hematology	Ankara	Anatolia	Turkey	6590
128	Cukurova University Medical Faculty	Adana		Turkey	1330
129	Ege Universitesi Tip Fakultesi - Hematology	İzmir		Turkey	35040
130	KZ "Miska bahatoprofilna klinichna likarnia No4", hematolohi	Dnipropetrovs'k	Dnipropetrovs'ka Oblast'	Ukraine	49102
131	Instytut patolohii krovi ta transfusiynoi medytsyny NAMN Ukr	Lviv	L'vivs'ka Oblast'	Ukraine	79044
132	KNP "Cherkaskyi oblasnyi onkolohichnyi dyspanser Cherkaskoi	Cherkasy		Ukraine	18009
133	Nottingham City Hospital - Clinical Haematology	Nottingham	Nottinghamshire	United Kingdom	NG5 1PB
134	Aberdeen Royal Infirmary	Aberdeen		United Kingdom	AB252ZL
135	The Leeds Teaching Hospitals NHS Trust	Leeds		United Kingdom	LS9 7TF
136	Southampton University Hospital	Southampton		United Kingdom	SO16 6YD