Study Testing Response Effect of KY1005 Against Moderate-to-Severe Atopic Dermatitis, The STREAM-AD Study

Sponsor

Kymab Limited (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05131477

Collaborator

Sanofi (Industry)

350

Enrollment

111

Locations

Arms

26.6

Anticipated Duration (Months)

3.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an interventional, randomized, parallel group, treatment, Phase IIb, double blind, 5-arm study to assess the effect of Anti-OX40L Monoclonal Antibody (KY1005) in adult participants with moderate to severe atopic dermatitis.

The estimated duration is 28 days for screening and then up to approximately day 477 (last dose no later than day 337+140 days safety follow-up) for all patients unless enrolled into the LTE protocol at either Day 169 depending on responder status or no later than Day 365 due to loss of clinical response.

Condition or Disease	Intervention/Treatment	Phase
Eczema Atopic Dermatitis	Drug: KY1005 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

350 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase IIb, Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Dose Ranging Study of a Subcutaneous Anti-OX40L Monoclonal Antibody (KY1005) in Moderate-to-Severe Atopic Dermatitis

Actual Study Start Date :

Mar 2, 2022

Anticipated Primary Completion Date :

Jun 12, 2023

Anticipated Study Completion Date :

May 20, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KY1005 Dose Level 1 Every 4 weeks	Drug: KY1005 Pharmaceutical form: Injection solution Route of administration: Subcutaneous Other Names: Amlitelimab SAR445229 A human anti-OX40 ligand monoclonal antibody
Experimental: KY1005 Dose Level 2 Every 4 weeks	Drug: KY1005 Pharmaceutical form: Injection solution Route of administration: Subcutaneous Other Names: Amlitelimab SAR445229 A human anti-OX40 ligand monoclonal antibody
Experimental: KY1005 Dose Level 3 Every 4 weeks	Drug: KY1005 Pharmaceutical form: Injection solution Route of administration: Subcutaneous Other Names: Amlitelimab SAR445229 A human anti-OX40 ligand monoclonal antibody
Experimental: KY1005 Dose Level 4 Every 4 weeks	Drug: KY1005 Pharmaceutical form: Injection solution Route of administration: Subcutaneous Other Names: Amlitelimab SAR445229 A human anti-OX40 ligand monoclonal antibody
Placebo Comparator: Placebo Every 4 weeks	Drug: Placebo Pharmaceutical form: Injection solution Route of administration: Subcutaneous

Outcome Measures

Primary Outcome Measures

Percentage change in EASI (Eczema Area and Severity Index) from Baseline [Baseline to Day 113]
The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.

Secondary Outcome Measures

Incidence of treatment-emergent adverse event [Baseline through Day 477]
Serum KY1005 concentration assessed throughout the study [Baseline through Day 477]
Percentage change in EASI (Eczema Area and Severity Index) from baseline to Day 169 [Baseline to Day 169]
The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.
Percentage of patients with at least a 75% reduction from Baseline in EASI (EASI 75) [At Days 113 and 169]
The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.
Percentage of patients with a response of IGA (Investigator Global Assessment) 0 or 1 and a reduction from baseline ≥ 2 points [At Days 113 and 169]
The IGA is a five-point scale that provides a global clinical assessment of AD severity ranging from 0 to 4, where 0 indicates clear, 2 is mild, 3 is moderate, and 4 indicates severe AD.
Proportion of patients with improvement (reduction) of weekly average of pruritus NRS (Numerical Rating Scale) ≥ 4 with a baseline pruritus of ≥ 4 from baseline [Days 113 and 169]
The pruritus NRS is a simple assessment tool to report the intensity of their pruritus (itch) ranges from 0 to 10 with 0 being 'no itch' and 10 being the 'worst itch imaginable'.
Absolute change from Baseline in EASI (Eczema Area and Severity Index) [At Days 15, 29, 57, 85, 113, 141 and 169]
The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.
Percentage change from Baseline in EASI (Eczema Area and Severity Index) [At Days 15, 29, 57, 85 and 141]
The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.
Percentage of patients with at least a 50% reduction from Baseline in EASI (EASI 50) [At Days 15, 29, 57, 85, 113, 141 and 169]
The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.
Percentage of patients with at least a 75% reduction from Baseline in EASI (EASI 75) [At Days 15, 29, 57, 85, and 141]
The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.
Percentage of patients with at least a 90% reduction from Baseline in EASI (EASI 90) [At Days 15, 29, 57, 85, 113, 141 and 169]
The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.
Percentage of patients with a 100% reduction from Baseline in EASI (EASI 100) [At Days 15, 29, 57, 85, 113, 141 and 169]
The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicate worse condition.
Change in IGA (Investigator Global Assessment) from Baseline [Baseline to day 113 and over time up to Day 365]
The IGA is a five-point scale that provides a global clinical assessment of AD severity ranging from 0 to 4, where 0 indicates clear, 2 is mild, 3 is moderate, and 4 indicates severe AD
Percentage of patients with a score of IGA (Investigator Global Assessment) 0 or 1 and a reduction from Baseline of ≥ 2 points [At Days 15, 29, 57, 85, and 141]
The IGA is a five-point scale that provides a global clinical assessment of AD (Atopic Dermatitis) severity ranging from 0 to 4, where 0 indicates clear, 2 is mild, 3 is moderate, and 4 indicates severe AD
Absolute and Percentage change in SCORAD (SCORing Atopic Dermatitis) Index from Baseline [Baseline to Day 169 and over time up to Day 365]
SCORAD was used to assess the extent and severity of AD (Atopic Dermatitis). Extent and severity of eczema as well as subjective assessment of symptoms were assessed and scored. SCORAD total score ranges from 0 (absent disease) to 103 (severe disease)
Absolute and Percentage change in affected BSA from Baseline [Baseline to Day 169 and over time up to Day 365]
Absolute and Percentage change in Patient Oriented Eczema Measure (POEM) from Baseline [Baseline to Day 169 and over time up to Day 365]
POEM is a 7-item (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) questionnaire to assess frequency of disease symptoms with a scoring system of 0 to 28. The higher score indicating higher severity
Absolute and Percentage change in Dermatology Life Quality Index (DLQI) from Baseline [Baseline to Day 169 and over time up to Day 365]
DLQI is a questionnaire with a score system of 0 to 30 the high score is indicative of poor QoL.
Absolute and Percentage change in Atopic Dermatitis Control Tool (ADCT) from Baseline [Baseline to Day 169 and over time up to Day 365]
ADCT is a questionnaire to assess patient-self-perceived control of their eczema with a total score from 0 to 24; higher scores indicate lower AD control
Absolute and Percentage change in Hospital Anxiety and Depression Scale (HADS) from Baseline [Baseline to Day 169 and over time up to Day 365]
HADS is a fourteen-item scale with seven items each for anxiety and depression subscales. Scoring for each item ranges from zero to three. A subscale score >8 denotes anxiety or depression
Absolute and Percentage change in weekly average of pruritus Numerical Rating Scale (NRS) from Baseline [Baseline to Day 169 and over time up to Day 365]
The pruritus NRS is a simple assessment tool to report the intensity of their pruritus (itch) ranges from 0 to 10 with 0 being 'no itch' and 10 being the 'worst itch imaginable'.
Proportion of patients with improvement (reduction) of weekly average of pruritus NRS (Numerical Rating Scale) ≥ 3 with a baseline pruritus NRS ≥ 3 from baseline [Baseline to Days 113 and 169]
The pruritus NRS is a simple assessment tool to report the intensity of their pruritus (itch) ranges from 0 to 10 with 0 being 'no itch' and 10 being the 'worst itch imaginable'.
Incidence of positive anti-Ky1005 antibody response [Baseline through Day 477]
Time to loss of EASI 75 [Week 24 to Day 365]
The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicates worse condition.
Time to loss of IGA 0/1 (Patients with a response of 0 or 1 in IGA) [Week 24 to Day 365]
The IGA is a five-point scale that provides a global clinical assessment of AD severity ranging from 0 to 4, where 0 indicates clear, 2 is mild, 3 is moderate, and 4 indicates severe AD.
Time to loss of EASI 50 [Week 24 to Day 365]
The EASI is a composite index with scores ranging from 0 to 72. Higher scores indicates worse condition.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults (18 to < 75 years of age) with AD as defined by the American Academy of Dermatology Consensus Criteria for 1 year or longer at Baseline.
EASI of 12 or higher at the Screening Visit and 16 or higher at Baseline.
IGA of 3 or 4 at Baseline.
AD involvement of 10% or more of body surface area (BSA) at Baseline.
Baseline worst/maximum pruritus NRS of ≥4.
Documented history, within 6 months prior to Baseline, of either inadequate response or inadvisability of topical treatments.
Must have applied a stable dose of topical bland emollient (simple moisturizer, no additives [e.g., urea]) at least twice daily for a minimum of 7 consecutive days before Baseline.
Able to complete patient questionnaires.
Able and willing to comply with requested study visits/telephone visits and procedures.
Able and willing to provide written informed consent.
For patients who decide to join the biopsy sub-study be able and willing to provide skin biopsies.

Exclusion Criteria:

Treatment within specific time windows before the baseline visit for the management of atopic dermatitis such as topical or systemic corticosteroids, biologic or investigational therapies and/or phototherapy.
Known history of, or suspected, significant current immunosuppression, including history of invasive opportunistic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
Weight <40 kg or >150 kg at Baseline.
Treatment with a live (attenuated) immunization within 12 weeks prior to Baseline.
Men and women (of reproductive potential) unwilling to use birth control and women who are pregnant or breastfeeding.
Any malignancies or history of malignancies prior to Baseline (except for non-melanoma skin cancer that has been excised and cured for more than 3 years prior to Baseline; in situ cervical carcinoma that has been excised and cured).
Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C at the screening visit.
Severe concomitant illness that would in the Investigator's opinion inhibit the patient's participation in the study, including for example, but not limited to, hypertension, renal disease, neurological conditions, heart failure and pulmonary disease.
In the Investigator's opinion, any clinically significant laboratory results from the clinical chemistry, hematology or urinalysis tests at the Screening Visit.
Concurrent participation in any other clinical study, including non-interventional studies.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigative Site Number: 1018	Fremont	California	United States	94538-1601
2	Investigative site #1022	Sacramento	California	United States	95816-3370
3	Investigative Site Number: 1006	Boca Raton	Florida	United States	33428
4	Investigative Site Number: 1001	Clearwater	Florida	United States	33756-3424
5	Investigative Site Number: 1019	Coral Gables	Florida	United States	33134-2950
6	Investigative Site Number: 1007	Miami	Florida	United States	33176-2264
7	Investigative Site Number: 1013	Tampa	Florida	United States	33615-3816
8	Investigative Site Number: 1004	Savannah	Georgia	United States	31406-2668
9	Investigative Site Number: 1010	Clarksville	Indiana	United States	47129-2201
10	Investigative Site Number: 1015	Indianapolis	Indiana	United States	46250-2041
11	Investigative Site Number: 1021	Louisville	Kentucky	United States	40241
12	Investigative Site Number: 1011	Towson	Maryland	United States	21204-7448
13	Investigative Site Number: 1014	Beverly	Massachusetts	United States	01915-1666
14	Investigative Site Number: 1012	Troy	Michigan	United States	48084-3536
15	Investigative Site Number: 1005	Tulsa	Oklahoma	United States	74136-7049
16	Investigative Site Number: 1017	Portland	Oregon	United States	97223-6683
17	Investigative Site Number: 1009	Portland	Oregon	United States	97239
18	Investigative Site Number: 1003	Anderson	South Carolina	United States	29621-2062
19	Investigative Site Number: 1008	Murfreesboro	Tennessee	United States	37130-2450
20	Investigative site #1023	Mansfield	Texas	United States	76063
21	Investigative Site Number: 1016	San Antonio	Texas	United States	78213-2250
22	Investigative Site Number 3002	Carlton		Australia	3053
23	Investigative Site Number: 3003	East Melbourne		Australia	3002
24	Investigational Site Number: 3001	Parkville		Australia	3050
25	Investigative Site Number: 2004	Pleven		Bulgaria	5800
26	Investigative Site Number: 2005	Sofia		Bulgaria	1431
27	Investigative Site Number: 2006	Sofia		Bulgaria	1592
28	Investigative Site Number: 2003	Sofia		Bulgaria	1612
29	Investigative Site Number: 2002	Sofia		Bulgaria	1784
30	Investigative Site Number: 2001	Stara Zagora		Bulgaria	6003
31	Investigative Site Number: 1106	Markham	Ontario	Canada	L3P 1X2
32	Investigative Site Number: 1103	Ottawa	Ontario	Canada	K2C 3N2
33	Investigative Site Number: 1107	Waterloo	Ontario	Canada	N2J 1C4
34	Investigative Site Number: 1101	Windsor	Ontario	Canada	N8W 1E6
35	Investigative site #1109	Montreal		Canada	H4G3E7
36	Investigative site #1108	Niagara Falls		Canada	L2H 1H5
37	Investigative Site Number: 2108	Brno	Jihomoravský Kraj	Czechia	602 00
38	Investigative Site Number: 2105	Nový Jicín	Moravskoslezský Kraj	Czechia	741 01
39	Investigative Site Number: 2107	Pardubice	Pardubický Kraj	Czechia	530 02
40	Investigative Site Number: 2101	Prague	Praha, Hlavní Mesto	Czechia	120 00
41	Investigative Site Number: 2102	Praha	Praha, Hlavní Mesto	Czechia	108 00
42	Investigative Site Number: 2103	Praha	Praha, Hlavní Mesto	Czechia	130 00
43	Investigative Site Number: 2106	Kutná Hora		Czechia	284 01
44	Investigative Site Number: 2104	Ostrava		Czechia	702 00
45	Investigative Site Number: 2209	Erlangen	Bayern	Germany	91054
46	Investigative Site Number: 2202	Blankenfelde	Brandenburg	Germany	15827
47	Investigator Site Number: 2201	Münster	Nordrhein-Westfalen	Germany	48149
48	Investigative Site Number: 2205	Dresden	Sachsen	Germany	1307
49	Investigative Site Number: 2206	Leipzig	Sachsen	Germany	4103
50	Investigative Site Number: 2208	Kiel	Schleswig-Holstein	Germany	2405
51	Investigative Site Number: 2207	Gera	Thüringen	Germany	7548
52	Investigative Site Number: 2203	Berlin		Germany	10117
53	Investigative Site Number: 2204	Hamburg		Germany	20251
54	Investigative Site Number: 2307	Kecskemét	Bács-Kiskun	Hungary	6000
55	Investigative Site Number: 2305	Gyula	Békés	Hungary	5700
56	Investigative Site Number: 2301	Szeged	Csongrád	Hungary	6720
57	Investigative Site Number: 2303	Debrecen	Hajdú-Bihar	Hungary	4032
58	Investigative Site Number: 2306	Szolnok	Jász-Nagykun-Szolnok	Hungary	5000
59	Investigative Site Number: 2302	Zalaegerszeg	Zala	Hungary	8900
60	Investigative Site Number: 2304	Budapest		Hungary	1036
61	Investigative Site Number: 3114	Obihiro-Shi	Hokkaidô	Japan	080-0013
62	Investigative site #3108	Kagoshima-Shi	Kagosima	Japan	890-0063
63	Investigative site #3113	Yokohama-Shi	Kanagawa	Japan	221-0825
64	Investigative Site Number: 3103	Matsudo	Tiba	Japan	270-2223
65	Investigative Site Number: 3112	Adachi-Ku	Tokyo	Japan	120-0034
66	Investigative Site Number: 3115	Chuo Ku	Tokyo	Japan
67	Investigative Site Number: 3104	Edagowa-Ku	Tokyo	Japan	133-0052
68	Investigative Site Number: 3111	Koto-Ku	Tokyo	Japan	136-0074
69	Investigative Site Number: 3107	Minato-Ku	Tokyo	Japan	108-0014
70	Investigative site #3105	Setagaya-Ku	Tokyo	Japan	158-0097
71	Investigative site #3102	Kyoto-Shi		Japan	602-0841
72	Investigative Site Number: 3106	Mibu-machi		Japan	321-0293
73	Investigative site #3101	Sapporo		Japan	060-0063
74	Investigative Site Number: 3109	Habikino-Shi	Ôsaka	Japan	583-0872
75	Investigative Site Number: 3110	Sakai-Shi	Ôsaka	Japan	593-8324
76	Investigative Site Number: 2414	Wrocław	Dolnoslaskie	Poland	50-088
77	Investigative Site Number: 2418	Wrocław	Dolnoslaskie	Poland	50-368
78	Investigative Site Number: 2417	Wrocław	Dolnoslaskie	Poland	51-685
79	Investigative Site Number: 2416	Łódź	Lodzkie	Poland	90-436
80	Investigative Site Number: 2415	Lódz	Lódzkie	Poland	90-127
81	Investigative site #2420	Łódź	Lódzkie	Poland	90-349
82	Investigative Site Number: 2420	Łódź	Lódzkie	Poland	90-349
83	Investigative Site Number: 2408	Kraków	Malopolskie	Poland	30-033
84	Investigative Site Number: 2407	Kraków	Malopolskie	Poland	30-510
85	Investigative Site Number: 2409	Kraków	Malopolskie	Poland	31-011
86	Investigative Site Number: 2412	Warszawa	Mazowieckie	Poland	00-874
87	Investigative Site Number: 2411	Warszawa	Mazowieckie	Poland	01-142
88	Investigative Site Number: 2413	Warszawa	Mazowieckie	Poland	01-192
89	Investigative Site Number: 2401	Rzeszów	Podkarpackie	Poland	35-055
90	Investigative site #2419	Bialystok	Podlaskie	Poland	15-879
91	Investigative Site Number: 2419	Białystok	Podlaskie	Poland
92	Investigative Site Number: 2402	Gdańsk	Pomorskie	Poland	80-382
93	Investigative Site Number: 2404	Gdynia	Pomorskie	Poland	81-384
94	Investigative Site Number: 2405	Katowice	Slaskie	Poland	40-040
95	Investigative Site Number: 2410	Szczecin	Zachodniopomorskie	Poland	71-434
96	Investigative site #2419	Białystok		Poland	15-879
97	Investigative Site Number: 2403	Gdańsk		Poland	80-592
98	Investigative Site Number: 2406	Krakow		Poland	31-559
99	Investigative site #2420	Łódź		Poland	90-349
100	Investigative Site Number: 2502	Manises	Valencia	Spain	46940
101	Investigative Site Number: 2505	Alicante		Spain	3010
102	Investigative Site Number: 2501	Córdoba		Spain	14004
103	Investigative Site Number: 2503	Madrid		Spain	28046
104	Investigative Site Number: 2504	Pontevedra		Spain	36001
105	Investigative Site Number: 3201	Niao Song Qu		Taiwan	833
106	Investigative Site Number: 3202	Taichung		Taiwan	402
107	Investigative site # 3206	Taipei		Taiwan	112217
108	Investigative Site Number: 3203	Taoyuan		Taiwan	33305
109	Investigative Site Number: 2603	London		United Kingdom	E11 1NR
110	Investigative Site Number: 2601	London		United Kingdom	SE1 9RT
111	Investigative Site Number: 2602	Sheffield		United Kingdom	S10 2TF