臨床研究等提出・公開システム

A Randomized, Active-comparator, Observer-blind, Phase I/II/III Study to Demonstrate the Immunogenicity of a Single Booster Dose of DS-5670a in Adults and Elderly Received a Primary Series of Approved COVID-19 Vaccine

A Randomized, Active-comparator, Observer-blind, Phase I/II/III Study to Demonstrate the Immunogenicity of a Single Booster Dose of DS-5670a in Adults and Elderly Received a Primary Series of Approved COVID-19 Vaccine

5003

1) Dose escalation part: i) Subjects who have completed the initial series of Comirnaty 24 subjects (12 adults and 12 elderly) were randomised and administered the investigational product. The average age (standard deviation [SD]) of participants in the placebo, DS-5670a 10ug, 30ug, and 60ug group were as follows: For adults, 48.3 (10.50), 43.0 (16.09), 36.3 (15.01), and 49.7 (14.74) years, while for elderly, 69.0 (3.61), 70.7 (4.93), 70.0 (4.36), and 67.7 (2.08) years, respectively. Among adults, in the placebo and DS-5670a 60ug group, there were 2 males (66.7%) and 1 female (33.3%) each, while in DS-5670a 10ug and 30ug groups, there were 1 male (33.3%) and 2 females (66.7%) each. Among elderly, in the placebo, DS-5670a 10ug, and 60ug group, there were 3 males (100.0%) and 0 females each, while in DS-5670a 30ug group, there were 2 males (66.7%) and 1 female (33.3%). ii) Subjects who have completed the initial series of Spikevax 24 subjects (12 adults and 12 elderly) were randomised and administered the investigational product. The average age (standard deviation [SD]) of participants in the placebo, DS-5670a 10ug, 30ug, and 60ug group were as follows: For adults, 47.7 (17.10), 45.3 (12.06), 52.7 (13.65), and 55.3 (3.79) years, while for elderly, 70.3 (2.31), 67.7 (0.58), 71.0 (2.00), and 68.3 (2.52) years, respectively. Among adults, in the placebo, DS-5670a 10ug, and 60ug group, there were 3 males (100.0%) and 0 females each, while in DS-5670a 30ug group, there were 2 males (66.7%) and 1 female (33.3%). Among elderly, in the placebo and DS-5670a 30ug group, there were 2 males (66.7%) and 1 female (33.3%) each, while in DS-5670a 10ug and 60ug group, there were 1 male (33.3%) and 2 females (66.7%) each. There were no significant differences in baseline characteristics based on demographics and other criteria between adults and the elderly, regardless of the type of initial vaccine series. 2) Parallel comparison part: i) Subjects who have completed the initial series of Comirnaty 240 subjects (120 adults and 120 elderly) were randomised and administered the investigational product. The average age (standard deviation [SD]) of participants in the Comirnaty, DS-5670a 10ug, 30ug, and 60ug group were as follows: For adults, 51.7 (10.18), 50.2 (8.99), 49.4 (12.26), and 43.5 (12.23) years, while for elderly, 68.3 (3.53), 68.5 (3.35), 69.4 (3.05), and 68.5 (2.99) years, respectively. Among adults, in the Comirnaty group, there were 12 males (40.0%) and 18 females (60.0%), in DS-5670a 10ug and 30ug group, there were 8 males (26.7%) and 22 females (73.3%) each, and in DS-5670a 60ug group, there were 14 males (46.7%) and 16 females (53.3%). Among elderly, in the Comirnaty and DS-5670a 30ug group, there were 14 males (46.7%) and 16 females (53.3%) each, in DS-5670a 10ug group, there were 16 males (53.3%) and 14 females (46.7%), and in DS-5670a 60ug group, there were 15 males (50.0%) and 15 females (50.0%). ii) Subjects who have completed the initial series of Spikevax 197 subjects (120 adults and 77 elderly) were randomised and administered the investigational product. The average age (standard deviation [SD]) of participants in the Spikevax, DS-5670a 10ug, 30ug, and 60ug group were as follows: For adults, 50.3 (9.24), 50.5 (8.46), 45.4 (9.95), and 48.8 (8.94) years, while for elderly, 68.4 (2.57), 67.7 (2.42), 68.2 (3.22), and 68.2 (2.60) years, respectively. Among adults, in the Spikevax group, there were 16 males (51.6%) and 15 females (48.4%), in DS-5670a 10ug group, there were 20 males (66.7%) and 10 females (33.3%), in DS-5670a 30ug group, there were 14 males (48.3%) and 15 females (51.7%), and in DS-5670a 60ug group, there were 14 males (46.7%) and 16 females (53.3%). Among elderly, in the Spikevax group, there were 14 males (73.7%) and 5 females (26.3%), in DS-5670a 10ug group, there were 12 males (63.2%) and 7 females (36.8%), in DS-5670a 30ug group, there were 18 males (94.7%) and 1 female (5.3%), and in DS-5670a 60ug group, there were 17 males (85.0%) and 3 females (15.0%). Comparing adults and the elderly, apart from differences in age distribution and average age between the treatment groups, as well as a higher proportion of males among the elderly who completed the initial series of Spikevax, there were no significant differences in baseline characteristics based on demographics and other criteria between adults and the elderly, regardless of the type of initial vaccine series. 3) Non-inferiority verification part i) Subjects who have completed the initial series of Comirnaty 2311 subjects (1540 in the DS-5670a group and 771 in the Comirnaty group) were randomized and 2307 were administered the investigational product excluding 2 subjects each from the DS-5670a group and the Comirnaty group. The average age (standard deviation [SD]) of participants in the Comirnaty and the DS-5670a group were 44.9 (12.50) and 45.1 (12.89) years, respectively. In the Comirnaty group, there were 391 males (50.8%) and 378 females (49.2%), while in the DS-5670a group, there were 749 males (48.7%) and 789 females (51.3%). ii) Subjects who have completed the initial series of Spikevax 2207 subjects (1473 in the DS-5670a group and 734 in the Spikevax group) were randomized and 2204 were administered the investigational product excluding 3 subjects from the DS-5670a group. The average age (standard deviation [SD]) of participants in the Spikevax and the DS-5670a group were 40.9(12.75) and 41.2(12.84) years, respectively. In the Spikevax group, there were 436males (59.3%) and 299 females (40.7%), while in the DS-5670a group, there were 848 males (57.7%) and 621 females (42.3%). Regardless of the type of initial series, there were no significant differences in baseline characteristics based on demographics and other criteria between adults and the elderly, regardless of the type of initial vaccine series.

1) Dose escalation part: i) Subjects who have completed the initial series of Comirnaty 24 subjects (12 adults and 12 elderly) were randomised and all were included in the Full Analysis Set (FAS). One from the placebo group in adults was excluded from the Per Protocol Set (PPS), while all elderly were included in the PPS. ii) Subjects who have completed the initial series of Spikevax 24 subjects (12 adults and 12 elderly) were randomised and all were included in the FAS. One from the placebo group in adults was excluded from the PPS, while all elderly were included in the PPS. 2) Parallel comparison part: i) Subjects who have completed the initial series of Comirnaty 240 subjects (120 adults and 120 elderly) were randomised and all were included in both the FAS and PPS. ii) Subjects who have completed the initial series of Spikevax 197 subjects (120 adults and 77 elderly) were randomised and all were included in the FAS. One adult randomised to the DS-5670a 30ug group administered the Spikevax prepared for another subject by mistake. This subject was included in the DS-5670a 30ug group in the FAS but excluded from the PPS. 3) Non-inferiority verification part: i) Subjects who have completed the initial series of Comirnaty 2311 subjects (1540 in the DS-5670a group and 771 in the Comirnaty group) were randomized. 2307 subjects excluding 2 subjects each from the DS-5670a group and the Comirnaty group who did not be administered the investigational product were included in the Efficacy Evaluable FAS. Among them, 7 from the DS-5670a group and 3 from the Comirnaty group were excluded from the Efficacy Evaluable PPS due to serious protocol deviations. Out of the randomised 2311 subjects, 211 (142 in the DS-5670a group and 69 in the Comirnaty group) were included in the Immunogenicity Evaluable FAS. Among them, 2 from the DS-5670a group were excluded from the Immunogenicity Evaluable PPS due to serious protocol deviations. ii) Subjects who have completed the initial series of Spikevax 2207 subjects (1473 in the DS-5670a group and 734 in the Spikevax group) were randomized. 2204 subjects excluding 3 subjects from the DS-5670a group who did not be administered the investigational product were included in the Efficacy Evaluable FAS. Among them, 2 subjects from the DS-5670a group and 3 subjects from the Spikevax group were excluded from the Efficacy Evaluable PPS due to serious protocol deviations. Out of the randomised 2207 subjects, 212 (142 in the DS-5670a group and 70 in the Spikevax group) were included in both the Immunogenicity Evaluable FAS and Immunogenicity Evaluable PPS.

Non-inferiority verification part: i) Subjects who have completed the initial series of Comirnaty The incidence of adverse events was 95% or higher in both the DS-5670a group and the Comirnaty group. The incidence of severe adverse events was 7.1% (109/1538) in the DS-5670a group and 5.9% (45/769) in the Comirnaty group. Except for 1 subject in the DS-5670a group and 2 subjects in the Comirnaty group, all severe adverse events were considered to be related to the investigational product. There were no deaths or adverse events leading to discontinuation of the investigational product. The incidence of solicited injection site adverse events was not different significantly between the DS-5670a group and the Comirnaty group. There were no significant differences in the incidence of individual solicited injection site adverse events between the two treatment groups. The most commonly observed solicited injection site adverse events in both groups were injection site pain and injection site warmth. The results were consistent for all side effects. The incidence of severe solicited injection site adverse events was 2.8% (43/1538) in the DS-5670a group and 1.8% (14/769) in the Comirnaty group. The most commonly observed events in the DS-5670a group were injection site warmth and injection site erythema (15 participants each), while in the Comirnaty group, injection site warmth (7 participants) was the most common. The incidence of solicited systemic adverse events was not different significantly between the DS-5670a group and the Comirnaty group. There were no significant differences in the incidence of individual solicited systemic adverse events between the two treatment groups. The most commonly observed solicited systemic adverse events in both groups were malaise, headache, and fever. The results were consistent for all side effects. The incidence of severe solicited systemic adverse events was 4.4% (68/1538) in the DS-5670a group and 4.3% (33/769) in the Comirnaty group. The most commonly observed event in the DS-5670a group was fever (42 subjects), while in the Comirnaty group, fever and malaise (17 subjects each). The incidence of unsolicited adverse events was not different significantly between the DS-5670a group and the Comirnaty group. The most commonly observed unsolicited adverse events in the DS-5670a group were injection site erythema, injection site swelling, injection site induration, and fever. The results were consistent for all side effects. The incidence of severe specific non-local adverse events was 0.7% (10/1538) in the DS-5670a group and 0.4% (3/769) in the Comirnaty intramuscular injection group. The most commonly observed event in the DS-5670a group was injection site erythema (5 subjects), while in the Comirnaty intramuscular injection group, axillary pain, chills, and meniscus injury (1 subject each) were observed. Among them, injection site erythema in the DS-5670a group and axillary pain and chills in the Comirnaty group were considered to be related to the investigational product. One subject in the DS-5670a group died (event: death). Based on the temporal relationship, this event was determined to be "not related" with the investigational product. ii) Subjects who have completed the initial series of Comirnaty The incidence of adverse events was 95% or higher in both the DS-5670a group and the Spikevax group. The incidence of severe adverse events was 10.1% (149/1469) in the DS-5670a group and 10.9% (80/735) in the Spikevax group. Except for 5 in the DS-5670a group and 1 in the Spikevax group, all severe adverse events were considered to be related to the investigational product. There were no deaths or adverse events leading to discontinuation of the investigational product. The incidence of solicited injection site adverse events was not different significantly between the DS-5670a group and the Spikevax group. There were no significant differences in the incidence of individual solicited injection site adverse events between the two treatment groups. The most commonly observed solicited injection site adverse events in both groups were injection site pain and injection site warmth. The results were consistent for all side effects. The incidence of severe solicited injection site adverse events was 3.8% (56/1469) in the DS-5670a group and 5.3% (39/735) in the Spikevax group. The most commonly observed solicited injection site adverse events were injection site warmth (21 subjects) in DS-5670a group and injection site warmth, injection site erythema, injection site pain (13 subjects each) in the Spikevax group. The incidence of solicited systemic adverse events was not different significantly between the DS-5670a group and the Spikevax group. There were no significant differences in the incidence of individual solicited systemic adverse events between the two treatment groups. The most commonly observed solicited systemic adverse events in both groups were fatigue, headache, and fever. The results were consistent for all side effects. The incidence of severe solicited systemic adverse events was 5.6% (82/1469) in the DS-5670a group and 7.2% (53/735) in the Spikevax group. The most commonly observed solicited systemic adverse event in both groups was fever (44 subjects in the DS-5670a group and 30 subjects in the Spikevax group). The incidence of unsolicited adverse events was not different significantly between the DS-5670a group and the Spikevax group. The most commonly observed unsolicited adverse events in the DS-5670a group were injection site erythema, injection site swelling, injection site induration, and fever. The results were consistent for all side effects. The incidence of severe unsolicited adverse events was 1.9% (28/1469) in the DS-5670a group and 0.4% (3/735) in the Spikevax group. The most commonly observed unsolicited adverse event in the DS-5670a group was injection site erythema (23 subjects), while in the Spikevax group, floating dizziness, nausea, joint pain, and injection site pain (1 subject each). Among them, injection site erythema (22 subjects in the DS-5670a group) and joint pain (1 subject in the Spikevax group) were considered to be related to the investigational product. No deaths were reported. The incidence of serious adverse events was 1.6% (47/3007) in the overall DS-5670a group, 1.7% (13/769) in the Comirnaty group, and 0.8% (6/735) in the Spikevax group, with no significant differences between the treatment groups. Among the serious adverse events evaluated separately for each initial vaccine, the events and incidence in at least 2 subjects in any treatment group were COVID-19 (0.1% [2/1538]) and cerebral infarction (0.1% [2/1538]) in the Comirnaty group, and diverticulitis (0.1% [2/1469]) and breast cancer (0.1% [2/1469]) in the Spikevax group. Events that occurred in at least 2 subjects who administered a booster dose of DS-5670a, regardless of the initial series, included retinal detachment, inguinal hernia, rotator cuff syndrome, shoulder tendon rupture arthropathy, ovarian cyst, lower limb fracture, and tendon rupture (each event occurred in 1 subject from the Comirnaty group and 1 subject from the Spikevax group). Hospitalization (event: hospitalization) in 1 subject from the Comirnaty group was considered to be related to the investigational product, while the other events were determined to be "not related" with the investigational product.

Non-inferiority verification part: - For the primary endpoint, the geometric mean fold rise (GMFR) of serum neutralizing activity against SARS-CoV-2 (original strain) after 4 weeks from the administration of the investigational product (Day 29), the ratio of GMFR in the DS-5670a to the active-comparator (95% CI, 97.5% CI) was 1.464 (1.152-1.861, 1.112-1.927) in Comirnaty group and 1.772 (1.383-2.270, 1.335-2.353) in Spikevax group. The lower limit of the two-sided 97.5% CI for the ratio of GMFR exceeded the non-inferiority margin of 0.67, demonstrating non-inferiority of the DS-5670a to the active-comparator regardless of the type of initial series. - For the geometric mean titer (GMT) of serum neutralizing activity against SARS-CoV-2 (original strain) after 4 weeks from the administration of the investigational product (Day 29), the ratio of GMT in the DS-5670a to the active-comparator (95% CI) was 1.414 (1.085-1.843) in the Comirnaty group and 1.896 (1.466-2.452) in the Spikevax group, indicating that the GMT after 4 weeks from administration of the investigational product was higher in the DS-5670a compared to the active-comparator regardless of the type of initial series. - For the seroconversion rate of serum neutralizing activity against SARS-CoV-2 (original strain) after 4 weeks from the administration of the investigational product (Day 29), the difference between the DS-5670a group and the active-comparator group was -1.4% (-5.9% to 5.4%) in the Comirnaty group and 2.1% (-4.4% to 11.1%) in the Spikevax group, indicating that the seroconversion rates were similar between the DS-5670a and the active-comparator regardless of the type of initial series. - For the anti-RBD IgG in serum after 4 weeks from the administration of the investigational product, the ratio of geometric mean concentration (GMC) in the DS-5670a group to the active-comparator group (95% CI) was 2.260 (1.878-2.719) in the Comirnaty group and 2.596 (2.178-3.094) in the Spikevax group, indicating that the GMC after 4 weeks from the administration of the investigational product was higher in the DS-5670a compared to the active-comparator regardless of the type of initial series. - There were no significant differences in the incidence and cumulative incidence of adverse events between the treatment groups from Day 8 to 52 weeks after the administration of the investigational product. The ratio of the incidence rate of COVID-19 between the DS-5670a group and the active-comparator group was 1.06 (0.86-1.31) in the Comirnaty group and 0.83 (0.68-1.02) in the Spikevax group. There were no significant differences in the incidence rate of COVID-19 between the treatment groups at any point.

DS-5670a 60ug or an active-comparator (Comirnaty or Spikevax) was administered as a booster dose to healthy Japanese adults and elderly subjects who had completed the initial series of an approved SARS-CoV-2 vaccine. Regardless of the type of initial series, the booster dose of DS-5670a 60ug demonstrated non-inferiority of serum neutralizing activity against SARS-CoV-2 (original strain) to the active-comparators and showed no safety concerns.

No

https://jrct.niph.go.jp/latest-detail/jRCT2071210106

Inoguchi Akihiro

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Complete

Jan. 31, 2022

Interventional

randomized controlled trial

double blind

active control

parallel assignment

prevention purpose

1)Adults aged 18 to 64 years at the time of consent, or elderly subjects aged 65 years or older at the time of consent.
2)Subjects who had received the 2nd dose of the initial series of SARS-CoV-2 vaccines (either Comirnaty or Spikevax[previously Moderna]) at least 6 months prior to signing consent.

1)Subjects who have a history of seizure or epilepsy after vaccination.
2)Subjects who have had symptoms of SARS-CoV-2 infection and been diagnosed with SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) test, SARS-CoV-2 antigen test, or SARS-CoV-2 antibody test in the past.
3)Subjects who have suggestive symptoms of SARS-CoV-2 infection (respiratory symptoms, headache, malaise, olfactory dysfunction, or taste disorder, etc.) at the time of consent.
4)Subjects who have a positive SARS-CoV-2 antigen test or SARSCoV-2 antibody test at the time of eligibility assessment.
5)Subjects who have a history of anaphylaxis or severe allergy to food, pharmaceuticals, cosmetics, vaccination, etc.

Both

Prevention of infectious disease by SARS-CoV-2

A intramuscular injection of DS-5670a (10, 30 or 60 ug) , placebo, Comirnaty, or Spikevax once in total

Efficasy: Geometric mean fold rise (GMFR) of neutralizing antibody titer against SARS-CoV-2 in blood after 4 weeks (Day 29) of treatment with the study drug
Safety: Specific adverse events (injection site and systemic) and adverse reactions, unspecified adverse events and adverse reactions, serious adverse events and adverse reactions, laboratory data, 12-lead ECG (dose escalation part only)

Efficacy:
- GMT and seroconversion rate of serum neutralizing activities against SARS-CoV-2 after 4 weeks from the administration of study drug
- GMT of serum anti-RBD IgG titers after 4 weeks from the administration of study drug
- The incidence of SARS-CoV-2 infection within 52 weeks from the administration of study drug
Safety:
- Serious adverse events
- Solicited adverse events (injection site and systemic)
- Unsolicited adverse events

+81-92-283-7701

Dec. 18, 2021

none