Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
ALX-0061 · 6 trials · 2 indications
The primary endpoint was evaluated by determining if there was a dose-response relationship between the mBICLA response rate at Week 24 and the dose administered, using the Multiple Comparison Procedure - Modelling (MCP-Mod) methodology. The existence of several candidate parametric models was assumed and multiple comparison techniques were used to choose the model(s) most likely to represent the true underlying dose-response curve. The selected model could further be used to guide the choice of adequate doses. mBICLA responders were defined as subjects who met all of the following criteria: 1. BILAG-2004 normal improvement: all A scores at Baseline improved to B, C or D, and all B scores improved to C or D. 2. No worsening in disease activity: no new BILAG-2004 A scores and ≤ 1 new increase to B. 3. No worsening of total mSLEDAI-2K score from Baseline. 4. No significant deterioration (\< 10% worsening from Baseline) in PGA. 5. No treatment failure (including the premature
ACR 20 response is defined as: * 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND * 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND * 20% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - visual analogue scale \[VAS\]) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) * C-reactive protein (CRP) level ACR20 responses were measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.
ACR50 response is defined as: * 50% improvement in TJC (68 joints) relative to Week 0 AND * 50% improvement in SJC (66 joints) relative to Week 0 AND * 50% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - VAS) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by HAQ-DI * CRP level ACR50 responses were measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.
ACR70 response is defined as: * 70% improvement in TJC (68 joints) relative to Week 0 AND * 70% improvement in SJC (66 joints) relative to Week 0 AND * 70% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - VAS) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by HAQ-DI * CRP level ACR70 responses were measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.
The ACR-N Index of Improvement is defined as the minimum of the following 3 criteria: * The percent improvement from Week 0 in TJCs * The percent improvement from Week 0 in SJCs * The median percent improvement from Week 0 for the following 5 assessments: * Subject's assessment of pain (VAS) * Subject's global assessment of disease activity (VASPHA) * Physician's global assessment of disease activity (VASPHA) * Subject's assessment of physical function as measured by the HAQ-DI * CRP level ACR-N Index of Improvement was measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.
DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln\[ESR\]) +(0.014 × VASPA) * Remission = DAS28(ESR) \< 2.6 * Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 * Moderate disease activity = 3.2 \< DAS28 ≤ 5.1 * High disease activity = DAS28 \> 5.1 Disease activity based on DAS28(ESR) was measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.
DAS28(CRP) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.36 × ln\[CRP+1\]) + (0.014 × VASPA) + 0.96 * DAS28(CRP) \< 2.6 * Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 * Moderate disease activity = 3.2 \< DAS28 ≤ 5.1 * High disease activity = DAS28 \> 5.1 Disease activity based on DAS28(CRP) was measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.
ACR 20 response is defined as: * 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND * 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND * 20% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - visual analogue scale \[VAS\]) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) * C-reactive protein (CRP) level The primary endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing ACR20 response at Week 12 were treated as non-responders.
ACR 20 response is defined as: * 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND * 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND * 20% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - visual analogue scale \[VAS\]) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) * C-reactive protein (CRP) level The primary endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing ACR20 response at Week 12 were treated as non responders.
| Arm | Type | Description |
|---|---|---|
| Placebo | PLACEBO_COMPARATOR | Two s.c. injections with placebo every 2 weeks (q2w). \*\*\* Placebo was supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to the placebo group received 2 s.c. injections q2w: Syringe A with placebo (1 mL) q2w starting at Day 1, up to and including Week 46. Syringe B with placebo (0.5 mL) q2w starting at Day 1, up to and including Week 46. |
| ALX-0061 75 mg q4w | EXPERIMENTAL | ALX-0061 75 mg every 4 weeks (q4w). \*\*\* Vobarilizumab (ALX-0061) and placebo were supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 75 mg q4w received 2 s.c. injections q2w: Syringe A with placebo (1 mL) q2w starting at Day 1, up to and including Week 46. Syringe B with ALX-0061 (0.5 mL) q4w at Day 1, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44, and syringe B with placebo (0.5 mL) q4w at Weeks 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, and 46. |
| ALX-0061 150 mg q4w | EXPERIMENTAL | ALX-0061 150 mg every 4 weeks (q4w). \*\*\* Vobarilizumab (ALX-0061) and placebo were supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 150 mg q4w received 2 s.c. injections q2w: Syringe A with ALX-0061 (1 mL) q4w at Day 1, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44, and syringe A with placebo (1 mL) q4w at Weeks 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, and 46. Syringe B with placebo (0.5 mL) q2w starting at Day 1, up to and including Week 46. |
| ALX-0061 150 mg q2w | EXPERIMENTAL | ALX-0061 150 mg every 2 weeks (q2w). \*\*\* Vobarilizumab (ALX-0061) and placebo were supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 150 mg q2w received 2 s.c. injections q2w: Syringe A with ALX-0061 (1 mL) q2w starting at Day 1, up to and including Week 46. Syringe B with placebo (0.5 mL) q2w starting at Day 1, up to and including Week 46. |
| ALX-0061 225 mg q2w | EXPERIMENTAL | ALX-0061 225 mg every 2 weeks (q2w). \*\*\* Vobarilizumab (ALX-0061) was supplied as a sterile liquid for s.c. injection at a volume of 0.5 mL and 1.0 mL in pre-filled single-use syringes. To maintain the blind, subjects randomly assigned to ALX-0061 225 mg q2w received 2 s.c. injections q2w: Syringe A with ALX-0061 (1 mL) q2w starting at Day 1, up to and including Week 46. Syringe B with ALX-0061 (0.5 mL) q2w starting at Day 1, up to and including Week 46. |
| ALX-0061 150 mg q2w (+ MTX) | EXPERIMENTAL | - |
| TCZ 162 mg q1w or q2w | ACTIVE_COMPARATOR | Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen). |
| Placebo q2w + MTX | PLACEBO_COMPARATOR | Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. |
| ALX-0061 75 mg q4w + MTX | EXPERIMENTAL | ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. |
| ALX-0061 150 mg q4w + MTX | EXPERIMENTAL | ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. |
| ALX-0061 150 mg q2w + MTX | EXPERIMENTAL | ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. |
| ALX-0061 225 mg q2w + MTX | EXPERIMENTAL | ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. |
| ALX-0061 low dose i.v. | EXPERIMENTAL | - |
| ALX-0061 high dose i.v. | EXPERIMENTAL | - |
| ALX-0061 low dose s.c. | EXPERIMENTAL | - |
| ALX-0061 middle dose s.c. | EXPERIMENTAL | - |
| ALX-0061 high dose s.c. | EXPERIMENTAL | - |
| ALX-0061 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| ALX-0061 | BIOLOGICAL | - |
| Placebo | BIOLOGICAL | - |
| Tocilizumab | BIOLOGICAL | - |
| Methotrexate | DRUG | Stable background dose of commercially available methotrexate (not provided by the Sponsor). |
Inclusion Criteria: 1. Man or woman ≥ 18 years and \< 65 years of age 2. Have a diagnosis of SLE for at least 6 months prior to screening and fulfill the 1997 American College of Rheumatology (ACR) or 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria 3. Have mo...
ALX-0061 is an investigational monoclonal antibody being developed for systemic lupus erythematosus and rheumatoid arthritis. It is currently in Phase 2 clinical development and has been studied in patients with rheumatoid arthritis in multiple clinical trials.
ALX-0061 targets the interleukin-6 receptor (IL-6R). It is designed to block this receptor, which is involved in inflammatory processes relevant to autoimmune conditions like rheumatoid arthritis and systemic lupus erythematosus.
Sanofi (ticker: SNY) is developing ALX-0061. The drug is a monoclonal antibody in the immunology therapeutic area, currently in Phase 2 clinical trials for systemic lupus erythematosus and rheumatoid arthritis.
ALX-0061 is in Phase 2 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Five clinical trials have been completed, including Phase 1 and Phase 2 studies.
ALX-0061 has been studied in five completed trials, including NCT01284569, a Phase 1 study in rheumatoid arthritis patients; NCT02101073, a Phase 1 bioavailability study in healthy volunteers; NCT02309359, a Phase 2 dose-ranging study; and NCT02518620, a Phase 2 open-label extension study. Total enrollment across these trials was 1,137 participants.
ALX-0061 is also known by its chemical name, anti-IL-6R nanobody. It is a monoclonal antibody that targets the interleukin-6 receptor and is being developed for autoimmune conditions including rheumatoid arthritis and systemic lupus erythematosus.